2012

KCE REPORT 1

DÉPIS

76B

STAGE DDU CANNCER DDU SEINN ENTRE 70 ETT 74 AN

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2012

KCE REPORT 1GOOD CLINICA

DEPIS FRANÇOISE M

76B AL PRACTICE

STAGE D

MAMBOURG, JO R

DU CAN

ROBAYS, SOPHI

NCER D

IE GERKENS

DU SEINN ENTRE 70 ETT 74 AN

www.kce.fgo

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ov.be

COLOPHOTitre:

Auteurs:

Relecture:

Experts externe

Validateurs exte

Conflits d’intérê

Layout:

Disclaimer:

Date de publica

Domaine:

MeSH:

Classification N

Langue:

ON

es:

ernes:

êt:

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NLM:

Dépi

Fran

Fran

Marc(ASBNeveVand

Philip

Aucu

Ine V

• Lereet

• Ucora

• F• Le

re

26 ap

Good

Brea

WP 8

franç

stage du cancer d

çoise Mambourg

k Hulstaert (KCE)

c Arbijn (WIV - ISBL Brummammo)en (UZ Leuven), Mdenbroucke (UCL

ppe Autier (IPRI-L

un conflit déclaré

Verhulst

es experts exteremarques ont étét n’étaient pas néne version (finaonsensus ou d’uapport scientifiquinalement, ce rape KCE reste seuecommandations

pril 2012

d Clinical Practice

st Neoplasms ; M

870 - Breast - Neo

çais, anglais

du sein entre 70 e

(KCE), Jo Robays

), Pascale Jonckh

SP), Martine Berli), Joëlle DesreuxMyriam Provost (SSaint-Luc), Geert

Lyon), Geert Page

rnes ont été coné discutées au cécessairement dale) a ensuite étun vote majoritaue et ils n’étaienpport a été appro

ul responsable ds faites aux auto

e (GCP)

Mammography ; M

oplasms

et 74 ans

s (KCE), Sophie G

heer (KCE), Nancy

ière (UCL Saint-Lx (CHU Liège), ASSMG), Hubert Tht Villeirs (UZ Gent

e (Jan Yperman Z

nsultés sur une vours des réunion

d’accord avec soté soumise aux

aire entre les valt pas nécessaireouvé à l'unanimies erreurs ou omrités publiques.

ass Screening

Gerkens (KCE)

y Thiry (KCE)

Luc), Hilde BosmAndré-Robert Grivhierens (UGent), Rt).

Ziekenhuis), Chant

version (préliminns. Ils ne sont pan contenu.

x validateurs. Laidateurs. Les va

ement tous les trté par le Conseilmissions qui po

ans (UZ Leuven)vegnée (Institut JReinhilde Van Ee

tal Van Ongeval (

naire) du rapporas co-auteurs du

a validation du ralidateurs ne sonrois d’accord avel d’administratiourraient subsiste

), Jean-Benoit BuJules Bordet), Pa

eckhoudt (WVG), A

(KU Leuven)

rt scientifique. Lu rapport scientif

rapport résulte nt pas co-auteurec son contenu. n. er de même que

urrion atrick Anne

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e 70 et 74 ans. Gté (KCE). 2012.

fédéral d’expertis

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actice 76B.

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KCE Report 176

PRÉF

6B

FACE Faire des csur l’âge. Cpersonne, uraisonnemeparfois diamLa présenteâgées de 7particulièrene présenteL’adage priEn matière logique utilscreening. clairement explique polaisser l’opipolitiquemeMême si onpour autanpeut attend

Jean-PierreDirecteur G

Dé

choix en matière dComment par exeuniquement sur uents conduisent symétralement oppoe étude qui pose 70 à 74 ans, noument vigilants surent a priori pas deimum non nocered’argumentation isée pour poser Dans le premierconsidéré comm

ourquoi les inconvinion publique ind

ent. n mobilise toutes t espérer arrêter

dre d’un organe d’

e CLOSON Général Adjoint

épistage du cancer

de soins ressembemple justifier le rn critère d’âge, mystématiquement

osés. la question de sa

us place donc à r un tel sujet. Come plainte de santéest donc ici d’autà développer, il yun diagnostic cher cas, le risque de moins importanvénients d’un dépdifférente, un lobb

les preuves scienla controverse. Navis scientifique d

r du sein

ble vite à de la disrefus de rembour

même si pour le reà des discussion

avoir s’il faut offrirnouveau sur un mme dans tout déé et qui n’étaient dtant plus importany a aussi un défi pez une personned’un résultat fauxnt qu’un résultat fpistage sont systébying intense est

ntifiques disponibNous osons néandans un tel débat.

scrimination, en prsement d’une inteste cette personnns enflammées, no

r un dépistage orsol glissant. Maisépistage organisédonc pas nécessant. particulier à relevee qui a une plaintx positif est nonfaux négatif, qui matiquement sout organisé à son

bles pour fonder unmoins espérer q

particulier lorsque tervention coûteusne est encore en ourries à partir de

rganisé du cancers il y a encore dé, on s’adresse enairement demand

er. Le clinicien este que de celle u seulement plus équivaut à loupe

us évalués. De plupropos, et il est

un avis sur la queue ce rapport ap

ces choix sont base sur le cœur à bonne forme? De

e systèmes de val

r du sein aux fem’autres raisons dn effet à des genseurs d’un tel exam

t plus coutumier dutilisée en matière

petit mais est aer un diagnostic. us, le sujet est loi(donc) aussi sen

estion, on ne peutpportera tout ce q

Raf MERTENDirecteur Gén

i

asés une

e tels leurs

mmes d’être s qui men.

de la e de aussi Cela n de sible

t pas qu’on

S néral

ii

RÉSUUMÉ

Déépistage du cancer

ICdnasLddmasLedecLfeaLqspdstrEqdle

r du sein

NTRODUCCe travail fait partdu rapport: «Dépisn°11). Il concerneaux femmes âgésymptôme évocateLe dépistage du cdes bénéfices etdépistage du canmorbidité liées à allègement des tstades métastatiquLes risques princieffet, un résultatdiagnostic) suivi dest la durée par laclinique) ont des cLes résultats fauemmes en bonanxiogènes voire iLe sur-diagnosticqui n’auraient jams’accroit au fur et population dépistdiagnostic. Vu qu’se développer, laraités. Enfin, le dépistageque ne le ferait udevient «malade de décours de sa v

CTION tie d’un projet plustage du cancer

e plus particulièremes de 70 à 74eur, ni facteur de cancer du sein est des risques. Lcer du sein sontla maladie. La di

traitements, soit ues de la maladiepaux liés au dépfaussement pos

’un traitement et laquelle le diagnosconséquences surssement positifs ne santé dans invasifs (biopsies)peut être défini cais été perçus clin à mesure de la ée. Le sur-traiteil est actuellemen

a très grande ma

e met les cancersun diagnostic clindu cancer» et reçovie.

us large ayant podu sein», publié ment l’extension ans qui ne présrisque particulier.

st un processus cLes principaux bt la diminution deiminution de morune diminution d

e. pistage concernensitif, un diagnost’avance au diagnstic par dépistager la qualité de vie.

ont pour conséun circuit d’ex

). comme la détectiniquement en l’abdiminution de l’e

ement est une cnt impossible de pajorité des cance

s en évidence deunique. Ceci imploit des traitements

KCE Report 1

ur objet la mise àen 2005 (rapportdu dépistage org

sentent par ailleu

complexe qui combénéfices attendue la mortalité et rbidité implique sodes récidives ou

nt la qualité de vitic excédentaire ostic (ou lead tim

e précède le diagn

équence d’inclurexamens diagnost

on de cas de cabsence de dépistaespérance de vie conséquence duprédire si un cancers diagnostiqués

ux ou trois ans plique que la perss invasifs plus tôt

176B

à jour KCE anisé

urs ni

mporte us du de la oit un u des

e. En (sur-

e, qui nostic

e des tiques

ncers age. Il de la sur-

cer va sont

us tôt sonne

dans

KCE Report 176

QUESTIOCe rapport invorganisé du canSi la réponse àpose: que répodépistage?

MÉTHODL’étude des bélittérature effectrevue a inclus Français de janL’évaluation durevue des étudNHS EED et EAllemand, NéerAfin de quantifimodèle a été nécessité de r(1950-10/2011)dépistage et lemaximum de doEnfin, des recobase des élérecommandatiod’intérêts n’a ét

6B

ONS POSÉvestigue la questncer du sein aux fà cette question

ondre à la personn

DOLOGIE énéfices cliniquestuée dans OVID Mles articles publ

nvier 2004 à avril 2 rapport bénéficedes de modélisat

Econlit. Cette revurlandais et Françaier le rapport bénconstruit dans cechercher dans ) les études relative traitement du onnées belges utiommandations deéments de pre

ons a été effectuété signalé.

ES ion suivante: faufemmes âgées deest négative, unene de cette tranch

s du dépistage seMedline, EMBASEiés en Anglais, A2011. s-risques de ce dtion recherchées ue a inclus les arais de janvier 2000néfices-risques dace but. La constMedline, Embaseves à la qualité dcancer du sein.

ilisables. e bonne pratiqueeuve obtenus.ée par les expert

Dé

ut-il étendre le dée 70 à 74 ans? e question subsidhe d’âge qui dem

e base sur une rE, CDSR et DARAllemand, Néerla

épistage se basedans Medline, E

rticles publiés en 0 à septembre 20ans le contexte btruction de ce me, HTA EED et Pe vie pendant et . Le modèle con

e ont été rédigéeUne révision d

ts externes. Aucu

épistage du cancer

épistage

diaire se ande un

evue de RE. Cette

ndais et

sur une Embase, Anglais,

011. elge, un

modèle a Psycinfo après le ntient le

es sur la desdites

un conflit

RMLm•

•

Dnla

MOepbvfotodtrcDrédma

r du sein

RÉSULTATMortalité Les résultats desmettre en évidenc Le dépistage

période de subénéficié d’un

Cette diminutdépistage. Il l’espérance d70 ans et de 1

Dans l’interprétationombre de participa mortalité n’a pu

Morbidité Outre le gain en aest de permettre pour objectif de mbelges dont nousvalider cette asseont état de 58% dotales dans les stdes bénéficiaires raitement par radchimiothérapie néoD’autre part, les eécidives ni l’évolu

donc impossible dmorbidité sur cetteaux métastases es

TS ISSUS D

s différents essaise les faits suivantentraîne une dim

uivi de 13 ans chen dépistage tous letion de mortalité s

convient donc e vie moyenne d13 ans à 74 ans (don des études intepantes âgées de 7être statistiqueme

années de vie, le pdes traitements mmettre en évidens disposons acturtion. Les donnéede chirurgie constades les moins ade la chirurgie

diothérapie, 38% do-adjuvante et 41essais contrôlés rution vers les stad’infirmer ou de coe base. Par contrst inclue dans le m

DE LA LITT

s contrôlés randots: minution de mortez les femmes dees deux ans. se manifeste entr

de la mettre e ce groupe d’âgdonnées belges dernationales, il fau70 à 74 ans; consent démontré pou

principal avantagemoins agressifs, vnce des petites tuellement ne noues les plus récenservatrice versus avancés (Stades conservatrice reçd’entre elles reço% un traitement h

randomisés n’ont des métastatiqueonfirmer l’hypothère, la perte de qumodèle (voir ci-de

TÉRATURE

omisés permette

talité de 23% sue plus de 50 ans

re 4 et 7 ans apren perspective

ge qui est de 16 ade 2009). ut tenir compte duséquemment, l’effeur celles-ci.

e attendu du dépivu que le dépistaumeurs. Les donus permettent pates (rapport KCE38% de mastectoI and II). Près deçoivent égalemen

oivent un traitemehormonal. quantifié ni le tau

es de la maladie. èse d’une réductioualité de vie impuessous).

iii

E

nt de

r une ayant

rès le avec

ans à

u petit et sur

stage age a nnées as de 150)

omies e 90% nt un

ent de

ux de Il est

on de utable

iv

ÉTUDESLes principalesCISNET (Cancmodèles avaiedépistage par mla mortalité due2000, et ils utConsortium. Les résultats de9 à 22 ans parla méthodologscientifique. Ces modèles ncar il est imposspécifique a do

UN MODÈBELGIQUMéthodologieLe modèle conpar cycles annplus de 70 ansl’autre où les feparticipation et les cancers d’inla tranche d’âgeLe dépistage a précoce (I et métastatique) qles cancers dépmême temps qD’autre part, nqualité de vie dElle ne tient pa

DE MODÉ études de modé

cer Intervention aent pour objectimammographie ete au cancer du tilisent les donné

e ces modèles indr 1.000 femmes dgie CISNET son

ne sont pas adaptssible d’y inclure nc été construit.

ÈLE DE COUE e struit pour ce rapuels. Il compare s, l’une sans inviemmes continuenla répartition des

ntervalle sont conse 50-69 ans. pour objectif de m

II) afin d’évitequi est incurable. pistés, la proportioque la proportionous avons émis

dépendent de l’âgas compte du fait

ÉLISATIONélisation ont été réand Surveillance if d’évaluer la t du traitement adsein observée auées issues du B

diquent un gain edépistées. D’autrent également d

tables en tant queles données belg

OHORTE P

pport est un modèdeux cohortes th

itation au dépistant à être invitées s cancers détectéssidérés comme é

mettre en évidencer l’évolution veCe «stage-shift»

on des stades prén des stades aval’hypothèse selon

ge de la patiente eque le pronostic d

Dé

éalisées au sein dModeling Netwocontribution relajuvant sur la réduux Etats-Unis de

Breast Cancer Sc

n années de vie aes modèles n’utilisdécrits dans le

e tels à la situatioges. Un nouveau

POUR LA

èle de cohorte quhéoriques de femage (situation actau dépistage. Le s par le dépistagetant les mêmes q

ce les tumeurs à uers le stade IV implique que pa

écoces (I, II) augmancés (II et IV) dn laquelle la survet du stade de la des cancers déte

épistage du cancer

du projet rk). Ces

ative du uction de

1975 à creening

allant de sant pas

rapport

on belge modèle

ui évolue mmes de uelle) et taux de

e versus que dans

un stade V (stade

rmi tous mente en diminue. vie et la tumeur.

ectés par

le(cp

PCl’disnIndooLé

MLpsdtabLd•

•

Pc

r du sein

e dépistage estcancers d’interva

participantes).

Paramètres Ce modèle explespérance de v

données du regisssues du progranécessaire pour ntermutualiste, AIdu stade (Registreont été privilégiéesopportuniste aprèsLa durée de l’avanété estimées au dé

Mesure de la qLes données sur proviennent de la santé est l’EQ-5descriptions ont éariffs»). Nous nebelge. Les variations de dans le modèles s La perte de

faussement p Pour les patie

le diagnostic (estimée à 16Pendant les a6% pour les pour les stade

Plusieurs limitatiochiffres avec préca

meilleur que celalle et cancers

loite au maximuie moyenne des

stre du cancer (Camme de dépis

infirmer un diaIM/IMA) et les doe du Cancer). Less car elles sont pls 70 ans y est monce au diagnostic épart de l’analyse

ualité de vie la qualité de vielittérature. L’instr

5D (European été valorisées pare disposons pas

la qualité de vie dsont les suivantesqualité de vie coositif est estimée

entes cancéreuse(quel que soit le t% pour les stade

années suivantes,stades I, II, III. Ces IV. ons de cette appaution

lui des cancers survenant che

um les données femmes selon Communauté Flastage actuel (50agnostic faussem

onnées de survie données de la Clus complètes et poins fréquent que

et le pourcentagee de la littérature.

e pendant le déprument utilisé pouQuality of Life-r la population géde données rela

des femmes de p: onsécutive à un à 16% pendant 4s et pendant la ptraitement) la pertes I, II, III et à 18 la perte de qualit

Cette perte demeu

proche nous oblig

KCE Report 1

détectés cliniqueez les femmes

s belges, à saleur âge (2009)

amande), les don0-69 ans), le tment positif (Agà cinq ans en fonommunauté Flamparce que le dépidans le reste du e de sur-diagnost

istage et le traiteur décrire les éta-5 Dimensions); énérale anglaise atives à la popu

lus de 70 ans util

résultat de dépi45 jours. remière année qute de qualité de v8% pour les stadeté de vie est estimure stationnaire (

gent à interpréte

176B

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avoir : ), les nnées emps

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mande stage pays.

tic ont

ement ats de

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lisées

stage

ui suit ie est es IV. mée à (18%)

r ces

KCE Report 176

Résultats Le scénario dpermettrait d’évreprésente uned’années de vieEtant donné qules discussionsune analyse dcomprend un scLe scenario pe20%, d’un taux vie de 0,19 perdrésultats). La actuellement daa été appliquéd’estimer un ga1000 femmes circonstances, aboutir à une peLe scenario opd’un taux de fa0,13 perdurant la distribution dépistage orgapermet d’estimepour 1000 femnécessaire d’invpour gagner un

6B

de base montre viter 1,3 décès poe réduction de 2e sauvées est estiu’il existe une incs dans le rapport de sensibilité ducénario pessimistessimiste fait l’hyde faux positifs d

durant pendant 54distribution des

ans le cadre du dée au groupe dain de 8,7 annéeparticipant au déau demeurant t

erte en terme de qtimiste fait l’hypotux positifs de 2%pendant 36 jourspar stades obs

anisé aux Pays-Ber un gain de 17mmes participant viter 67 femmes à QALY.

que le dépistagour 1000 femmes

21% des décès. imé à 13,1 et le gcertitude importanscientifique) au s

u modèle a été te et un scénario oypothèse d’un exde 10%, entrainan4 jours (temps nécancers dépisté

dépistage organisdépisté. Ce scénes de vie et une épistage. Ceci sigtout à fait réalistqualité de vie. thèse d’un excéd

%, entrainant une ps. Ce scénario apservée actuellemBas (70-74 ans),0 années de vie

au dépistage. à participer au dé

Dé

ge entre 70 et s qui y participentGlobalement, le ain en QALY à 3,nte (pour les détasujet des ces estim

réalisée. Cette optimiste. xcédent de diagnnt une perte de quécessaire pour infiés par stades oé en Flandre (50-nario pessimiste perte de 3,1 QA

gnifie que dans ctes, le dépistage

ent de diagnosticperte de qualité dpplique au groupement dans le ca). Ce scénario oet un gain de 16,Ceci signifie qu’

épistage pendant c

épistage du cancer

74 ans t, ce qui nombre

9. ails, voir mations, analyse

ostic de ualité de irmer les

observée -69 ans)

permet ALY pour certaines e puisse

c de 3%, de vie de e dépisté adre du optimiste ,3 QALY ’il serait cinq ans

CLppql’ahpbgd7

r du sein

CONCLUSLe dépistage estpopulation en évitprolonger le dépisquelques années influence d’un dé

aléatoire (niveau dhypothèses raisonperte en terme debalance bénéficesglobale de bien-êd’étendre le dépis70 à 74 ans.

ION t organisé dans ant notamment dtage jusqu’à l’âgede vie pour un

épistage organisé de preuve très fainnables, cette intee qualité de vie. Ds-risques de ce dêtre de la populstage organisé du

le but d’améliores décès prématu

e de 74 ans devracertain nombre dsur la qualité de ble car basé sur uervention pourrai

Dans ces conditiondépistage pencheation. Il n’est do

u cancer du sein a

rer le bien-être durés. Il est certain

ait permettre de gade femmes. Toutvie est nettemenun modèle). Selot même aboutir àns, il se pourrait qe du côté d’une onc pas recommaux femmes âgée

v

de la n que agner tefois, t plus n des à une que la perte

mandé es de

vi

RECO

a Le KCE re

OMMAND

este seul responsab

DATIONS

ble des recommand

Dé

Sa

• L’invitorgan

• Si unedépistdes in

• Toute de qul’enregorientexigen

• Afin dil impodesso

ations faites aux au

épistage du cancer

tation systématiisé du cancer du

e personne de tage, il importe q

nconvénients pot

mammographiealité, dont notamgistrement et leront la personnnces de qualité.

de minimiser le riorte que le taux

ous du seuil défin

utorités publiques

r du sein

ique des femmeu sein n’est pas r

plus de 70 ans que le médecin vtentiels de celle-

e de dépistage dmment : le contr’optimisation dne qui demande

isque de perte dde rappel après

ni par les critères

es âgées de 70 recommandée.

demande une veille à ce qu’elleci.

oit répondre auxrôle de la qualitéu taux de rap

e un dépistage v

e qualité de vie mammographies européens (<5%

à 74 ans à par

mammographie e soit bien inform

x exigences euroé des installationpel. C’est pour

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KCE Report 1

rticiper au dépis

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KCE Report 176

TABL

6

LE OF COONTENTLILILI

1.2.3.3.3.

4.4.

4.

4.

5.6.

S

TS ST OF FIGURESST OF TABLES .ST OF ABBREVI

SYNTHÈSCONTEXTQUESTIODESCRIPT

1. APPROCH2. APPROCH

3.2.1. O3.2.2. O3.2.3. FMÉTHODO

1. ESTIMATI4.1.1. D4.1.2. A

2. ESTIMATI4.2.1. D

3. APPROCH4.3.1. M4.3.2. D4.3.3. H4.3.4. A4.3.5. ARÉSULTADISCUSS

Screening Breast C

S .......................................................IATIONS .............

SE ........................TE ........................NS POSÉES .......TION DE LA PROHE INTUITIVE .....HE ÉPIDÉMIOLOObjectif à court terObjectif ultime .......Faux positifs et diaOLOGIE ..............ION DES BÉNÉF

Diminution de la mAmélioration de la ION DES INCONV

Diminution de la quHE PAR MODÉLIMesures de la quaDescription du modHypothèses de basAlimentation du moAnalyse de sensibATS ......................ION .....................

Cancer

............................

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............................OBLÉMATIQUE .............................GIQUE ...............

rme ..................................................agnostics excéden............................ICES DU DÉPIST

mortalité ................qualité de vie des

VÉNIENTS DU Dualité de vie des pSATION ..............

alité de la vie ........dèle ....................se ........................odèle ...................ilité ..............................................................................

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TAGE ...............................................s patientes ...........ÉPISTAGE ..........participantes ........................................................................................................................................................................................................................................

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6.6.

7.7.7.7.8.

1.1.1.1.1.1.2.2.

2.

S

1. AJOUTER2. AJOUTER

6.2.1. T6.2.2. F6.2.3. ECONCLUS

1. FAUT-IL P2. QUE REP3. MESSAGE

RÉFÉREN

SCIENTIFINTRODU

1. CONTEXT2. SCOPE O3. BREAST C4. CLINICAL5. SCIENTIF

LITERATU1. REVIEW O

2.1.1. M2.1.2. D2.1.3. D2.1.4. S2.1.5. K2.1.6. C

2. REVIEW O2.2.1. L2.2.2. S

Screening Breast C

R DES ANNÉES ÀR DE LA (QUALITTraitements moinsFaux positifs .........Excès de diagnostSIONS .................PROLONGER LE ONDRE A LA PEE CLÉ ..................NCES ...................

FIC REPORT ........CTION ................

T OF THIS REPOOF THIS REPORTCANCER SCREE QUESTIONS .....

FIC APPROACH ..URE REVIEWS ...OF CLINICAL STUMethodology .........Description of screDescription of screScreening conditioKey data ...............Conclusion ............OF MODELING SLiterature search sSelection criteria ...

Cancer

À LA VIE ? ...........É DE) VIE AUX A

s agressifs? .....................................tics et de traiteme............................DÉPISTAGE JUS

ERSONNE QUI DE........................................................

............................

............................RT ......................

T ...........................ENING IN BELGIU....................................................................................UDIES .............................................

eening benefit ......eening harms .......ons ...............................................................................

STUDIES ..............strategy ...........................................

............................ANNÉES ? ...................................................................

ents ...................................................SQU’À L’ÂGE DEEMANDE UN DEP........................................................

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KCE Report 176

6

2.

3.3.3.3.

3.3.4.4.4.4.4.4.4.4.

S

2.2.3. Q2.2.4. S2.2.5. C

3. REVIEW O2.3.1. M2.3.2. R2.3.3. DDECISION

1. DATA SOU2. MODEL D3. DESCRIPT

3.3.1. A3.3.2. B3.3.3. P3.3.4. P3.3.5. R3.3.6. S3.3.7. S3.3.8. Q

4. RESULTS5. DISCUSS

ANSWER 1. BREAST C2. DELAY BE3. OVERALL4. MORBIDIT5. FALSE PO6. ADDITION7. OVER-DIA

Screening Breast C

Quantity of researcSelected studies ...Conclusion ............OF QUALITY OFMethods ................Results .................Discussion ............N ANALYSIS .......URCES ...............

DESCRIPTION .....TION OF THE PA

Age specific overaBreast cancer incidParticipation rate ..Proportion of screeRecall rate ............Stage distribution aStage specific relaQALY ....................S ...........................ION .....................TO CLINICAL Q

CANCER RELATEETWEEN THE SCL MORTALITY .....TY ........................OSITIVE OR FALSNAL DIAGNOSTICAGNOSIS AND O

Cancer

ch available .................................................................LIFE STUDIES ...........................................................................................................................................................................ARAMETERS ......all survival ............dence ..............................................en detected breas............................and stage shift ....

ative survival ............................................................................................

QUESTIONS .........ED MORTALITY .

CREENING AND T........................................................SE NEGATIVE RC TESTS .............

OVER-TREATMEN

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............................st cancers ............................................................................................................................................................................................................................................THE MORTALITY........................................................ESULTS ..........................................

NT ........................

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4

LIST OF F

LIST OF T

FIGURES

TABLES

4.5.

FiFiFiFi

TaTaTaTawoTaTaTaTaTapaTaTaTa

S

8. WHAT ATREFEREN

gure 2.1: Health sgure 2.2: Percentgure 3.1: Compargure 3.2: Compar

able 2.1: Data issuable 2.2: Selectionable 2.3: Modelingable 2.4: results omen screened foable 2.5: Article seable 2.6: Health stable 2.7: Descriptable 2.8: Descriptable 3.1: Stage diarticipants, age 50able 3.2: Parametable 3.3 Modelingable 3.4 Modeling

Screening Breast C

TTITUDE SHOULDNCES ...................

states for which uttage change in utirison of the two cortments in the two

ued from clinical ln criteria ..............g studies excludedof the different m

or the different moelection criteria ....tates descriptionsion of a “false posion of the selectedistribution among 0-69, Flemish screters used in the m results: baseline results: sensitivit

Cancer

D BE RECOMME............................

tilities are neededlities ....................

ohorts with and wo cohorts and the t

iterature review ..............................d after full-text assmodels in terms oodels ................................................s for the study of Lsitive” state (Gerad utilities .............screen detected

eening program 2model ....................

, worst and best cty analysis. ..........

NDED FOR WOM............................

d (reflection proce............................ithout a screeningtransitions betwee

............................

............................sessment ............of mortality reduc........................................................

Lidgren et al. ........rd et al)83 .........................................breast cancers, i001-2006. .......................................

case scenario. .................................

MEN IN CASE OF............................

ss) ..................................................g program ............en them ..............

............................

............................

............................ction and years o............................................................................................................................................nterval cancers a................................................................................................................

KCE Report

F SELF REFERRA............................

............................

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............................of life gained per............................................................................................................................................

and cancers amon................................................................................................................

t 176

AL?61 .... 62

..................

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.............r 1000 .................................................................ng non ....................................................

KCE Report 176

LIST OF A

6

ABBREVIAATIONS ABCPCCCIDCDEBCAHBCDNCIIMINICKCMMNINBNBNHNHNCQAQoRCRR

S

BBREVIATION PG CRT I CIS ET CSC HRQ CR NETB ISNET

MA/AIM NAMI/RIZIV CER CE ST -A IS BSS BCSP HS HS EED CI ALY oL CT R

Screening Breast C

DEFINITION Clinical PracticCochrane CenConfidence IntDuctal CarcinoData ExtractioBreast CancerAgency for HeBelgian CanceDutch NationaCancer InterveIntermutualistiNational InstituIncremental coBelgian HealthMean Sojourn Meta-analysisNational InstituCanadian NatiNorwegian BreNational HealtNHS EconomiNational CancQuality AdjusteQuality of LifeRandomized CRelative Risk

Cancer

ce Guideline ntral Register of Cterval oma in situ on Table r Surveillance Con

ealth Care Researer Registry al Evaluation Teamention and Surveic Agency ute for Health andost-effectiveness rhcare Knowledge

Time

ute for Statistics ional Breast Canceast Cancer Screeth Service (UK) c Evaluation Data

cer Institute (USA)ed Life Year

Controlled Trial

Controlled Trials

nsortium (USA) rch and Quality

m for Breast cancellance Modelling N

d Disability Insuranratio Centre

cer Screening Stuening Programme

abase )

er screening Network

nce

dy es

5

6

SESRSTTTUKUSUS

S

EER R T TO K SA SPSTF

Screening Breast C

Surveillance, ESystematic ReSojourn TimeTime-trade-offUnited KingdoUnites States US Preventive

Cancer

Epidemiology andeview

f om of America

e Services Task F

d End Results (US

orce

SA)

KCE Reportt 176

KCE Report 176

SYNT

6

THÈSE

SScreening Breast C

1Lradd4radral’soCl’SpSdaa

2Ll’àLla

Cancer

1. CONTEXLe KCE a déjà puapport de base

dépistage du cancde risque. Le dépi40-49 ans a fait l’oapport (rapport

dépistage systémapport (rapport 1indentification de

sein. Le rapport organisé du canceCette question esaugmentation rég

Si la plupart desprolongation, les Seuls quatre Etatd’âge des 70-74 autres pays insisteavec elles la prise

2. QUESTILe dépistage orgaâge de 74 ans? S

à la personne qui dLa première questa seconde, les pre

XTE blié trois rapportspublié en 2005

cer du sein en géstage du cancer d

objet d’une mise àN° 129 du KCEatique des femm

172 du KCE), pues femmes expos

actuel pose la er du sein aux femst régulièrement gulière de l’espérs groupes actifs autorités publiquts membres de (la France, les Pent sur la nécesside décision.

IONS POSÉanisé du cancer Si la réponse à cedemande ce dépition concerne plusestataires de soin

s sur le dépistage(rapport N°11 d

énéral, dans la podu sein des femmà jour partielle pubE), le KCE ne

mes de moins de ublié en 2012, a sées à un risquequestion de l’ex

mmes âgées de 70adressée aux po

rance de vie de ldans le dépista

ues font preuve dl’Union européen

Pays-Bas, l’Espagté d’informer les f

ÉES du sein devrait-il

ette question est nstage? s spécifiquement

ns.

du cancer du seu KCE) concern

opulation sans facmes de la tranche bliée en 2010. Darecommandait pa50 ans. Le troisposé le problèm

e accru de cancextension du dépi0 à 74 ans oliticiens en raisoa population fémage demandent de moins d’unannne ciblent la tragne et la Suède)1

femmes et de par

être prolongé junégative, que répo

les pouvoirs publ

7

in. Le ait le

cteurs d’âge ns ce as le sième

me de er du stage

on de inine. cette imité.

anche . Les

rtager

squ’à ondre

lics et

8

3. DESC3.1. ApprocDe façon intuitgénéralement edémontrée par aux Etats-Unis est une bonne diagnostiquer utemps. L’enthod’entre eux le impératif moral3

Cette attitude précoce des cirréalistes de ltéléphoniques psein et le bénrépondantes cprogressive unforme curable ecancer du sein précoce, il grafemmes estimacancers mortelsSchwartz a soupeut détecter ddes répondantefaire de tort à uLe corps médimanière adéqusur le taux del’objectif final dcliniciens parais(faux négatif) q

RIPTION Dhe intuitive tive, le dépistageenthousiastes à l

Schwartz au déa révélé que 87

idée. Trois quart dun cancer à un susiasme des répdépistage n’éta

3. générale que no

cancers sauve dela part des femmpour évaluer coméfice du dépistagconsidérait le c

niforme et croyaitet silencieuse. Enn'est pas détecté

andit, se propageaient que les cancs) sont liés à un éuligné que 94% dedes cancers qui nes sont persuadéne personne qui ncal lui-même n’aate. C’est ainsi qu cancers diagnos

du dépistage est ssent plus sensibu’aux risques liés

DE LA PRO

e du cancer fait l’égard du dépista

ébut du 21e siècle% des adultes codes personnes intstade précoce sa

pondants était si it pas une décis

ous pouvons réses vies” peut avmes. Silverman ment les femmesge par mammogcancer du sein t que tous les can résumé, ces femé par une mammoe et tue. Fortescers avancés (et séchec au niveau des femmes ne savne vont jamais p

ées du fait que lan'a pas de cancerappréhende pas ue de nombreux cstiqués (objectif de diminuer la m

bilisés au risque d aux résultats fau

S

OBLÉMATIQ

sens. Les médage. Cette attitude2. Une enquête onsidéraient que terrogées déclaraauve la vie la plufort que pour la sion à prendre m

sumer ainsi “la dvoir suscité des a réalisé des in considèrent le caraphie4. La majo

comme une ancers débutent mmes pensaient qographie et traité ds de ces croyansans doute la pluu dépistage précovent pas que le dé

progresser. De plua mammographie r du sein5. toujours le dépiscliniciens restent fintermédiaire), al

mortalité. D’autre de méconnaître unssement positifs.

Screening Breast C

QUE

ias sont de a été réalisée dépister

aient que upart du majorité mais un

détection attentes terviews ancer du orité des

maladie par une que si le de façon ces, les part des oce. épistage us, 92% ne peut

stage de focalisés lors que part, les n cancer

3LBtrLc7Nmred7p7

C

1

2

3

4

Rd

Cancer

3.2. ApprocheLe cancer du seBelgique, 10.849 crois quarts des caL’âge moyen au cancer du sein est70 à 75 ans6. Néanmoins, la pamortalité totale diffesponsable de 18

de 13% dans le g74 ans (Rapport pour les femmes â7% pour le groupe

Caractéristiques fo

. Le dépistagContrairemeune plainte dépistage es

2. Le dépistage la maladie.

3. Le dépistage liée à la mala

4. Le principe “pce qui concer

Rappelons que pde 990 sont indem

épidémiologiqin est le cancer cancers du sein oancers du sein somoment du diag

t de 370,7/100.00

rt relative de la mfère en fonction d8% des décès chroupe de 60 à 64N°11 du KCE). Eâgées de 50 à 54

e des 70 à 74 ans

ondamentales d’u

e s’adresse à ent au patient qu

ou d’un symptôst présumée inde

a pour objectif à

a pour objectif udie.

primum non nocerne le dépistage.

pour mille femmemnes du cancer

que le plus fréquen

ont été diagnostiqont diagnostiqués gnostic est de 6200 dans le groupe

mortalité due au ce l’âge. En 1999,

hez les femmes â4 ans et de 6% dEn 2006, cette pr4, 12% pour le gret 5% pour le gro

un dépistage:

des personneui consulte son môme, la personnemne de la malad

à court terme de c

ultime de diminue

re” est particulière

es dépistées entdu sein.

KCE Report

t chez la femmequés en 2008. Pluaprès l’âge de 502 ans. L’incidencdes femmes âgé

cancer du sein da le cancer du sein

âgées de 50 à 54ans le groupe deroportion était de roupe de 60 à 64oupe des 75 à 79

es en bonne médecin en raiso

ne qui participe die recherchée.

confirmer l’absenc

r la mortalité/mor

ement d’applicatio

tre 70 et 74 ans,

t 176

e. En us de 0 ans. ce du es de

ans la n était 4 ans, e 70 à 14%

4 ans, ans6.

santé on d’ à un

ce de

rbidité

on en

plus

KCE Report 176

3.2.1. ObjectLe dépistage apersonne quid’innocence” enqui consulte soconstaté quelqL’objectif du msituations sont diagnostique, leune étiologie àdépistage, le mindispensables.dépistage pour sein. Le formation dauprès de macontre-intuitif po3.2.2. ObjectDiagnostiquer développent etdépistage du cala mortalité spéLe fait que la tpeu avancées étape intermédmais qui n’est pOn peut égalemorbidité liée àinvasifs (masteévitant une part

6

tif à court terme a pour objectif d

participe au dn ce qui concerneon médecin parceque chose d’inh

médecin et les modiamétralement o

e médecin a le de la plainte ou au

médecin a le dev. Ceci afin de minr les 996 femmes

des médecins étlades, ce changeour un clinicien. tif ultime les cancers à t essaiment (méancer. C’est ainsi écifique à la malatechnologie utiliséet donc potenti

iaire dans ce procpas suffisante7. ement émettre l’à la maladie, en pectomies partielletie des évolutions

e confirmer l’absépistage bénéfice le cancer du see qu’elle a une pabituel, devientoyens à mettre eopposés. Dans leevoir de tout mett symptôme. A l’inoir de pratiquer unimiser les risque (/1.000) qui sont

tant essentiellemement de point

un stade précoétastases) est l’h

que l’on attend dadie et conséquemée permette de dellement curablecessus. Il s’agit d

’hypothèse que permettant l’utilisas plutôt que mas vers les stades m

S

sence de la malacie de la “présin. A l’inverse, la

plainte ou parce q“suspecte” de m

en œuvre dans ce cas d’une mise re en œuvre pournverse, dans le cuniquement les e

es et les inconvént indemnes du ca

ent effectuée ende vue est franc

oce avant qu’ils hypothèse fondadu dépistage qu’il mment la mortalitdiagnostiquer deses ne représente’une condition né

le dépistage rédtion de traitementstectomies totalesmétastatiques.

Screening Breast C

adie. La somption patiente

qu’elle a maladie.

ces deux au point r trouver cadre du examens nients du ancer du

n hôpital chement

ne se trice du diminue

té totale. s lésions e qu’une cessaire

duise la ts moins s) et en

3AlaacaLddpcPledccqppénC(vsd

Cancer

3.2.3. Faux posAvant d’instaurer ua balance avantaavantages. Pour contrebalancer la aux risques induitsLes résultats ditsdehors de la présedépistage du cancpositifs créent decomplémentaires. Plus encore que lee risque majeur diagnostic excédecancer dont l’évocliniquement en l’aque le cancer espersonne est faibpopulation. Très évoluent tellemenn'altèreront pas la Ce rapport a pourvoir Figure 1) de

s’assurer que les de qualité de vie.

sitifs et diagnostiun dépistage orgaages/inconvénience faire, l’ampleperte de qualité ds par le dépistages: “faux-positifs” ence d’un cancer)cer du sein les ple hauts niveaux

es faux–positifs, ldu dépistage de

entaire peut se déolution est telle absence de dépisst d’évolution lenble. Ce risque epeu de femmes

nt lentement quesanté9.

r objectif de quantce dépistage afin bénéfices l'empor

ics excédentaireanisé, il est nécesnts du dépistage eur de la diminude vie consécutivee.

(suspicion de l) sont les effets nus fréquents. Ces

x d'anxiété et so

e risque de diagns femmes âgées

éfinir comme le faqu’il ne se se

stage8. Ce risque nte et que l’espest particulièreme

savent en effet e même s'ils ne

tifier les avantagede pouvoir les m

rtent largement su

es ssaire de s’assure

penche du côtéution de mortalitée aux inconvénie

ésion cancéreuségatifs indésirables résultats fausseont suivis d’exa

nostic excédentairs de 70 à 74 anait de diagnostiqurait jamais manest d’autant plus

pérance de vie dent méconnu da

que certains cae sont pas traité

es et les inconvénmettre en perspect

ur les risques de

9

er que é des é doit nts et

se en es du

ement mens

re est s. Le er un ifesté élevé de la ns la ncers és ils

nients tive et perte

10

Figure 1 mise

 

 

Dépistmammo

en perspective d

tage par ographie

des avantages et

Normal

Anormal

S

t des inconvénie

Faux-néga

Résultat +

Faux-pos

Résultat -

Screening Breast C

nts potentiels du

atif

+

sitif

Réin

Ré

Ex

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Ca

in

Cancer

u dépistage.

éassurance nadéquate

éassurance

xamens compléme

ncer asif

ancer

n situ

Diagnostic r

entaires

Traitement précoce

Traitement précoce 

retardé

Diminutde morta

Surtrait

KCE Report

tion alité

tement

t 176

KCE Report 176

4. MÉTHNous avons recdans la littératudonnées nationsuivant les prodans le chapitre

4.1. Estimat4.1.1. DiminuLes principalessein, sont issueessais, on peut1. Le dépista

période debénéficié d

2. Cette diminans après l’espérancede ce grou(données b

Les données ppeuvent donneun seul essai rades femmes âparticipant à cepouvoir mettremortalité. De pl

6

ODOLOGIcherché des élémure clinique, dansnales et internatiocédures en viguee 2 du rapport scie

tion des bénéfiution de la mortas données probanes de huit essaist retenir deux consage entraîne une e suivi de 13 ans d’un dépistage tounution de mortalitle dépistage. Il c

e de vie de la popupe d’âge est de belges de 2009). probantes issues r une réponse coandomisé, l’étude

âgées de 70 à 7et essai était trop f en évidence uus cette étude éta

E ments de réponses les études de

onales. Ces recheeur au KCE. Ellesentifique.

ces du dépistaalité ntes relatives au s contrôlés randostats principaux:diminution de m

pour les femmes us les deux ans. é se manifeste prconvient de la mepulation-cible. L’es

16 ans à 70 ans

de ces essais cmplète à notre qu

e suédoise dite de74 ans et le nofaible (10.000 poun effet statistiquait entachée de bi

S

aux questions prmodélisation et d

erches ont été mes sont décrites en

age

dépistage du caomisés. Sur base

mortalité de 23% de plus de 50 an

rincipalement entrettre en perspectispérance de vie ms et de 13 ans à

contrôlés randomuestion de base. Ees “Two County”, mbre de septuagur les deux group

uement significatifiais méthodologiq

Screening Breast C

récitées, dans les enées en n détails

ancer du e de ces

sur une ns ayant

re 4 et 7 ive avec

moyenne à 74 ans

misés ne En effet, a inclus

génaires es) pour f sur la ues.

4LpmlecLl’immaLp(dIIétrh

44Lp1

2

Cancer

4.1.2. AmélioraLe dépistage ayapetite taille, un demoins agressifs. Nes données factucette attente. Les essais contrôévolution vers lempossible d’infirmmorbidité sur cetteaux métastases esLes données bepermettent pas derapport KCE 150)

de mastectomies I). Près de 90% dégalement un traitraitement de chhormonal.

4.2. Estimation4.2.1. DiminutioLe dépistage provpersonnes dépisté

. Les résultats patientes comcomplémental'inquiétude patelles que les

2. Les diagnosticdiagnosis andscientifique) clourds dont dela survie de la

tion de la qualitént pour objectif des avantages atteNi les données isselles recueillies e

lés randomisés nes stades métasmer ou de confe base. Par contrst inclue dans le melges dont noue valider cette as) font état de 58%totales dans les des bénéficiaires tement par radiothimiothérapie né

n des inconvénon de la qualité dvoque une diminutées. Ceci s'expliqu

faussement posmme de vrais posires n’ont pas pear rapport au cancponctions mammcs excédentaires d over-treatment,conduisent à des es amputations m

a personne.

é de vie des patide mettre en évidendus est de permsues de essais coen Belgique, ne pe

n’ont quantifié ni statiques de la firmer l’hypothèsere, la perte de qumodèle décrit ci-ds disposons acsertion. Les donn

% de chirurgie constades les moinsde la chirurgie c

hérapie, 38% d’eéo-adjuvante et

nients du dépisde vie des partiction de la qualité due par une série dsitifs du dépistagesitifs, aussi longteermis de les infirmcer du sein et aux

maires. et les traitements

, pour plus de dinquiétudes grave

mammaires qui n’o

ientes dence des tumeumettre des traitemontrôlés randomisermettent de conf

le taux de récidivmaladie. Il est

e d’une réductioualité de vie impuessous. ctuellement ne nées les plus récnservatrice versuss avancés (Stadeconservatrice reçontre elles reçoive

41% un traite

stage cipantes de vie d’une partiede facteurs: e sont perçus pamps que les exa

mer. Ils provoquex procédures inva

s qui les suivent (détails, voir le raes et à des traitemont pas d’influenc

11

rs de ments és, ni firmer

ves ni donc

on de utable

nous entes

s 38% s I et oivent ent un ement

e des

ar les mens

ent de asives

(over-apport ments ce sur

12

3. L’avance a

de vie en ble cancer ppatiente dede sa viindépendad’évoluer, sans que influencer s

4.3. ApprocLes revues de le poids des bspécifique danrechercher les dépistage et à l4.3.1. MesureDifférents instrCertains instrumpar exemple, latteintes d'un cTreatment of Cfonctionnementpas possible dimensionnellesindice global d(QALY). Les Qde vie. Les recommanle questionnairest un des meAvec cet instruen prenant enpersonne, les dépression. Popossibles. Cell

au diagnostic peubonne santé. Le dplus précocementevient de ce fait me. Toutefois, snte de son cancelle aura été “macette avance au

son espérance de

he par modélislittérature précitée

bénéfices et des s ce but. La coétudes relatives àa qualité de vie d

res de la qualité uments sont dispments sont spécle questionnaire

cancer du sein de Cancer (EORTC).t physiologique, lde prendre en s dans un modède qualité de vieALYs sont le nom

dations pharmace appelé EQ-5D eilleurs instrumenment, la qualité d compte cinq di

activités couraour chacune de ces-ci reflètent le

ut entrainer une pdépistage a pour t que ne le ferait umalade du canceri cette patientecer avant que cealade du cancer” u diagnostic et ae vie10.

sation es ne nous ayantrisques, nous avnstruction de ce à la qualité de viees patientes au cde la vie ponibles pour meifiquement adaptrelatif à la quall'European Organ

. Ces outils évalua peur de la réccompte ces do

èle. Elles doivene, à savoir, le Qmbre d’années de

co-économiques d(European Qual

nts disponibles pde la vie liée à l'émensions: la moantes, la douleces dimensions, niveau de sévé

S

perte de plusieursobjectif de diagn

un diagnostic clinr plus tôt dans le e décède d’uneelui-ci n’ait eu lequelques annéesau traitement n’a

t pas permis de qvons construit un

modèle a nécee des femmes peours de leur mala

esurer la qualité és à la maladie, ité de vie des pnization for Reseauent l'image du cidive… Toutefois

onnées de santént être convertiesQuality-Adjusted Le vie ajustées à la

du KCE, considèrity of Life-5 Dime

pour évaluer les tat de santé est m

obilité, l’autonomieur/la gêne, l’a

plusieurs réponsrité du problème

Screening Breast C

années nostiquer nique. La

décours e cause e temps s trop tôt aient pu

quantifier modèle

ssité de endant le adie.

de vie. comme

patientes arch and corps, le , il n'est é multi-s en un Life-Year a qualité

rent que ensions) QALYs.

mesurée ie de la nxiété/la ses sont e (aucun

ppsdpdbs1

2

PcssLcqrémplele4LcL

Cancer

problème, quelquproblèmes gravessoit en ce qui concdu cancer du seinpersonnes atteintd’identifier trois étbase de ces étudesont estimées com

. La perte de faussement ppour infirmermoyenne 45données AIM

2. Pour les patiele diagnostic (estimée à 16Pendant les a6% pour les pour les stade

Plusieurs limitatiochiffres avec précsaxons. Le questiosanitaires généralLes mesures conccompte l’impact questionnaire ayaésultats ne reflè

malades ne pouvapourraient expliques patientes ayanes patientes ayan4.3.2. DescriptioLe modèle compaconstituées de 10Le schéma ci-dess

ues problèmes, ) Ce questionnaircerne le dépistagn et en ce qui coes de ce cancertudes qui correspes, les variations mme suit:

qualité de vie copositif est estiméer ce faux positif.5 jours (minimum (Agence Intermu

entes cancéreuse(quel que soit le t% pour les stade

années suivantes,stades I,II,III. Ce

es IV. ons de cette appcaution. Il s’agit donnaire utilisé, à es et non les dimcernant les patienà court terme d

ant été utilisé lorètent pas la quaant plus se déplacer le faible changnt un cancer du snt développé des mon du modèle are deux cohorte0.000 femmes dosous représente c

des problèmesre est soumis à la e, une populationoncerne la maladr. La revue de londaient à nos cde la qualité de v

onsécutive à un e à 16% pendant . En Belgique, cm 36, maximum utualiste) s et pendant la praitement), la pert

es I, II, III et à 18 la perte de qualitette perte demeu

proche nous obligde résultats provsavoir, l’EQ-5D m

mensions spécifiquntes ne prennent qdu diagnostic etrs des consultatioalité de vie des cer. Les particulagement de qualitésein et la populatmétastases et cel

es théoriques. Ceont l’évolution est cette évolution:

KCE Report

s modérés, ou population conce

n de femmes indedie, une populatiola littérature a p

critères d’inclusionvie des septuagén

résultat de dépila période néces

cette période dur54 jours) selon

remière année qute de qualité de v

8% pour les stadeté de vie est estimure stationnaire (

gent à interprétevenant de pays amesure les dimenues au cancer du que sommairemet de la chirurgieons ambulatoires

patientes graverités de l’étude ut

é de vie constaté tion générale ou les qui n’en ont pa

es deux cohortessuivie jusqu’à la

t 176

des ernée, mnes on de ermis

n. Sur naires

stage ssaire re en n les

ui suit vie est es IV. mée à (18%)

r ces anglo-nsions

sein. ent en e. Ce s; ses ement tilisée entre entre as.

s sont mort.

KCE Report 176

Cohort

Cohorte

6

Femmes invitées 

Femmes non invité

te A 

e B

(1) diadép

(4)sit

(2) 

(3dgrpa

es 

(6dgrin

(7indn

S

cancer invasif gnostiqué lors du pistage 

) Cancer canalaire in u

cancer d'intervalle 

3) cancer invasif iagnostiqué dans le roupe des non‐articipantes 

6) cancer invasif iagnostiqué dans le roupe des non‐nvitées 

7) Cancer canalaire n situ diagnostiquédans le groupe des non‐invitées 

Screening Breast C

IIIIIIIV

IIIIIIIV

IIIIIIIV

IIIIIIIV

Cancer

(5) Décèscauses co

(8) Décèscauses co

  (toutes onfondues)

  (toutes onfondues)

13

14

La cohorte A illjusqu’à 74 ansParmi celles-ciet d’autres non cohorte sont rédépistage (1), sessions de dédes invitées/nopeuvent survendans le groupedes femmes cole cancer du seLa cohorte B (cmembres de cefemmes serontcanalaire in situcohorte décèdeLe cancer du sstade le moins d’autant plus lodiagnostic. 4.3.3. HypothL’hypothèse dedépistage, la prque parmi les bénéfice du déstades (stage-sL’autre hypothèfemmes dépenfemme au momdépistage. Les cohortes sparamètres deannée (incidenc

ustre l’hypothèses. Elle est consti, certaines partic(invitées/non-par

épertoriés. Il s’agsoit de cancers dépistage (2), soit on-participantes (nir dans le group

e des invitées/nononstituant cette coein (5). cohorte de contrôette cohorte ne st atteintes d’un u (7). La très granera d’une autre affsein évolue en quavancé. La survie

ourd et plus invas

hèses de base e base est la suiroportion de stade

cancers diagnosépistage provientshift) consécutive èse retenue est dent uniquement

ment du diagnost

sont suivies d’anne transition tels lce) et le taux de s

e d’une prolongatioituée des femmeipent au dépistagrticipantes). Les cgit soit de cancediagnostiqués dade cancer diagn

(3). Enfin, les cape des invitées/pn-participantes (4)ohorte décèdera

ôle) correspond àsont pas invitées cancer invasif (6

nde majorité des fection que le canuatre stades (I, II,e est d’autant mosif que le stade e

ivante: parmi les es peu avancés (Istiqués sur baset des différencesau dépistage. que la survie e

t du stade de la tic, que celui-ci s

née en année et le nombre de fe

survie en fonction

S

on du dépistage oes invitées au dége (invitées/particcancers survenanters diagnostiqués ns l’intervalle ent

nostiqués dans leancers canalairesparticipantes tout ). La très grande d’une autre affec

la situation actueau dépistage. C

6), d’autres d’unfemmes constitua

ncer du sein (8). III, IV). Le stadeins bonne et le trast avancé au mo

cancers détectéI et II) est plus im

e de la clinique. s dans la répartit

et la qualité de tumeur et de l’âg

soit consécutif ou

évoluent en fonemmes atteintes du stade du canc

Screening Breast C

organisé épistage. cipantes) t dans la

lors du tre deux

e groupe s in situ

comme majorité

ction que

elle. Les Certaines n cancer ant cette

e I est le aitement ment du

s par le portante Tout le

tion des

vie des ge de la non au

ction de chaque

cer.

4PndLdfocisBUmla“4Dsnàpdad

a

Cancer

4.3.4. AlimentatPour réaliser cet enotre modèle avedétails dans le chaL’espérance de vide la population fonction de l’âge ecancer (Communassues des prograBruxelles et en CoUne mesure de qmodèle. Le modèla situation la plus “Par essence, tous4.3.5. Analyse dDans notre modèsimplificatrices, ennécessité d’éviter à une incertitudeparamètres et dedifférents types d’iapprofondie utilisadécrits en détails d

citation attrib

tion du modèle exercice, nous avc des données bapitre 3.3. du rappe de la populatio

féminine belge duet des stades de lauté flamande). Lamme actuels (fommunauté Flamaualité de vie a étéle contient un casvraisemblable.

s les modèles sonde sensibilité èle, nous avonsn raison des dol’utilisation d’un m

e liée à la struce la source desincertitude, nous aant différents scédans la table 3.2 d

uée au statisticien G

vons autant que fbelges. Ces paramport. n étudiée provien

u même âge. L’inla maladie provienes données relati

femmes de 50-69ande). é appliquée à chas de base (base c

nt faux mais certa

émis un certain nnées dont nous

modèle trop compcture du modèle informations. Pavons réalisé uneénarios. Ces diffdu rapport scientif

George Box.

KCE Report

faire se peut, alimmètres sont décri

nt des tables de sncidence du cancnt du registre belgives au dépistage9 ans en Wallon

aque compartimecase) qui correspo

ins sont utiles”a

nombre d’hypoths disposions et plexe. Ce choix coe, au bon choix

Pour faire face àe analyse de sensférents scénarios fique.

t 176

menté its en

survie cer en ge du e sont nie, à

ent du ond à

hèses de la onduit x des à ces sibilité sont

KCE Report 176

5. RÉSULe scénario deans permettraitreprésente uned’années de vieL’analyse de sescénario optimiLe scenario pe20%, d’un taux vie de 0,19 perdrésultats). La actuellement daa été appliquéd’estimer un gapour 1000 femcertaines circonpeut aboutir à uLe scenario opd’un taux de fa0,13 perdurant la distribution dépistage orgapermet d’estimepour 1000 femnécessaire d’invpour gagner un

6

LTATS e base montre qut d’éviter 1,3 décèe réduction de 2e sauvées est estiensibilité du modèste . essimiste fait l’hyde faux positifs d

durant pendant 54distribution des

ans le cadre du dée au groupe dain de 8,7 annéemmes participantnstances, au demune perte en termetimiste fait l’hypotux positifs de 2%pendant 36 jourspar stades obs

anisé aux Pays-Ber un gain de 17,

mmes participant viter 62 femmes à QALY.

e la prolongationès pour 1000 fem21% des décès. imé à 13,1 et le gèle comprend un s

ypothèse d’un exde 10%, entrainan4 jours (temps nécancers dépisté

dépistage organisdépisté. Ce scénes de vie mais ut au dépistage. meurant tout à fae de qualité de viethèse d’un excéd

%, entrainant une ps. Ce scénario apservée actuellemBas (70-74 ans)0 années de vie

au dépistage. à participer au dé

S

du dépistage jusmes participantesGlobalement, le ain en QALY à 3,scénario pessimis

xcédent de diagnnt une perte de quécessaire pour infiés par stades oé en Flandre (50-nario pessimiste ne perte de 3,1 Ceci signifie qu

ait réalistes, le dée. ent de diagnosticperte de qualité dpplique au groupement dans le ca). Ce scénario oet un gain de 16,Ceci signifie qu’

épistage pendant c

Screening Breast C

squ’à 74 s, ce qui nombre

9. ste et un

ostic de ualité de irmer les

observée -69 ans)

permet QALYs

ue dans épistage

c de 3%, de vie de e dépisté adre du optimiste ,2 QALY ’il serait cinq ans

6Llafesdc

6LufeppfrLdEa2Ldtocredl’

Cancer

6. DISCUSLes résultats du ma situation de baemmes dépistéessensibilité. A l’invdes hypothèses ccertaines hypothès

6.1. Ajouter deL’augmentation deutilisés pour justifiemme âgée de population des spopulation des sréquence et les caLe nombre de dédeux fois et demi En fait, la populatians, 8% entre 60 2009). Les causes de dédécès dus au canous les décès encomme la mortalesponsables chac

décès, la part de dâge (KCE report

SSION modèle décrit ci-dese, le gain en ans. Ce résultat resverse, les QALYschoisies, allant dses plausibles, un

es années à la e l’espérance de er de poursuivre plus de 69 an

septuagénaires aexagénaires. Il nauses de décès.

écès observé danplus élevé que ceon féminine belgeà 69 ans et 20%

écès varient égalncer du sein passntre 70 et 75 ans.ité cardiovasculacune d’un peu pludécès consécutifs11).

essus indiquent qnnées de vie est ste fiable tout aus varient substand’un gain relativene perte en qualité

vie ? vie de la femme le dépistage du cs. Cet argumen

a les mêmes can’en est rien en

ns la tranche d’âgelui de la tranchee perd 4% de ses% entre 70 à 79

lement. En Belgiqse de 13% entre A cet âge, la mo

aire sont pratiqueus d’un tiers des s au cancer du se

ue en ce qui concde 13 ans pour

u long de l’analysntiellement en fonement faible à, é de vie.

est un des argumcancer du sein cht présuppose qu

aractéristiques qun ce qui concern

ge des 70-79 ane d’âge des 60-69s effectifs entre 50ans (Belgian life

que, la proportion60 et 64 ans à 6ortalité par canceement équivalentdécès. Parmi tou

ein diminue donc

15

cerne 1000

se de nction selon

ments hez la ue la ue la ne la

ns est 9 ans. 0 à 59

table

n des 6% de er tout es et us les

avec

16

6.2. Ajouter 6.2.1. TraitemOutre le gain enest de permedonnées issuesrecueillies en B6.2.2. Faux pDans notre modsource importafaussement pod’attente relativcomplémentairetermes de QAeuropéennes (3Flandre), le gai6.2.3. Excès Le risque de dipour les septua%, on peut s’at108 femmes sutrès vraisemblasurdiagnostic dD’autre part, tscreening deviecas de diagnosannées de vie q

de la (qualité dments moins agrn années de vie, ttre des traitems de essais contrô

Belgique, ne permepositifs dèle, les diagnostnte de perte de q

ositifs (pouvant avement élevé (45es peut amener à

ALY. Si on parvi3,5%) comme c’en en QALY est dede diagnostics eagnostic excéden

agénaires. Si nousttendre à ce que dupplémentaires aablement un traie 10 %, ce nombrtoutes les femmeennent malades dstic clinique. Cecqui leur restent.

de) vie aux annressifs? le principal avantaents moins agreôlés randomisés, ettent de confirme

tics ”faussement qualité de vie. Ualler jusqu’à 10%5 jours en moyeà un résultat totaent à garder ceest le cas dans e 3 pour 1000 femet de traitementsntaire est le risques appliquons un tadans chaque cohuront un diagnostement. Si nous re monte à 367. es dont le cancdu cancer deux oci a un impact n

S

nées ?

age attendu du déessifs. Toutefois,ni les données fa

er cette attente.

positifs” représenn taux élevé de r%) conjugué à uenne) pour les el du dépistage né

e taux dans les une région du p

mmes. s e majeur de ce déaux de surdiagnosorte de 100.000 f

stic de cancer et appliquons un

cer est diagnostiqou trois ans plus tnégatif sur la qua

Screening Breast C

épistage , ni les actuelles

tent une résultats un délai examens égatif en

normes pays (en

épistage stic de 3 femmes, subiront taux de

qué par tôt qu’en alité des

77LCdmdinréppdsLsjuLsdbqsLprécdv

Cancer

7. CONCLU7.1. Faut-il proLa conclusion de Cette affirmation d’autre part sur lemodèle démontredépistées. Toutefondiquent que le ésulter en une pe

pas décisifs en taparticulier d’un dédéfinition à un ispécificité impliquLes trois principessont: les principesustice ou d’équitéLes principes de bsuit: “Ne pas fairedoubler d’un devobienveillance”. Le qui fait intervenir lsens d’une préféreLe dépistage estpopulation en évitésultats obtenus

certaines situationde vie dans la tranviolation du princip

USIONS olonger le dépiscette étude est qest basée, d’une

e contexte spécifiqent un gain de 1ois, certaines hyp

résultat net duerte globale en quant que tels et doépistage organiséndividu qui n’exe d’être d’autant

s éthiques de bass de bienfaisance et le principe d’abienfaisance ou de de mal (primumoir de bienfaisancprincipe de justic

la dimension colleence pour les plust organisé dans tant notamment dpar le modèle n

ns, le dépistage pnche d’âge étudiépe de base ”primu

stage jusqu’à lue la réponse à ce part, sur les réque de cette que13 années de vipothèses qui sont prolongement d

ualité de vie. Ces oivent être interpré. Le dépistage oxprime ni plainte

plus vigilant auxse applicables note ou de non malfautonomie12.

de non malfaisancm non nocere) esce qui va de pairce ou d’équité estective des problèms faibles, les plus le but d’amélior

des décès prémane permettent papuisse affecter née. Dans ces condum non nocere”(ne

KCE Report

’âge de 74 anscette question estésultats du modèstion. Les résultae pour 1000 femt loin d’être irréaldu dépistage porésultats ne sont

rétés dans le conorganisé s’adresse ni demande. x principes éthiqutamment au dépiaisance, le princip

ce sont définis cost le premier. Il dor avec une attitudt: “cette préoccupmes de santé, dadémunis”12.

rer le bien-être daturés. Cependanas d’exclure que égativement la qditions, il y a risque pas faire de ma

t 176

s ? t non. èle et ats du mmes listes, ourrait

donc ntexte e par Cette ues11. stage pe de

omme oit se de de pation ans le

de la nt, les

dans ualité ue de l).

KCE Report 176

D’autre part, ledont l’espérancexiste certes dprononcée. Le être une raisonposée.

7.2. Que répLe contexte deen deux pointssur un plan indbien à cette sitpersonne est lpersonne en dfaire des choix sa conduite (achoix, il imporavantages et personnelle. Leéclairé sont déconsentement base de la lectudevrait idéalemIl convient égademande le déAinsi, une attitu• Information• Prise de d

patiente14.• Orientation

modalités m

6

e dépistage est nce de vie est la dans les autres respect du princ

n supplémentaire

pondre à la per cette question d

s: l’individu est deividuel. Le principuation. Ce principle principe de bécoule ; Il s’agit pour lui-même (a

utogestion)”12. Porte qu’elle soit c

des inconvéniee droit d’être inforécrits dans la loi éclairé de la patiure d’un documenent inclure un éch

alement que le mépistage, une straude articulée en tron spécifique à la trdécision en fonc

n de la personne minimisent les inc

ettement moins eplus basse. Cetranches d’âge

cipe de justice oude répondre par

rsonne qui demdiverge de celui demandeur et le ppe d’autonomie s’pe est défini comase, le respect de reconnaître laautodéterminationour que la persoclairement et corents du dépistarmé (Article 7) et belge relative auente ne peut être

nt d’information. Ilhange d’idées avemédecin dévelopatégie qui en miniois étapes peut êtranche d’âge ction de l’appréc

qui le souhaite veconvénients.

S

efficace pour les tte différence d’emais elle y es

u d’équité se révèla négative à la q

mande un dépise la question pré

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nis dans le cadrurveillance de lalecture des mamue, les unités de ns le cadre du prmes qui demande

clé t organisé dans ant notamment dtage jusqu’à l’âgede vie. Toutefo

est nettement plte intervention pode vie. Dans ces

de ce dépistage pulation.

re du programmea qualité techniqmographies et l’omammographie a

rogramme européent explicitement

le but d’améliores décès prématu

e de 74 ans devraois, l’influence delus aléatoire. Seourrait même abconditions, il se ppenche du côté d

e européen prévque des équipemoptimisation du tauagréées répondanéen, il est donc loun dépistage ver

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ait permettre de gae cette mesure selon des hypothboutir à une pertpourrait que la bad’une perte globa

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1. Perry NL. EuroscreeniOncol.

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4. SilvermFischhomammo2001;2

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RENCES N, Broeders M, deopean guidelinesing and diagnosis2008;19(4):614-2rtz LM, Woloshinography for womtion of breast canrtz LM, Woloshin cer screening in

man E, Woloshin off B. Women's vography: a qualit1(3):231-40. rtz LM, Woloshin

n's attitudes to faon of ductal carci20(7250):1635-40n Cancer Registr005. Brussels; 20D, Mambourg F,

Clinical Practice (Gedge Centre (KCEble from: ce.fgov.be/index_

e Wolf C, Tornbergs for quality assus. Fourth edition--22. n S. News mediaen in their 40s acer. JAMA. 2002;S, Fowler FJ, Jr.the United States

S, Schwartz LMviews on breast ctative interview st

S, Sox HC, Fiscalse positive manoma in situ: cros0. ry, editor. Cance

008. Bonneux L. [Brea

GCP). Brussels: BE); 2005 02/05/200

_en.aspx?SGREF

S

g S, Holland R, vourance in breast-summary docume

a coverage of scand tamoxifen for 287(23):3136-42.., Welch HG. Ents. JAMA. 2004;29

M, Byram SJ, Wecancer risk and sctudy. Med Decis

chhoff B, Welch ammography resuss sectional surve

er incidence in B

ast cancer screenBelgian Health Ca05. KCE Reports

=5221&CREF=93

Screening Breast C

on Karsa t cancer ent. Ann

creening primary

. husiasm

91(1):71-

elch HG, creening Making.

HG. US ults and ey. BMJ.

Belgium,

ing]. re 11

348

8

9

1

1

1

1

1

Cancer

8. MandelblaDraisma different benefits a19;152(2):

9. Woloshin HG. Womdebate. Ar

0. Mandelbladecisions among theClin Onco

1. Doumont organisé.

2. Gallois. DUNAFORM

3. USPSTF. Task ForMedicine 2

4. Woloshin mammogr2010;303(

att JS, Cronin KAG, et al. Effectscreening schednd harms.[Erratum:136]. Ann Intern S, Schwartz LM,

men's understandrch Intern Med. 20att JS, Silliman about the benefitse oldest old withol. 2009;27(4):487-D, Verstraeten

Santé en CommuDépister les caMEC, editor. MédScreening for Br

rce Recommend2011(151):716-26

S, Schwartz raphy screening: (2):164-5.

A, Bailey S, Berrs of mammogradules: model esm appears in AnnMed. 2009;151(10Byram SJ, Sox H

ding of the mam000;160(10):1434R. Hanging in s and harms of br

out a safety net o-90. K. Enjeux éth

unauté Française.ancers, mais à ecine. Paris; 2005reast Cancer: U.Sdation Statement6.

LM. The beneunderstanding t

KCE Report

ry DA, de Koningaphy screening ustimates of pot

n Intern Med. 20100):738-47.

HC, Fischhoff B, Wmmography scre4-40.

the balance: mreast cancer scre

of scientific eviden

hiques du dépi 2012(7):3-7. quelle condition

5. p. 72-7. S. Preventive Sert Annals of Int

efits and harmthe trade-offs. JA

t 176

g HJ, under tential 0 Jan

Welch ening

aking ening

nce. J

stage

n In:

rvices ternal

ms of AMA.

KCE Report 176

SCIE

6

NTIFIC RREPORT

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1. INTROD1.1. Context oThis report is a pbreast cancer scrmade a list of cRepresentatives ohe choice and theelated to each

questions(see KCover three KCE rebreast cancer screof 40-49 years (KCof women at risk foscreening (KCE re

1.2. Scope of This report focusewith mammograpwomen between 7

1.3. Breast caThe Belgian fedagreement in 200aged 50-69 yearsappropriate financ2001, Flanders, theach introduced acontext of alreademains quite freqn the age-group 5older women (>7dominant in the agdrops, mainly becaby means of diagnhat substitution o

DUCTION of this report artial update of teening publishedclinical questionsof stakeholders’ ore wording of the q

question and CE report 172)2. eports. A first KCEeening with mamCE report 129)3. or breast cancer aeport 172)2.

this report es on the extensiohy to older wom

70-74 years of age

ancer screeningderal and regio01 for an organis, to be organiz

cial resources suphe Walloon regionan organized scredy existing practquent in the Wallo50-69, but also a

70 years). In Flage-group 50-69. Iause organized scnostic mammograf screening mamm

he clinical practicd in 20051. Theres related to brearganizations wereuestions, to highlito score the

Selected questioE report published

mmography for woThe second is foand technical met

on of organized brmen. Eligible pope with average ris

g in Belgium nal governmentszed screening p

zed by the regiopplied by the feden and the Brusseeening programmtices. Indeed, opoon and Brussels among younger (4nders, screeningn the age-group 7creening stops at

aphy decreases amography by opp

ce guideline (CPGfore, the KCE exast cancer screee then invited to reight the main probrelevance of cl

ons were then did in 2010 is focuseomen in the age gcused on identificthods for breast ca

reast cancer screpulation is definek of breast cance

s signed a prorogramme for wonal governments

eral government. Sels capital region me within their sppportunistic screregion among wo

40-49 years of ag mammographies70-79 overall coveage 69. The covelso with 3%, indic

portunistic screeni

19

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ening ed as r.

otocol omen

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pecific ening omen ge) or s are erage erage cating ing at

20

the age of 70 (including both screening) remWalloon region

1.4. ClinicaThis specific re1. What are c

screening i1.1. What

organi1.2. How lo

breast1.3. What

organi1.4. What

organi2. What are

organized sterms

2.2. Harms2.3. Harms2.4. Harms

3. What attitureferral?

is not frequent diagnostic or foll

mains at 18% in F(KCE report 172)

l questions port addresses thclinical benefits ofin women betweeis the effect of anzed screening onong is the delay bt cancer related mis the effect of anzed screening onis the effect of anzed screening onthe specific ha

screening in womof false positive o

s in terms of addits in terms of over-s in terms of overtude should be re

in Flanders. At low up mammogr

Flanders, 33% in )2.

he following questif an extension of

en 70 and 74 yearsn extension (70-74 the breast cancebetween the scree

mortality reduction?n extension (70-74 the overal mortal

n extension (70-74 morbidity? rms of an exte

men between 70 or false negative reional diagnostic te-diagnosis? treatment? ecommended for

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this age, total craphies and oppoBrussels and 30%

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er related mortalityening and the as? 4 years) of breaslity? 4 years) of breas

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1.5. Scientific For each clinical performed and disheir scientific coepidemiology, or models. To quanBelgian situation IMA/AIM), cancerables and construcycles. The methodology

approach question, a sys

scussed with the ompetency in se

health economicntify what the im

we applied dar registry and datucted a simple tim

used and the resu

stematic search support of extern

everal fields: gycs. For question

mplications of ourata from the Inta from the literat

me dependent Ma

ults are described

KCE Report

of the literaturenal experts choseynaecology, radion 3, we searcher findings are ontermutualistic Agure on the Belgiarkov chain with a

d in each chapter.

t 176

was en for ology, ed for n the gency an life nnual

KCE Report 176

2. LITER2.1. Review2.1.1. Metho2.1.1.1. SouA broad searcCDSR and DARfor systematic r2.1.1.2. SeaFor searching oin combination screening (or eEMBASE, the 'breast cancer'combined with(SR) or meta-an2.1.1.3. In- Databases werGerman. This r2004), thus wrestriction (Engselection basedwithout breastintervention (mdiagnosis testsanalysis or RC<75 years), anindependently b

6

RATURE REw of clinical studodology urces ch of the electroRE was conductedreviews (SR) and arch terms on Medline databwith usual langua

early detection) (following Emtre

and 'mammograpa standard searc

nalysis (M-A). and exclusion crre searched for Sreport is a update

we used a date lish, Dutch, Frencd on title, abstrat cancer and w

mammography), o, over diagnosis

CT), key questiond original publicaby 2 reviewers (FM

EVIEWS dies

nic databases Od in April 2011. Semeta-analysis (M

ase, the followingage: Breast neop(MESH) and mame terms were u

phy'. These MESHch strategy to ide

riteria SR and M-A in Ee of previous KCE

restriction (2004ch and German).act or full text wwithout particulaoutcome (mortaland over treatme (screening), age

ation. Relevant puM, JR).

S

OVID Medline, EMearch was conduc

M-A).

g MeSH terms welasms (MESH) an

mmography (MESused: 'cancer scrH and Emtree termentify systematic

English, French, DE report1 (search 4-2011) and a laInclusion criteria

were: population ar breast canceity, morbidity, a

ent), design (SR oe of population (>ublications were

Screening Breast C

MBASE, cted first

ere used nd mass SH). For reening', ms were reviews

Dutch or made in anguage used for (women

er risk), dditional or meta->70 and selected

2WquR2eresTeaTs2Tb(wwTu(wT2InwefuwTmd

Cancer

2.1.1.4. AdditioWe identified twoquestion 2. Therupdated by searchReviews from the2008). Additional hensure that no poeference lists of

screening3. The identified stueligible studies, available, the studThe description asearch are in Appe2.1.1.5. QualityThe methodologicbias were rated www.cochrane.nl

was conducted byThe methodologicusing the adeqwww.cochrane.nl

The results of the 2.1.1.6. Identifn the systematic were identified inexcluded on the bull and reviewed were included4-8. The reviews writtemortality as outcodiagnosis and the

onal evidence SR4, 5 as the mrefore the evidehing Medline and search date of thand searching otentially relevant f SR and of ou

dies were selectethe full-text was

dy was not taken innd results of the endix 1.1. ty appraisal cal quality of syst

using the check). The assessmen

y a team of two revcal quality of selecquate checklists ). quality appraisal afied systematic r

search for literan database searbasis of title and in more detail. O

en by Götzsche ome, those from review of Virnig8

more extensive soence-identified th the Cochrane Dthe two SR’s on

of reference lists wstudies were misur previous repo

ed based on titles retrieved. In cnto account. literature searche

tematic reviews aklists of the Dunt of the risk of bviewers (FM, JR).cted additional ev

of the Dutc

are in Appendix 1reviews ture reviews, 53

rches. The majoabstract; 10 citat

On the basis of t

and Nelson4, 5 aBiesheuvel and Jon ductal carcino

ource for the reserough those SRatabase of Syste(search date Nov

was also undertaksed. We also scaort on breast ca

e and abstract. Fcase no full-text

es and flow of st

and associated ritch Cochrane C

bias in the include. vidence was also h Cochrane C

.5.

citations on the ority of citations tions were retrievthe full text, 5 rev

are mainly focuseJorgensen6, 7 on ma in situ (DCIS)

21

earch R-was matic v-Dec ken to anned ancer

For all was

tudies

isk of Centre ed SR

rated Centre

topic were

ved in views

ed on over-.

22

As a first step,determine theirjudged to be ofupdate of onePreventive Tasquality and useThe review writappraisal of seJorgensen7 waswas also judged2.1.1.7. IdenThe evidence wsearching Medfrom the searchsearch for relevApril 2011) idenon the basis offull and reviewstudies were exthe flow of randBy hand searcSwedish RCT’sonly RCT tharandomization. their suitability fquality by Nelsanalysis10. 2.1.1.8. IdenFor diagnostic July 2011 identon the basis oretrieved in fullthose two stucomments on th

, a quality apprar suitability for incf high quality withe other review sk Force9. Humphd here as completten by Biesheuvelected trials not ss judged to be ofd to be of high quntified RCT

was updated usingdline and the Coch date of this SR vant RCTs carrientified 432 citationf title and abstract

wed in more detaxcluded because

domized controlledching of referencs were identified. at includes wom

Quality appraisalfor inclusion. Theon and of low qu

ntified additionaerrors and over-tifying 10 citationof title and abstr and reviewed indies were excluhe two main SR4,

isal of all the revclusion. Götzsche a low risk of biasperformed by H

hrey review was aementary informatel6 was judged to bsufficiently describf high quality. Theality.

g the key words rchrane Databaseon (search date d out in Medline,ns. The majority ot; the other paper

ail. On the basis of the study desd trials from selecce lists of GötzsAmong those, the

men aged 70-74l of this RCT was Two County trial

uality by Götzsche

l evidence -diagnosis, this us. The majority oract; 2 papers on more detail. On ded. Most pape5.

S

views was carriee and Nelson SR4

s. Nelson review5

Humphrey for thalso judged to beion source. be of good qualitybed) and those we review written b

eported in Nelsone of Systematic RNov 2008). The l EMBASE and C

of citations were ers (n=8) were retrof the full text,

sign (not an RCTction to in-or exclusche and Nelsone Two County tria

years at the s carried out to des was judged to be and included fo

pdate was carrieof citations were en diagnostic errothe basis of the

ers are discussio

Screening Breast C

d out to 4, 5 were 5 was an he U.S. e of high

y (quality written by by Virnig

n SR5 by Reviews iterature

CCRT (in excluded rieved in all eight

T) shows sion. 4, 5, the

als is the time of

etermine be of fair or further

ed out in excluded ors were full text,

ons and

FAFcoobsSin2Ins‘smrecp2Ded22Incth((trIn8in

Cancer

For DCIS, this updAll citations were eFor overtreatmentcitations on Medlinof citations were eovertreatment werbasis of the full teselected one pubScreening Programn Appendix 1.4. 2.1.1.9. Ongoin addition to the searched for clinicscreening’ and ‘mmajority of searchelevant trials (NC

considered as ouprotocol. 2.1.1.10. Data eData from systemextraction table (Ddata extraction tab2.1.2. Descript2.1.2.1. Sourcn the years 196conducted randomhe HIP trial (N =phase I and II, N Kopparberg and rial (N= 60 117) inn Canada, the Na835) were initiatedn 1979 in 1980 (N

date was carried excluded on the bt, this update wasne and 7 citationsexcluded on the bre retrieved in fu

ext, we retrieved ablication presentimme11. The desc

ing clinical trials database search

cal trials. The seamammography’ wh results (n=135CT00963911, NCt of scope after

extraction matic reviews andDET) summarizinble are in Appendition of screeningces 60-1980, USA, Smized controlled tr= 60 995) started= 60 076) startedOstergötland, N=

n 1980 and finallyational Breast Scd in 1980. In UniteN=44 268) and th

out in July 2011 basis of title and as carried out in Jus on the Cochranebasis of title and ll and reviewed iagain the SR writing data issued ription and results

hes, the ClinicalTarch terms ‘breastwere used to se5) were ongoing CT00247442) wer

receiving more i

from trials wereng key design feaix 1.6.

g benefit

Sweden, Canada rials of mammograd in 1963. In Sw in 1976 and 1978= 133 065) in 19y the Göteborg triacreening Trials (Ned Kingdom, the Ehe UK Age Trial i

KCE Report

identifying 7 citabstract. uly 2011 identifyine Library. The maabstract; 2 papen more detail. Otten by Götzschefrom the UK B

s of those update

Trials.gov websitet neoplasm’ as warch for studies.trials. Two potenre identified but information on th

e extracted into aatures and result

and United Kingaphy screening. In

weden, the Malmö8, the Two county977-78, the Stockal (N= 51 611) in NBSS-1 and 2, N Edinburgh, trial stin 1991 (trial limit

t 176

tions.

ng 19 ajority ers on n the 4 and

Breast es are

e was well as

. The ntially were

he full

data ts. All

gdom n US, ö trial y Trial kholm 1981. = 89

tarted ted to

KCE Report 176

women aged summarizing thThis part is baPreventive Servon the CochranSwedish Two-CSR10,13,14. Both reviews inMalmö I and Stockholm trialstudy was ratedNelson updatedabout youngerHumphrey pubfrom 50 to 74 women 39 to 74younger than 50Two-County trWe analysedinformation on County trial is therefore threepublication of thby Nelson and Two-County triHealth and WKopparberg andyears were clstratified by socluster. Finallythose, they werand 7 462 in tscreening rounclosed in 1984

6

40-49 years)12. eirs results are noased on the SRvices Task Forcene SR 4. We anaCounty trial (Ost

ncluded the sameII, the Two coun, the Göteborg trd as poor quality bd the meta-analys

women (40-49 yblication for morta

years. Götzsche4 years of age. T0 years and for w

rial the Swedish Tour specific popthe largest of th

e publications thahe initiator10, the pthe last publicatial was commiss

Welfare and includ Östergötland. Inuster-randomized

ocioeconomic stat, 78 085 womenre 10 568 womenthe control groupnds with a screenafter approximate

Numerous publow available.

R (2002) commisse (USPTSF) and alysed more in detergötland) which

e trials in their menty trial, the NBSrial and the UK Aby both authors ansis from Humphreyyears of age). Thality analysis pere4 performed firstThen he did a sepwomen older than 5

Two-County trial ulation (70-74 ye

he first eight randat describe this spublication of Nyson of Tabar publioned by the Swuded women in n 1977-78, 134 8d by geographictus, urban or ruran were invited ton aged 70-74 yea. At this age, woning interval of 3ely 7 years of scre

S

lications and so

sioned to assist its update of 200

etail one RCT nah was included

eta-analysis: the HSS trials (1 and Age Trial. The Ednd excluded therey9 to include new herefore, we referformed on womet a meta-analysisparate analysis for50 years.

in order to finears). The Swedisdomized trials. Wstudy. We used ström13 who was sished in July 201

wedish National Btwo Swedish c

67 women aged 4 area. They weal residency, ando the screening. rs in the screenin

omen were invited33 months. The teening10.

Screening Breast C

ome SR

the US 095,9 and med the by both

HIP trial, 2), the

dinburgh efore4, 9.

findings er to the en aged s among r women

nd more sh Two-

We used the first selected 114. The

Board of counties: 40 to 74 ere also d size of

Among ng group d to two trial was

InthKthmfrUoeFoTAadaNloSnseaOwavCtoca

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n 2002, Nyström he Malmö, OsteKopparberg trial whe age-dependenmortality relative rrom the OstergötUnfortunately, withof women 70 to 74each group)13. Finally, we found on mammographicTrials quality andAll studies includeas fair5, 9. Götzsdivided his resultsand results based Nevertheless, the ow risk of bias (seSome publicationsnumbers of womesome studies anaexact age at randas suboptimally raOstergötland, a puwitnesses were pralmost twice as hversus 0.0012, p County trial and cao that the validitycommittee (nameda doubtful cause o

performed one rergötland, Stockhwere not availablency of the effectrisks for consecuttland trial. The mhout the Kopparbe4 years of aged e

one publication sc screening effectd bias ed by Humphrey ische assessed ths on results based

on suboptimally rthird meta-analy

ee Appendix 1.5.1s based on The n enrolled. To exalysed results bydomization13. Nevandomized and lublic notary allocaresent. Breast cahigh in Kopparbe

= 0.02). The auause-of-death ass

y of local end poind consensus comof death14.

review of the Swholm, Göteborg e at this time. Thist of screening. Tive 5-years age g

median follow-up erg part of the Swenrolled was low (

summarizing longt on mortality14.

in 2002 and later he randomizationd on adequately rarandomized controyses were judged

). Swedish Two-Coplain this variation

y year-of-birth whvertheless, Götzscikely to be biase

ated the clusters bancer mortality in erg compared to utopsy rate was sessments were nnt committee datamittee) reviewed

wedish RCT’s incltrials. Results os publication asseThe author calcugroup based on retime was 17.9 y

wedish trial, the nu(approximately 50

g term data (29 y

by Nelson were n quality. This aandomized controol trial4. of high quality w

ounty reported van, Nyström replied

hile some others che assessed thised. He argued thby tossing a coin the control groupOstergötland (036% for all the

not blinded4. Accoa was criticized, athe records conta

23

uding of the essed ulated esults years. umber 000 in

years)

rated author ol trial

with a

arying d that used

s trial at for while

p was .0021 Two-

ording a third aining

24

2.1.2.2. BreFor women ageup, the Humphra significant re(RR) 0.84, 95%Risk (RR) 0.81,For women agcontrol trial sho15.8 years (me0.70 to 0.89). Tin terms of brrange13. For women agerandomization mortality at 13 ytrials with subbreast cancer mseven trials comThe review oconservative deat randomizatiomortality at 17.this age group group) and thistogether with N2.1.2.3. DelTabar publisheSwedish Two-Cmortality reductissued from locpresented. Thepresent here cpublication sho(CI) 0.62 to 1.0respectively 10

east cancer related 39 to 74 yearsrey meta-analysiseduction in breas% confidence inte, 95% (CI) (0.74, 0ged 39 to 74 yeowed a significan

edian follow up) oThis study showedreast cancer mor

ed at least 50 y adid not show a

years (Relative Roptimal randomizmortality (RR of 0mbined was 0.77 (of Swedish randetermination of caon, did not show4 years ((RR) 1.1was relatively sm

study is underpoelson that data arlay between screed in July 2011 County Trial14. Ttion in function of cal end point com validity of local econsensus data.

owed specific mor05), 27% ((RR) 00, 15 and 20 to 2

ted mortality reds and at approxims (M-A)9 and the Cst cancer mortaliterval (CI) 0.77 to0.87) respectivelyars, the Review nt reduction in b

of 21% (Relative Rd that the effect ofrtality reduction

at randomization, ta significant redisk (RR) 0.94, 95%zation showed a

0.77 (95% CI 0.67(95% CI 0.69 to 0

domized control ause of death for ww a significant re12, 95% (CI) 0.73mall (approximate

owered13. Conseqre insufficient for teening and specthe last follow-up

This publication mlength of follow u

mmittees and conend point committe

For women agertality reductions 0.73, 95% (CI) 0.29 years of follow

S

duction mately 13 years oCochrane review4

ty of 16% (Relat0.91) and 19% (

y. of Swedish rand

reast cancer moRisk (RR) 0.79, 9f breast cancer scvaries according

three trials with auction in breast % (CI) 0.77 to 1.1

a significant redu7 to 0.83)). The R0.86)4.

trial, applying women aged at leduction in breast3 to 1.72)). Unfortely 5000 womenuently, we must cthis age group5. cific mortality redp result (29-yearmodulated breastup. In this report bnsensus-based daee data was criticed 39 to 74 yeaof 20% ((RR) 0.8.59 to 0.92), and w up. In the sam

Screening Breast C

of follow-showed

ive Risk (Relative

domized rtality at

95% (CI) creening to age

adequate cancer

5). Four uction in RR for all

a more east 70 y t cancer tunately, in each

conclude

duction r) of the t cancer

both data ata were ized, we ars, this 80, 95% 27% at

me time,

dledinpfuaAs(wthsfrAinw2Ta(ysre1Umfrre2Wss

Cancer

deaths from breasength of follow-udeaths prevented ncluded in this sprevents deaths muture. So most oabsence of screenAuthors did not separately. Result77 080 in the scre

were 10 568 womehe control groupscreening rounds rom these cases wAs cited on previon the Swedish Twwomen in each gro2.1.2.4. All-cauThe Cochrane SRaged at least 50 y n=73654) did not

years (Relative Risuboptimal randoeduction in all-ca.02))4.

Unfortunately studmortality reductionraction of all-causeduction would re

2.1.2.5. MorbidWe found no datasources. In other screening reduces

st cancer preventup. They were reat 10, 15, 20, 25

study. Author empmore in the mediuf the breast canc

ning) more than 10calculate mortalits presented are eening group anden aged 70-74 yep. In Kopparberin women aged

were still includedous point, the grouwo-County Trial woup) and this studuse mortality R has reported d

at randomizationt show a significask (RR) 1.00, 95%

omization (n=982use breast cance

dies did not haven. According to thse mortality in caequire inclusion ofdity reduction a related to the cwords, we do no

s the morbidity of t

ted in the study gespectively 50, 9and 29 years of fphasized that breum to long term cer deaths would 0 years after randity relative risks based on 133 06 55 985 in the con

ears in the screenrg, cancers diag70-74 years and

d in the results14.up of women agedwas relatively smady is underpowere

ata on all-cause, two trials with adnt reduction in al% (CI) 0.95 to 1.0

261) also did noer mortality (RR of

statistical power hat disease specincer screening trf millions of subjec

cancer related moot accept or rejethe breast cancer

KCE Report

group increased 99, 114, 122 andfollow-up for all woeast cancer screthan in the immehave occurred (i

domization. for each age g

65 women aged 4ntrol group), whileing group and 7 4

gnosed after the breast cancer d

d 70-74 years incall (approximately ed13.

mortality. For wodequate randomizl-cause mortality 04). The two trialsot show a signif 0.99 (95% CI 0.

to detect an all-cific mortality is a rials, detect a moct.

orbidity in our select the hypothesisr disease.

t 176

along d 126 omen ening

ediate in the

group 40-74 e they 462 in e two eaths

luded 5000

omen zation at 13

s with ficant .97 to

cause small

ortality

ected s that

KCE Report 176

2.1.3. Descr2.1.3.1. SouThis part is basin part 2.3.5, wesearch date. Se2.1.3.2. StuSR written by reviews writtendiagnosis and different methoissued from thpublicly organizwas focused on2.1.3.3. PerThe sensitivity 81% in the Twdifficult to intebecause they replacement th(quality of mamfactors (the exresults of an esensibility mayspecificity of a aged 40-74 yecancer underwvalue of one-timfurther evaluatibiopsy. Positiveto 20% among Nelson reporte(USA) BCSC foa single screencommon amon

6

ription of screenurces sed on the 5 SR see updated those iee more details in

udy description Götzsche and N

n by Biesheuvel asubsequently on

ods to address e first RCTs whized screening prn ductal carcinomarformance of maof first mammog

wo County trial. Trpret. This data are not adjuste

herapy, mammogmmography, numxperience of radioexamination abnoy vary between

single mammogrears. This indicatewent further diagnme mammographion and from 50e predictive valuewomen 70 years

ed data from theor regularly screenning round. False

ng women aged

ing harms

elected in our main July 2011 starti appendix 1.4.

Nelson are descrand Jorgensen6,

n overtreatment. this issue. Biesile Jorgensen anrogrammes. The a in situ (DCIS)8.

ammography graphy for womenThis includes ovecannot be appli

ed for patient fagraphic breast deber of mammogrologists and thei

ormal)9. Provider countries4. In thraphic examinatioes that 4% of wnostic evaluationhy was 12% for a% to 75% for ab increases with aof age or older9. Breast Cancer ned women that ae-positive mamm70-79 years (68

S

in search4-8. As exing from the last l

ribed in point 3.17 were focused oEach author us

heuvel analysed nalysed data issu

review written b

n aged 70-74 yeer-diagnosis and ed to individual actors (use of hensity), technicalraphic views) or r propensity to lafactors may expe Two County t

on was 95.6% forwomen who did n

. The positive pabnormal results rbnormal results r

age and ranged fro

Surveillance Conare based on resuography results .8 per 1000 wom

Screening Breast C

xplained iterature

1.1. The on over-sed very

reports ued from by Virnig

ears was may be patients

hormone factors provider abel the lain that trial, the r women not have redictive requiring requiring om 18%

nsortium ults from are less men per

sliw2Ryhsoswoao2OddaNwebsGRsthbUBYENo

Cancer

screening round). ttle more commo

women per screen2.1.3.4. AdditioRates of additionayears (64.03 per higher among woscreening round) of screen detectedscreen-detected inwomen per screenof invasive breast aged 70 to 79 yeaother imaging test2.1.3.5. Over-dOver-diagnosis ofdetection with screduring the womanabsence of screenNelson reported rawith most from 1exclusion of DCISby age. She conclstatistically5. Götzsche reportedRCT’s that did nosomewhat larger ihe control group.breast cancer in oUSA after beginninBiesheuvel analyYork/HIP, Malm IIEdinburgh) and froNetherlands and over-detection of

Conversely, falseon among womening round)5. onal diagnostic t

al imaging are rela1000 women pe

omen aged 70 tothan among youn

d cancer is highesnvasive cancer aning round. The B

cancer detected ars, 154 women h, and 2 have biopdiagnosis f breast cancer eening of cancer n’s lifetime (and thning)6. ates of over-diagn1% to 10%. She

S cases, by whethluded that the stu

d that the level oot introduce earln the sub optimal He found also a

observational studng of the screeninysed publicationsI, Two County, Com four populatioItaly). He selectinvasive breast

e-negative mammn aged 70 to 79

tests atively low amonger screening rou

o 79 years (12.2nger women. As st in this age ground 1.4 screen-de

BCSC results indicby mammograph

have additional msies5.

at screening mathat would not haherefore would no

nosis varying frome explained variaher cases are inciudies are too hete

f over-diagnosis wy screening in thly randomized tria

a 40% to 60% incdies performed in ng4. s issued from tCanada a and b, on-based programed papers that acancer by mam

mography results 9 years (1.5 per

women aged 70 nd). Biopsy ratesper 1000 womeexpected, the nu

up. Results indicatetected DCIS per cate that for everyhy screening in woammography, 10

ay be defined asave presented clinot be diagnosed i

m less than 1% toations by inclusioident or prevalent

erogeneous to com

was about 30% ihe control groupals before screencrease in incidenAustralia, Europe

the first RCTs Stockholm, Göte

mme (Sweden, Noattempted to est

mmography scree

25

are a 1000

to 79 s are n per

umber te 6.5 1000

y case omen have

s the nically in the

o 30% on or t, and mbine

in the , and ing of

nce of e and

(New eborg, orway, imate

ening.

26

Note that he publications. Bscreened and uand high particcontrol group btime. After excseveral (some being based (definitions of tdescribed befoExcluding DCISaged 60–69 yeaJorgensen anaprogrammes. Hbreast cancer screening. Notehe estimated tscreened popuscreening, he screening withscreened and nmammography for women agebreast cancer Surprisingly, litincidence of bcalculated thatover-diagnosis CI 46% to 58%Discrepancies have led to a loThe approach BZahl, Jorgensewere substantiahypothetical inc

did not include Bias were descriunscreened popucipation in non-scbefore or during foclusion, he selec

overlapping) soon cumulative

terms are in appere, he selected t

S cases, over-detars6. alysed data issHe selected pape

before and afe that when data that they would clation. After exclucompared data

data covering non screened age

screening prograd 70 to 79 years

was closely rettle of this increareast cancer in over-diagnosis foincluding DCIS c)7. between results

ot of controversial Biesheuvel et al. ten and Götzche ally downwardly crease in incidenc

DCIS. He excibed as: differenlation, low participcreening group, oollow up, inappropcted 22 estimatesurces. Publicatio

e-incidence or endix 1.4.3). Excthe least biased otection ranged fro

ued from publicers that publishefter the introduwere present, DC

contribute to 10%usion of the impl

covering at leaat least seven y

e groups. The moammes was 50-6are available. The

elated to the intase was compenwomen older th

for invasive cancecases was 52% in

reported by Biesdiscussions. to adjusting for lea(2008), who statbiased, due to oce based on theo

S

luded potentiallynt breast cancer pation in screeninoffering screeningpriate adjustment s of over-detecti

ons were categorincidence-rate m

cluding biased stuover-detection es

om 7% to 21% for

cly organized scd trends in incidction of mammCIS were included% of the diagnoslementation phasast seven yearsyears after screest common age-r9 years. No data e increase in incidtroduction of scnsated for by a an 70 years. Joer was 35%. Then this meta-analys

sheuvel or by Jo

ad time was conteed that their est

over-adjustment, uretical models an

Screening Breast C

y biased r risk in ng group g to the for lead

on from rized as methods udies as stimates. r women

creening dence of

mography d. If not, ses in a e of the

s before ening in ange for specific

dence of creening.

drop in orgensen e rate of sis (95%

orgensen

ested by imations use of a d use of

locJinstrtoninw2HsinodUsswRTDSccro2uin

Cancer

ong term followconsidered estimaJorgensen & Göncidence with a screening. They arends, following too young to be scnot, the graphs ncidences beforewhom no explanat2.1.3.6. DCIS Historically, DCISsuspicious breasncreasing numbeof the disease is database (SurveilUnited States Nasurvival rate of 9screening was pewhen screening wRecent changes iThis author perfoDCIS in name of She included 63 compared data ocentury data colleose there from 1

2004. Incidence inuse of mammogrncidence8.

w up data that ation unhelpfully wötzsche used line

in an (hypothetassume a linear inhe same pattern creened. It is diffi

the authors pre screening was tion was given.

S was rare and t mass. Since rs of patients werexcellent. Maasslance, Epidemiolotional Cancer Ins96.6% for cases

erformed. The ratewas performed3, 15.

in DCIS incidencormed a SR on

Agency for Heapublications ad

btained before thcted in US where.87 per 100 000

ncreased most in raphy may expla

are considerablywide. ear regression ttical) population ncrease extrapolaas the linear trencult to judge if thiresent show nointroduced in the

diagnosed by sthe wide use

re diagnosed withs reported data isogy and End Restitute). Those das between 1978 e was 98.1% bet

ce in USA were eincidence, treatmlthcare Research

ddressing incidenhe screening (19e screening is com in 1973–1975 towomen older thain some but not

KCE Report

y diluted. They

to compare obsethat did not und

ated from prescrend observed in wois assumption hol

on-linear increasee UK and Norwa

surgical removal of mammograph

h DCIS. The progssued from the S

esults database oata showed a 10

and 1983, whetween 1984 and

emphasized by Vment and outcomh and Quality (AHnce for analysis. 973-1975) with cummon. DCIS incido 32.5 per 100 0an 50 years. Incret all of this incre

t 176

also

erved dergo ening omen lds or es in ay for

of a hy, a gnosis SEER of the 0-year en no 1989,

Virnig. es of

HRQ). She

urrent dence 000 in eased eased

KCE Report 176

2.1.3.7. OveGötzsche repowas significantlrandomization lumpectomies (with suboptima(RR of 1.42 (951.35 (95% CI 1Based on receemphasized ththere were app3500 cases. Aconserving surmethod has remincreasing incidhaving mastect900 in 2007/081

2.1.4. ScreeThe sojourn timdetectable phasimple mathem(mainly Markovthe lead time attainable lead in higher numbgained and high2.1.4.1. LiteIn a first stagMedline was csearch terms Mammography/limited to paperlists of the seleSee more detai

6

ertreatment rted that the numly larger in the sc

showed a sign(Relative Risk (RRl randomization s

5% CI 1.26 to 1.61.26 to 1.44)4. nt data from the e increasing num

proximately 1500 Although, most rgery, the percenmained constant dence of DCIS tretomies has increa11.

ening conditions me (ST) is the avse. Estimation ofmatical estimatev Models)12. Sojou

obtainable. If ttime is correspon

ber of additional her number of yeaerature search e, studies asses

consulted from 19(MESH) were: /. Sojourn time wrs written in Engli

ected studies werels in appendix 1.4

mber of mastectocreened groups. Tnificant increaseR) 1.31, 95% (CI)showed the same1)). The RR for al

UK Breast Screembers of patientscases, but in 200DCIS cases ma

ntage of patientsat 30% during th

eatments, the abssed from just und

verage duration of sojourn time cas or using mic

urn time provides he sojourn time nding long16. A lo

breast cancer dars with cancer du

ssing sojourn tim948 to October WBreast Neoplasm

was included in frish, Dutch, Frence checked for add4.4.

S

omies and lumpeThree trials with ae in mastectomi) 1.22 to 1.42). Tw increase in intervll five trials combi

ening Programmes with DCIS. In 07/08 there were ay be treat by

s being treated wis period. Becaus

solute numbers ofder 500 in 1998/99

of the preclinical an be performed crosimulation tecan absolute uppe

is long, the monger sojourn timedetected, more liue to lead-time17.

me were searcheWeek 1 2011. Thms/ Mass Screeree text. The seach, or German. Reditional relevant c

Screening Breast C

ectomies adequate ies and wo trials ventions ned was

e, Dixon 1998/99 close to breast-

with this se of the f women 9 to over

screen-by from

chniques er limit to maximum e results ife-years

ed. Ovid he main ning/ or

arch was eference citations.

SAc1kEedcreareOscddtwae2SWTeaminsdtoey

Cancer

Selection criteriaAll retrieved refecriteria (in terms o

) in a two-step keywords; followeEstimation of sojexcluding of 3 dudatabases. Of thiscriteria based on etained for full-tex

and 1 did not fetained16, 17, 25-32

Our search was bseveral publicationcited as referencedata published bydata29. Therefore,wo or more artiaccurate for our sextraction table (se2.1.4.2. ResultSojourn times caWe found 4 studiTwo- County Triaestimates of sojouapproximately themodel, but resultsn estimates publisstatistical methodsdeveloped statistico data from the Tearly detection myears (SD, 0.76)27

a erences were asof population, inteprocedure: initial

ed by full-text asjourn time not buplicates, 40 unis total of 40 refetitle and abstra

xt assessment, 6ulfill the outcom

based on ST durans were ST estims by the author. F

y Tabar in 199529

we used originacles based on t

study30, 31. Finally,ee appendix 1.6.7ts

alculated on RCTes based on the

al is described inurn time publishe same data. Both

s were not the samshed by the two as or by discrepanccal methods baseTwo County Trial

modalities as 0.92.

ssessed against ervention, outcom

assessment of ssessment of thebased on data que citations we

erences, 23 did nct evaluation. Am

6 did not fulfill theme criteria24. Fina

ation estimations mations were issueFor example, Zap. Duffy in 200526

al publications. Ifthe same data, 7 publications ar

7).

T’s data results of the Twn chapter 2 (poied by Tabar and h authors used thme. Shen underlinauthors25, 29 may cy in the data. Shed on the maximul. Authors estima

2 (SD, 0.09) and

pre-defined inclmes, and design-Tthe title, abstract

e selected referewere excluded.

ere identified fromnot meet the inclmong the 17 cita population criterally, 10 studies

as search. We fed from others stpa in 200332referrreferred also to one author publwe choose the re summarized in

wo- County Trialint 2.2.1.1.)10, 13. Duffy were base

he same Markov ned that the differbe caused by diffen applied his rec

um likelihood estimated the sensitiviti

the mean ST a

27

usion Table t and

ences. After

m the usion ations ia18-23 were

found tudies red to those ished most

n data

. The First

ed on chain rence ferent cently mates ies of

as 4.4

28

Sojourn times Spratt estimateprevalence rateyears. Thereforincluded in th(Louisville). Forbetween 2.5 y tFracheboud coprogramme for in 1995. Boer use in his MISincrease in prealthough pessimduration with aaged 70-74 yeand subsequenassumption whthe age of 69. strong increasetime17. Weedon constrdo not have fuscreening is cquality, incidenscreening examTherefore, he send to 336 5Programme (Nyears for wome2.1.4.3. DisMost estimatesMarkov chain growth of cancedevelop accordtime must cons

calculated on sced the duration of es at first screeninre, he used data fe Breast Cancer women aged 70to 3.8 y28. ompared the resu

women aged 70-had described o

SCAN model. Opeclinical durationmistic assumptionage33. Based on ars), Fracheboudnt screens increaich assume a coThis increasing

e in detection of c

ructed one inventull registration ofommon. Although

nce data from themination or registrareplaced data la533 women in tBCSP). This new

en aged 60-69 yeacussion s of sojourn timmodels). Such mer. Unfortunately, ding to a chronoequently be interp

creening programbreast cancer be

ng round by incidefrom 10 000 womeer Detection and-74, he estimated

ults of the Dutch -75 with the hypot

optimistic and pesptimistic assumpt

n of breast cancn assumed a furth187 207 screenin

d found that deteased steadily witntinuously increassojourn time of bancers, but also t

ive solution for scf interval cancersh Norwegian rege first screening ation of interval ca

acking by data ishe Norwegian B

w approach gave ars, although STS

e have been bamodels assume a

it remains unknoological sequencepreted with cautio

S

mmes data efore detection by ence rates in the fen aged 35 to 70yd Demonstration d that sojourn time

breast cancer scthesis developed ssimistic assumpttion assumed noer after 65yearsher increase in prng examinationsection rates in both age and got sing sojourn timebreast tumours leto more life- years

creening programs or where oppogistration is of ve

round, interval bancer may be ins

ssued from questBreast Cancer Sc

estimation of MSS was estimated to

ased on Models a chronological s

own whether cance. Estimations of n.

Screening Breast C

dividing following y at start

Project e ranged

creening by Boer tions for o further of age reclinical (women

oth initial close to

e beyond ead to a s in lead

mme who ortunistic ery high between ufficient. tionnaire creening

ST to 6.9 o 60%30.

(mainly stepwise cer really

sojourn

2D

T

Qw

P

In

C

O

M

M

F

F

A

B

Cancer

2.1.5. Key dataData issued from l

Table 2.1: Data is

Question 1: Showomen between

Population

ntervention

Comparison

Outcomes:

Mortality (specifi

Mortality (all caus

FP

FN

Additional imagin

Biopsy

a literature search a

ssued from clinic

ould breast canc70 and 74 years?

Women bebreast canccancer.

Organized

No organiz

c) For womenmortality re23% (RR: County triasignificant r0.92) at 1afterwards.

se) Studies didall-cause m

68.8 per 1screening r

1.5 per 10screening r

ng 64.03 per screening r

12.2 per 1screening r

are summarized in

cal literature revi

cer organized sc?

etween 70-74 ycer and without p

screening with m

ed screening

n >50 y at randoeduction after a fo

0.77, (CI) 0.69 al, specific mortareduction of 27%

15 years of follo.

d not have statistimortality reduction

000 women ageround (BCSC-USA

000 women agedround (BCSC-USA

1000 women ageround (BCSC-USA

000 women ageround (BCSC-USA

KCE Report

n table 2.1.

iew

creening extende

years of age wparticular risk of b

ammography

omization, the spollow-up of 13 yeato 0.86). In the

lity reduction rea(RR: 0.73, (CI) 0

ow up and incre

cal power to dete.

ed 70 to 79 yearA)

d 70 to 79 yearsA)

ed 70 to 79 yearA)

ed 70 to 79 yearA)

t 176

ed in

ithout breast

pecific ars is

Two ach at .59 to eases

ect an

rs per

s per

rs per

rs per

KCE Report 176

DCIS

Over-diagnosi

Over-treatmen

2.1.6. ConclAt this age groadditional imagspecific mortalmortality reducspecific mortaliafter screeningreduction must in our country.On the other pertinent to discin this age-groucancer screenitime bias althoScreening diagthe end of “the diagnosed brea

6

1.4 scre70 to 79

s Over-defrom (7%women a

nt The numwas sig(RR:1.35

lusion oup, performance

ging are relativelyity reduction of tion did not appeity reduction is ng ((RR) 0.80, (Cbe put in perspec

hand, aspects recussion of the benup. First, over-diagng, the risk of o

ough difficult to esnosed breast canlife in good health

ast cancer34.

een-detected DCIS9 years per screen

etection (excludin% to 21%) to 35aged 70 to 79 yea

mber of mastectognificantly larger 5 (95% CI 1.26 to

e of mammograpy low. Breast canc23% to 27% acear in the first yeot statistically sigI) 0.62 to 1.05). ctive with life-expe

elated to quality nefit and harms ognosis being an invertreatment persstimate, may be

ncer and consecuh condition” some

S

S per 1000 womening round (BCSC

g DCIS cases),5% (no data spears are available).

omies and lumpein the screened

o 1.44).

phy is high and cer screening achcording to autho

ears after screenignificant before 1

Breast cancer mectancy for this ag

of life raises qf breast cancer scnevitable consequsists. Secondly, tcrucial for older

utive treatment ma years earlier than

Screening Breast C

en aged C-USA)

ranged ecific for .

ectomies groups

rates of hieves a ors. This ing. The 10 years mortality ge-group

uestions creening uence of the lead women.

ay mean n clinical

22InoessMJliRcTs•••

2Ac2ksdin

Cancer

2.2. Review o2.2.1. Literaturn a first stage, ranon morbidity and meffectiveness of scsources to corresearched35. Medline, Embase,January 2000 up tmited to papers

Reference lists of citations. The keywords usesearch terms (MES Breast Neopla Mass Screeni Mammograph

2.2.2. SelectionAll retrieved refecriteria (in terms o2.2.) in a two-stepkeywords; followeshould be noted digital mammogran KCE report 1722

of modeling studre search strategndomized clinical mortality were seacreening require a

ectly inform deci

, NHS EED and to September 20written in Englishthe selected stud

ed and the resultsSH) were: asms; and ng or Early Detec

hy; and n criteria

erences were asof population, intep procedure: initiaed by full-text ass

that studies assphy) were exclude2.

dies gy trials analysing th

arched (see abova lot of informationsion makers, m

Econlit databases11 (see appendixh, Dutch, French,ies were checked

s are detailed in a

ction of Cancer ; a

ssessed against ervention, outcomeal assessment of sessment of the sessing screeninged because such

he impact of screve). Then, becausn from a wide ranodeling studies

s were consultedx 2.1). The search, Spanish, or Gerd for additional rel

ppendix 2.1. The

and

pre-defined selees, and design - Tf the title, abstracselected referenc

g techniques (suctopic was investig

29

ening se the nge of

were

from h was rman. evant

main

ection Table

ct and ces. It ch as gated

30

Table 2.2: Sele

Population

Intervention

Outcomes

Design

LYG: life-year ga

2.2.3. QuanAfter excluding the databases.citations. Of thicriteria based retained for full15 did not fulfilretained, conceCISNET, 2 appdeveloped by publications17, 3

appendix 2.2.

ection criteria

Inclusion crite

caucasian wombreast cancer particular risk

Screening mam

Morbidity and(e.g. LYG and Q

Modeling studie

ained; QALY: Quality

tity of research a195 duplicates,

. Hand searchings total of 1058 reon title and abs-text assessmentl the design criter

erning 6 models dplications of theseother groups or 36-59. The flow ch

eria Ex

men without and without

OtAs

mmography Otma(e

d Mortality QALYs)

Otdia

es Ot

y-adjusted life-year

available 1058 unique citatg did not allow eferences, 1016 dstract evaluation. t, 2 did not fulfill thria. Finally, 25 modeveloped by mo models on differeauthors, as som

hart of this selec

S

xclusion criteria

ther (e.g. womansian women, etc.)

ther, iammography tec.g. digital mammo

ther outcomes (eagnosis)

ther designs

gained

tions were identifus to identify ad

did not meet the iAmong the 42

he population critodeling publicatiodeling groups invent context and 7

me models have ction is presented

Screening Breast C

n at risk,

ncluding chniques ography)

e.g. over

fied from dditional nclusion citations teria and ons were volved in 7 models

several d in the

T

E

P

In

O

D

22T((cfotodmC(aTcre2eu

Cancer

Table 2.3: Modeli

Exclusion criteria

Population

ntervention

Outcome

Design

2.2.4. Selected2.2.4.1. The CThe Cancer Interhttp://cisnet.canceNCI)-sponsored

cancer control inteor breast cancer. o help determindeveloped their omodeling philosopCenter model37, UMISCAN) model5

and Stanford modThe seven modecontributions of seduction in brea

200077. Mandelblaestimates of poteunder different scr

ing studies exclu

a Studies

Messecar 2

Advisory CAnonymouBonneux 2Koning 20Habbema Rautenstra

d studies CISNET Projectrvention and Surer.gov) is a coninvestigators who

erventions on popThese models are optimal cance

own breast cancphies: The UniverUniversity of Wisc57, Dana-Farber mel51). ls were first usecreening mammost-cancer mortaliatt et all48 used 6ential benefits anreening schedules

uded after full-tex

2000; Wen 20056

Committee on Bus 2000; Barratt 22009; Caplan 20000; Feuer 2002006; Mandelblat

auch 2000, Xu 200

rveillance Modelinnsortium of Natiose focus is moulation trends in i

re also used to prer control strateger models spannrsity of Texas M.consin model, Ge

model44 University

d to assess the ography and adjuity in the United 6 of those CISN

nd harms of mams. One of the 7 mo

KCE Report

xt assessment

0, 61.

Breast Cancer 22002a; Barratt 2001; Carney 2007

04; Grivegnee 2tt 2003; Prevost 20062-76.

ng Network (CISonal Cancer Insodeling the impancidence and mo

roject future trendsgies40. Seven grning a wide rang. D. Anderson Caeorgetown47, Era

y of Rochester mo

relative and absuvant treatment t

States from 197ET models to prmmography screodels, the Univers

t 176

2006; 002b; 7; De 2001; 2000;

SNET) stitute act of ortality s and roups ge of ancer smus odel43

solute o the 75 to rovide ening sity of

KCE Report 176

Texas M. D. Apurely descriptiThe models wethey were comprocess, they aUS datasets B(Surveillance, eand the BerkeleA detailed dispublications anddetail, but sumdiscuss the maThe models espresent the recomparison of policy screeningFeuer et al.40

surveillance mosimulation modthrough the mnumber is gemechanistic orequations desctumor growth aCancer Centermodels could Farber model cmodels (Univehaving some characterizationobservable quaprogression of disease procesThe models statrends without screening use a

6

Anderson Cancer ve. ere developed by

mpared, discussealso used a commBCSC (Breast Caepidemiology andey mortality Databscussion of eachd on the CISNET

mmarize the pooleain limitations anstimated a large

esults of the parta screening pol

g age 50-74. identifies two d

odels used heredels at one end oodel one at a tinerated and indr analytic modelcribe the relationand metastasis. Tr, University of be characterizedcould be charactersity of Rochesteaspects of ea

n runs from bioantities to model t

disease, to epids is modeled (usuart with estimatesscreening and t

and improvements

Center model37

y different grouped and adapted mon set of variabancer Surveillancd end results), Cobase. h of this modelswebsite, we will n

ed comparison ofnd implications foe number of scet relevant to ourlicy screening ag

dimensions to ch. The first dimen

of the spectrum, wime, where at edividual life histols, where a set

nships between kThe University ofWisconsin, Geo

as micro simulaerized as analyticer and Stanford)ch. The secondologic, where ththe underlying disdemiologic, wherually the observabs of breast cancetreatment and ths in survival assoc

S

was not used as

s but not indepeduring the deve

bles and inputs, bce Consortium), Sonnecticut Tumor

s can be foundnot discuss each mf Mandelblatt et aor our research qenarios, but we wr research questge 50-69 to a sc

haracterize the tnsion incorporatewhere individuals ach transition a ories are generat of analytically key health statesf Texas M. D. Aorgetown, and Eation models; thec; and the remain) could be descrd dimension ofhe model goes sease onset, growre only a portionble portion). er incidence and mhen look at the eciated with treatm

Screening Breast C

s it was

endently, elopment ased on SEER 9 r registry

d in the model in al.48 and question. will only tion, the creening

types of es micro

are run random

ated, to derived

s and/or Anderson Erasmus e Dana-ning two ribed as f model

beyond wth, and n of the

mortality effect of

ment.

BpmdidceinoaccasthgTmmmwbotedredpTreligdTmIn

Cancer

Breast cancer is period (sojourn tmammography sedisease in the prdentification of eaclinical detection, estrogen receptor ndependent effecother causes. as age-specific variacharacteristics, trecompeting causesas preclinical detestages of diseasehat followed fromgrowth. The stage distribumodels were alsomodels that use thmodel reductions were used. The habiopsies and overobserved input waerms of QALYs. Mdisease or decreesults living with

diagnosis was notpurposes. Table 2.4 gives teduction and yeamited and there

gained per 1000 deaths averted ranThis class of modemodels are indivndependent valid

assumed to haime) and a clin

ensitivity (or thresreclinical screeninarlier-stage or sm

resulting in redustatus, and tumo

cts on mortality. Wmentioned before

ables for breast eatment algorithms of death. On theectable times (soje, were in these the model struct

utions in unscreeo intermediate ouhis observable vain mortality, life yearmful effects falsr diagnosis followas used, no attemMorbidity associa

ements in qualityh earlier knowlet considered, whic

he results of thears of life gained f

is some variabilitwomen screenednging from 4 to 6.els relies heavily ovidual bases theation was made

ave a preclinical,ical detection poholds of detectionng-detection perioaller tumors than uction in breast cr size– or stage–sWomen can die oe, the 6 models cancer incidence

ms and effects, a other hand, unobourn time), lead models estimatedture and assumpt

ened versus screetcomes, this in c

ariable as input. Aears gained werese positive mamm

wed from the modpt was made to q

ated with surgery y of life associatedge of a cancech makes the mod

e different modelsfor the different mty between moded ranging from 9

on unobservable vey are not alwadifficult because

, screening-detecoint. On the basn), screening idenod and results i might be identifiecancer mortality. specific treatment of breast cancer use a common s

e, mammographyand non-breast cabserved variablestime, dwell time wd intermediate outions concerning t

ened women in tcontrast to some As end output frome calculated, no Qmograms, unneceel, also here no

quantify those harfor screening-detted with false-poer diagnosis or dels less useful fo

s in terms of momodels. Gains are els, with number

to 17 and numb

variables, and as ays very transparesults from trials

31

ctable sis of ntifies n the ed by Age, have or of

set of y test ancer such within utputs tumor

these other

m the QALYs essary direct

rms in ected

ositive over

or our

ortality fairly

years ber of

most arent. s and

32

the main US calibrate the mand some obsvalidity of the calibrate the mo

Table 2.4: resreduction and different mode

Model group abbMedical Center; G_Stanford Univer

Stout et al 200analysis, includ50-74 with age Rue et al.55 adZeelen44 to daton Catalan survUS with CatalObtained resulfound, a morta

ModelMortality (specific) reperiod in %Screening in agegroup Screening in agegroup Incremental mortality reagegroup 50-74 compaagegroup 50-69Years of life Gained pscreenedScreening in agegroup Screening in agegroup Incremental years of lifagegroup 50-74 compaagegroup 50-69 Incremental days of liscreenedScreening in agegroupscreening in agegroup

breast cancer rmodel. Model outp

ervational studiesmodel as data

odel.

sults of the di years of life ga

els

breviations: D _ DanG _ Georgetown Unrsity; W _ University

0656 used the Wisding the use of QAgroups 50 - 69 w

dapted de Dana-Fta in Catalonia. Bvival they combinan data in a prts were very sim

ality reduction of

eduction over the whole

50-69 50-74eduction screening in ared to screening in

per 1000 women

50-69 50-74fe gained screening in ared to screening in

ife gained per women

p 50-74 compared to 50-69 women screened

registries were uputs are similar tos, but this does from those stud

ifferent models ained per 1000 w

na-Farber Cancer Inniversity; M _ M.D. Ay of Wisconsin/Harv

sconsin model toALYs, but compaere not made. Farber Cancer InBecause there waned the survival darevious publicatio

milar to the ones 21% and 131 life

D E G

16 23 1722 27 21

6 4 4

88 107 111106 116 128

18 9 17

6,6 3,3 6,2

S

used to parameto the results fromnot say much ab

dies were partly

in terms of mwomen screened

nstitute; E _ ErasmuAnderson Cancer C

vard

o do a cost effecarisons of the age

stitute model of Las insufficient infoata from the SEE

on of Vilaprinyo, Lee & Zeelen o

e years gained p

M S

16 1521 20

5 5

82 9996 121

14 22

5,1 8,0

Screening Breast C

erize or m RCT’s bout the used to

mortality d for the

us Center; S

ctiveness e groups

Lee and ormation

ER in the 200958.

originally per 1000

winmhqCaTbbTbbcesgdco2CgbthsskRDbjureG

W

2328

5

8495

11

4,0

Cancer

women screened ncremental benefmortality and 2 lifhad no choice thquestion in what Catalan context. Cand Vilaprinyo et aThey found 3990 biannual screeningbiannual screeninThey found 3891 biannual screeningbiannual screenincompared to a schextending the scrscreening from 45gained by extendindid not incorporacalculations, but uover diagnosis. 2.2.4.2. ModelCarter et al, 20053

growth using mainbecause of unreahey assume a fixstages 1, 2 and 3.screening than otknow about stage Rojnik et al, 2008 DCIS, local, regiobut details on howudge how this waeport ICERs so w

Gained and QALY

for a biannual scrfit for biannual sfe years gained phan to use US degree this can

Carles et al, 2011al58 to do a cost elife years gained

g in the age groug 50- 74 of 299 QALYs gained g in the age groug 50- 74 of 277 hedule 50-69. Thereening to 50-74 5- 69, but reporteng the screening ate the results used US survival

ls not related or 39, 78 developed a nly SEER data. Thlistic assumptions

xed survival of 2 y This leads to con

ther models but ispecific survival.produced a time d

onal and distant.w the model was pas done or if asswe have no informYs.

reening in the agescreening 50- 74per 1000 women data for most kereally be called

138 finally used theffectiveness anald for a cohort of p 50-74, with an life years gainedper 100 000 wop 50-74, with an life years gained

ey did not report tfrom 50 -69, as

ed that 186 QALto 45-74 from 45 of Vilaprinyo et

l data. They did

not using CISNEmicro simulation he model lacks crs concerning stagyears for stage 4 nsiderably higher s in absolute con

dependent MarkoOverall model stparameterized aresumptions were rmation on assum

KCE Report

e group 50-74, w4 of 1.7% in term

screened. As auey variables one

an adaptation the results of Rueysis, including QA100 000 women incremental bene

d per 100 000 woomen screened wincremental bene

d per 100 000 wothe QALYs gaineds it was dominateLYs per 100 000

-69. Interestinglyt al,200958 into not take into ac

ET methodologymodel based on tredibility though mge specific survivaand complete cuyears of life gainentradiction to wha

ov model with 4 structure was desce lacking so we careasonable. Theyed gains in Life Y

t 176

ith an ms of uthors e can o the et al ALYs. for a

efit for omen. with a efit for omen d with ed by were

, they their

count

y tumor

mainly al, as re for ed for at we

ages, cribed annot

y only Years

KCE Report 176

Neeser et al dscreening with coverage of 20breast cancer munclear how thranging from 5 years screeninrelevant for ouscreening wouldays) per womsimplistic by nreductions immwas not taken iRauner et al, 2only evaluated rather experimehow they actuaMahnken et al,length bias andonly adjusted HRijnsburger et developed by tCanadian CNB50–59, so their Barratt et al 2cohorts, with oother not, assuthe outcomes oscreening. Thereduction fromlinearly to maxthat benefit descreening. For of 70s, two fewwomen who stonumber of diag

6

developed a sima coverage of

0%. They assummortality with 15%hey come to this

to 20%. They cang beginning at ur research quesd save 41 lives p

men screened for not taking into amediately. No QAnto account.

2010 developed athe effect of scr

ental model is notlly modeled stage, 200846 develope

d over-detection aHazard ratio’s.

al, 200453 usethe Rotterdam57 SS-2 trial on breafindings are not r

200536 constructeone cohort womeming 100% partic

of women over 70ey assume a 37% for non compli

ximal level over fieclines linearly towomen who cont

wer women per op screening (sixnoses of breast c

mple Markov mod70% with opported that the orga% based on the s figure as IARCalculated the yea70 (they evaluat

stion as well. Thper 100 000 and 10 years. The mccount lead time

ALYs were used

an ant colonizatioreening amongst t useful for our pue specific survival.ed a method to and applied this to

ed the MISCAN (see above) to rast cancer screenreally useful for oued a Markov moen undergoing biecipation. Within th

0 years old underg% mortality reducance, and assumrst five years afteo nothing over ftinue screening fothousand die fro

x v eight deaths fcancer in screene

S

del comparing ortunistic screening

anized screening IARC handbook,

C postulates a rears of life gained ted other scheduey found that oradd 0.008 life ye

model is somewhae but applying aand effects on m

on optimization mwomen 50-70 a

urposes. It is also. adjust for lead timSEER data, but p

micro-simulationreplicate the dataning among womur purposes. odel for two hypennial screening his model, they evgoing 10 years of ction, adjusting tme that benefiter starting screenfive years after sor 10 years after m breast cancerfrom breast cancd women is abou

Screening Breast C

rganizes g with a reduces but it is

eduction for a 10 ules not rganized ears (2.9 at overly assumed morbidity

odel but and their o unclear

me bias, provided

n model a of the en aged

othetical and the valuated biennial

the 25% accrues

ning and stopping the age than in

cer). The t 41 and

th5Tin2Matoli

2BimdinhTaeafoDre1

Cancer

he number in uns50% brings the nuThis simple modento account the ef2.2.5. ConclusiModels described adapt them to the o parameterize thfe between 9 an 2

2.3. Review oBecause breast cmpact on the qudimensional healthnformative. It is health outcomes iTo value these madjusted life-year expected length adjustments are mor different healthDetermination of equires two steps. The health s

guidelines of health statessystem. Idealusing a genestates descrdescriptions fr

screened women umber of deaths el has the advantaffects of lead timeion are give useful inBelgian situation

hem. The CISNET22 years per 1000

of quality of life cancer screening

uality of life (QoLh-outcome measuimportant to taken the assessmenultidimensional ou

(QALY) must bof life by the

made using utilitieh states.

utility values, ns: tate description.

f the Belgian Hes should be deslly, the descriptioeric descriptive sriptions from Brom similar patien

about 26. assumin the screened gage of transparen

e and stage-shifts

nsights and elemen as we do not haT models give a m0 women screene

studies g programs are L) of the patientsure in terms of sue into account alnt of breast canceutcomes into a sibe used. QALYs

health-related qes derived from i

eeded for the c

According to theealth Care Knowscribed on a staon should be donsystem, such as Belgian patients nts in other countr

ming a risk reductigroup down 6.2 toncy, but does noton morbidity.

ents but it is difficave the necessarymodest gain in ye

ed.

expected to havs, models with a urvival are not enl the multidimens

er screening progrngle measure, qupermit to adjus

quality of life. Tindividuals’ prefer

calculation of QA

e pharmaco-econwledge Centre (Kandardized descrne by Belgian pa

the EQ-5D. If hare not avai

ries may be used7

33

ion of o 5.1. t take

cult to y data ear of

ve an one-

nough sional rams. uality-st the These rence

ALYs,

nomic KCE), riptive atients health lable,

79.

34

2. The valuat

economic gon a 0 (=vrepresentavalued by collected, discussed7

In this section,describing the treatment) is as2.3.1. Metho2.3.1.1. LiteElectronic dataestimates for screening and end of OctobeEmbase (via E(via OVID). Searches usingheading or texstrategies and t2.3.1.2. SelIdentified refere(in terms of poptwo-step procedfollowed by fuabstract was acitation was asthe selected stu

tion of these heguidelines of the Kvalue for death) toative sample of th

the Belgian popuvaluations from

79. the availability aburden of disea

ssessed. ods erature search stabases were con

different health treatment. System

er 2011 in the fombase.com), HTA

g various qualifierxt word. See appterms used. lection criteria ences were assespulation, intervendure: initial assesll-text assessmen

available and thesessed based on

udies were scrutin

ealth states. AccoKCE, health stateo 1 (=value for phe general publiculation but if no

m other countrie

and the quality oase due to breas

trategy nsulted for origin

states associatmatic searches wollowing databasA and EED (via

rs for “quality of lipendix 3.1 for an

ssed against pre-tion, outcome andssment of the titlent of the selecte

e citation was unn keywords and funized for additiona

S

ording to the phe values should beperfect health) scac. Ideally, they shoriginal Belgian des can be use

of published utilityst cancer (screen

nal publications oted with breast

were carried out uses: Medline (viaCRD NHS) and P

fe” were used asn overview of the

-defined selectiond design –Table 2e, abstract and keed references. Wnclear or ambiguoull-text. Referenceal relevant citation

Screening Breast C

armaco-e valued ale by a hould be data are ed and

y values ning and

on utility cancer

up to the a OVID), Psycinfo

Subject e search

n criteria 2.5) in a eywords;

When no ous, the e lists of

ns.

T

P

In

O

D

QQeHa

Cancer

Table 2.5: Article

I

Population Spcor

ntervention At

Outcome Ua(

Design Do6ms

QoL: Quality of Life. Quality of Life. DALYequivalent; TTO: TimHUI: Health Utility Inanalysis. VAS: visua

selection criteri

Inclusion criteria

Screened or treatpatients for breascancer, with a Caorigin and withoutrisk factors

Any intervention rto the Belgian set

Unique QoL weigallowing to derive(=utilities)

Direct (TTO, PTOor indirect (EQ-5D6D, HUI, QWB) vamethods in primastudies

QALY: Quality adjuY: Disability-Adjusteme-Trade-Off. PTO:ndex. QWB: Quality al analogue scale

ia

a Exclus

ted t ucasian t high

Other dCauca

relevant ttings

InterveBelgium

hts QALYs

Multi-dscores

O, SG) D, SF-aluation ry

LettersCUA wfrom thDirect (not reKCE pguideli

usted life year. HRQed Life-Years. HYE: : Person Trade-Off. of Well Being scale

KCE Report

sion criteria

diseases, non sian, high risk wo

entions not used inm

dimension HRQoLs, DALYs, HYEs, …

s, secondary studiwith QALYs derivehe literature, … valuations using Vcommended in thharmaco-economnes)79.

QoL: Health-Related healthy-years- SG: Standard-Gam

e. CUA: cost-utility

t 176

omen

n

L …

ies, ed

VAS e

mic

d

mble.

KCE Report 176

2.3.1.3. SelThe flowchart osearches on thduplicates, 352searching allowninety (290) ref65 references fat this stage, mOverall, we sele2.3.2. ResulA summary of tbe noted that values and theireported in the The selection o• Determinat• Selection o

Selection oSelection o

• Pooling of 2.3.2.1. DetHealth states foIt should be noreflection proce

6

lection process of the selection p

he databases retu2 unique citationswed us to identifyferences were disfor full-text evaluamostly because ofected 16 primary slts the selected studithis summary onr results. If other summary.

of utilities was dontion of health stateof utilities of a basecase studof other studies selected utilities atermination of heor which utility valuoted that this figess but not the

process is presenurned 524 citations were left (see ay 3 additional citacarded based on tion. Another 49 rf the unmet desigstudies (see appe

ies can be found nly report methoparameters were

ne according to thees for which utilitie

dy

and calculation of ealth states ues are needed a

gure is a schemamodel itself (de

S

nted in appendix 3ns. After exclusionalso appendix 3.2ations. Two-hundtitle and abstract

references were egn and populationendix 3.2).

in appendix 3.3. Iods used to deriv

measured, they w

e following stageses were needed

percentage chan

are listed in Figureatic representationescribed in secti

Screening Breast C

3.2. The n of 172 2). Hand dred and , leaving excluded criteria.

It should ve utility were not

s:

ges

e 2.1. n of the on 3.2).

Cancer 35

KCE Reports vo

Figure 2.1: Hea

Women ag

Before

ol

alth states for wh

ged ≥ 70 years

e screening

hich utilities are

Positive

Negative

False p

True po

Short termof the sc

S

needed (reflecti

results

e results

positive

ositive

m impact reening

Screening Breast C

on process)

Metas

Women aged

Breast cance

Breast cance

Breast cance

After scre(First y

Non me

Breast canc

Cancer

static

≥ 70 years

er stage II

er stage III

er stage IV

eeningyear)

etastatic

cer stage I

Women

Breast

Breast

Breast

Aft(Foll

No

Breast

Metastatic

aged ≥ 70 years

cancer stage II

cancer stage III

cancer stage IV

er screeninglowing years)

on metastatic

t cancer stage I

36

KCE Report 176

2.3.2.2. SelTo select utility by the pharmacdata could be foThen, we triedmodel. The aiminstruments andthe pharmaco-eto use the samquality of life weHowever, no st2.3.2.1 with thestudy with the gand to use it at Selection of thWe found onlymetastatic and the chance thaccording to th5D79. This studyUtility values imethods, i.e. technique) by Sgeneric instrumeconomic guidethese valuationTTO). In this stvalued using UKavailable). Heavalues for nontreatment) and patients are desThis study had

6

lection of utilities values, we first tco-economic guidound. to find the mos

m was to avoid d multiple populaeconomic guidelinme descriptive inseights coming fromtudy assessing ae same design wgreatest number othe starting point

he base case stuy one study havimetastatic patienat this study als

he pharmaco-econy was therefore thin the study of a direct valuatioSwedish patients ment (i.e. the Eelines of the KCEs were retained (tudy, health statesK tariffs (because

alth states descri-metastatic patiethe following yea

scribed in Table 2the following limit

s tried to find Belgiadelines of the KCE

st complete studyas much as pos

ations to derive thnes of the KCE, it strument and them different studiesll of the heath sta

was found. We thof health states coof the selection pdy ing assessed uti

nts, i.e. the study oso used the betnomic guidelines he starting point oLidgren et al.80

on method (i.e. and an indirect v

EQ-5D instrumenE recommend thei.e. utility values fs were described

e no tariffs from thptions can be fonts in the first yars as well as ut2.8. tations:

S

an data as recomE79. However, no

y which best fit wsible the use of em. Indeed, accois strongly recom

e same set of vas79. ates described inherefore tried to orresponding to ouprocess.

lity values for boof Lidgren et al80.tter available insof the KCE, i.e. f our selection prowere derived fr

the time-trade-ofvaluation method nt). Because phe use of the EQ-5from EQ-5D and by Swedish patiee Swedish popula

ound in Table 2.6year (i.e. the yeaility values for m

Screening Breast C

mmended Belgian

with our multiple

ording to mmended alues for

n section find the

ur model

oth non-We had

strument the EQ-

ocess. rom two ff (TTO) using a

armaco-5D, only not from ents and ation are 6. Utility

ar of the etastatic

•

•

•

Cancer

Utility values cancer outpatfollowing limitaUtility values f

the shortthis shorttime and

Utility values palliative only reflefirst year

The short term(not measthis studythe valua

Non-metastatyear of diagnthat after the assumption idifference in uyear 5, 10 and

It should also (primary breapatients werinconstistencyMetastatic p

consultatGeneric instru

relevant specific ionly be uthese ins

were measuringtient clinic (Karolations: for non-metastatict term impact of st term impact wawas therefore notfor metastatic p

care. It was therected the quality of diagnosis.

m impact of diagnsured at the momy reported that thisation (measured thtic patients were dosis and the folloyear of treatmenis supported by utility values (fromd 1581. This US stbe noted that util

ast cancer in the re similar (0.6y may be due to thpatients only incions (best cases)uments such as tchanges in healtinstruments. How

used if validated mtruments are avai

g during out-patieinska University

c patients did not surgery. Howevers expected to cot included in the mpatients did not refore assumed thof life of metasta

nosis is also not fment of the diagnos impact was exphe year of diagnosdivided in only twowing years. It wt, utility values re

an US study m EQ-5D using Utudy is described ity estimates for nfirst year of diag96 and 0.685 he following reasoclude patients . he EQ-5D are lesth in a specific d

wever, diease-spemapping functionsilable, which was

ent visits at a bhospital), implyin

fully take into acr, on an annual b

over a limited lengmodel.

represent patienhat these utility v

atic patients durin

fully taken into acosis), even if authoected to be includsis). wo groups, i.e. thewas therefore assuemained constant

where no signiUS tariffs) was fou

in the appendix 3non metastatic pagnosis) and meta

respectivelly). ons: going in out-p

ss sensitive to cadisease than diseecific instrumentss to derive utilitiesnot the case79.

37

breast g the

count basis, gth of

nts in values ng the

count ors of ded in

e first umed . This ficant

und at .3.

atients astatic

This

atient

apture ease-s can s from

38

Table 2.6: Hea

Primary bcancer (year 0

Recurrence (y1)

Primary bcancer recurrence following year

Metastatic patSelection of otFor other heainstruments for us to identify apopulation stratwith UK tariffs),therefore used For the short tusing the EQ-5assessed utilitytrue negative. Hthe Swedish postates (as in positive” state is

lth states descri

breast -1)

Patients cancer wquestiondisease

year 0- Patients regional prior to metastat

breast and

rs

Patients breast cayear priometastat

ients Patients ther studies lth states, we trthe same popula

a study assessintified by age and , i.e. the study of for women aged 7term impact of p5D instrument way values for false Health states wereopulation) but UKthe other selects given in Table 2

ptions for the st

who had primawithin 1 year or lennaire, no recurre

who had at leaand/or contra-lateanswering the

tic disease.

who had been dancer or their lasor to answering thtic disease.

who had metasta

ried to find studation. The study ong utility values gender using the Burström et al.82

70 and over (see positive results afas identified (Gepositive, true po

e described by thK tariffs were usedted studies). A d2.7.

S

udy of Lidgren e

ary diagnosis bress prior to answeence and no m

st one recurrenceral) within 1 yea

questionnaire,

diagnosed with a t recurrence morehe questionnaire,

atic disease

dies having usedof Lidgren et al.80

for the general Ssame instrument These utility valuTable 2.8).

fter screening, onrard et al.)83. Thsitive, false negae UK population d to valuate thesdescription of th

Screening Breast C

et al.

reast of ering the etastatic

ce (loco-r or less and no

primary e than 1 , and no

d similar allowed

Swedish (EQ-5D

ues were

ne study his study ative and (and not e health e “false

Ainreoaareufawthd•

•

•

UIt3cpDCc•

Cancer

As showed in thisnvited for screenecalled for furth

obtention of a dassessment, only activity; pain/discoemaining two di

unaffected. The qalse positives laswere measured fherefore not be udecided to make th True negativ

population. The short term

the percentag This impact is

screening accet al.82 (generet al.80 (non mwere used.

Utility values for fat should be noted3.3 assessed the complexity and bepositive” in the stuDomeyer et al.84 inConcerning the evcancer in the long

s table, the descrining, having a brher examinationiagnosis, i.e. nothree of the five E

omfort; and anxietmensions (i.e. m

quality of life effecsted 12 months for the remainin

used to measure the following assu

ve patients have

m impact of positge change betwees present until the cording to IMA daral population for metastatic or met

alse positive and t that the study of short term impa

ecause the biopsyudy of Gerard et anto account. volution of utility vterm, no study wa

ption include the reast screen, wais, having furthe

o evidence of brEQ-5D dimensionty/distress and it

mobility and abilcts associated wwhile true positivg life expectancthe short term immptions:

e utility values e

ive results at screen true negative a

diagnosis, i.e. onata. After, either v

false positive) ortastatic disease y

true negative can Domeyer et al.84

ct of biopsy. Howy is included in theal.83, we decided t

alues for patientsas found.

KCE Report

following stage: iting for results, er examinations reast cancer. Fos were used, i.e. was assumed thaity of self-care) ith true negativesve and false neg

cy. These valuesmpact of screening

equal to the ge

eening is measurend false positive.

n average 45 daysvaluations of Bursr valuations of Lid

year 1 for true po

be found in Tabledescribed in app

wever, to avoid me description of a to not take the stu

s with metastatic b

t 176

being being

and or the usual at the were

s and gative s can g. We

eneral

ed by

s after ström dgren

ostive)

e 2.8. pendix model “false

udy of

breast

KCE Report 176

Table 2.7: Des

Routine breast

Further tests

The results of are ready wweek

Quality of life eroutine screening (sho

Receiving invitation

Waiting for ththe appointme

6

cription of a “fal

t screen • S• T• T• A• T

c• S• O• T• T• T• T• F

bthe tests

ithin the • T

effects of breast

ort term)

The Qconti

the • M• S

he day of ent

• M• S

c• P

lse positive” stat

She is invited by lThe appointment The visit at the breA female radiograTo take the X-raycompressed to geShe is asked by leOther tests are neThis visit may takeThe breast X-ray The doctor examiThe doctor may cFluid from the affebetween the X-rayThe tests show no

QoL of some womnue for some time

Most women are Some women are

Most women carrySome women arecarry on with theirPersonal and sex

S

te (Gerard et al)8

etter for routine bis about 2 weeks east screening ce

apher asks about ay she is asked to et the best possibletter to go to the beeded because the up to half a dayis repeated. nes her breasts.arry out an ultrasoected area is takey plates. o evidence of brea

men is affected bye.

pleased to receivee made nervous, a

y on with their usue anxious and depr usual activities aual relationships m

Screening Breast C

3

breast screening.from receiving the

entre takes about any symptoms or undress to the w

le picture. breast screening ce breast X-ray res.

ound examinationen for laboratory a

ast cancer.

y the experience

e the invitation. anxious or depres

ual activities and ipressed, unable toand interests. may be affected.

Cancer

e invitation. half an hour, whichistory of breast

waist. Each breas

centre the followinsult is not clear.

n. analysis using a fin

of routine breast

sed, and are worr

interests. o concentrate, sle

ch may include wadisease and explat is placed in turn

ng week.

ne needle to do th

screening and br

ried about having

ep badly and are

aiting time. ains what will hapn between two sp

his her breast may

reast cancer diag

breast cancer.

moody and irritab

ppen. pecial X-ray plates

y again be compre

nosis. The effects

ble. They are una

39

s and

essed

s may

ble to

40

At the breast sclinic

Waiting for the

Clear results test

Table 2.8: Des

Author (year)

Lidgren et al. (2007)80

Burström et al. (2001)82

Gerard et al. (1999)83

screening • M• M• M• M• S

e results • M• S

t• PIf rec

• M• O

after the • M• S

cription of the se

Instrument Pd

EQ-5D

S(

EQ-5D S(

EQ-5D Wy

Most women are Most women are Most women are Most women find Some women findMost women carrySome women areto carry on with thPersonal and sexcalled for further te

Most women are vOne of the tests, wMost women are Some women rem

elected utilities

Population for hedescription

Sweden patients(Mean age: see h

Sweden patients(Mean age: see h

Women from UK ayears (eligible for

S

nervous, but are nnot embarrassed not unduly worriedthe breast X-ray i

d the breast X-rayy on with their usue anxious and depheir usual activitiesual relationships oests:

very anxious at bewhere the doctor reassured by the

main anxious for u

ealth state Po

ealth states)

UK

UK

UK

ealth states) UK

aged 40-64 screening) UK

Screening Breast C

not anxious or depby the screening d about breast cais uncomfortable a

y very uncomfortabual activities and ipressed, un-able s and interests. of some women m

eing recalled for fremoves fluid fromclear results.

up to a year before

opulation for valu

K tariffs (general p

K tariffs (general p

K tariffs (general p

K tariffs (general p

K tariffs (general p

Cancer

pressed. procedure.

ancer developing.and slightly painfuble and painful. interests. to concentrate, s

may be affected.

urther tests. m the affected are

e they are back to

uation Hea

population) Prim

population) Brea

population) Meta

population) WomWomWom

population) True

ul, but this is short

leep badly and ar

ea, is painful.

o their usual self.

alth state

mary breast cance

ast cancer (follow

astatic patients; M

men aged 50-59men aged 70-79men aged 80-88

e negative

t lived.

re moody and irrit

er (Year 0-1); Mea

wing years); Mean

Mean age 56

KCE Report

table. They are u

Meavalu

an age: 56 0.69

age: 58 0.77

0.68

0.830.790.74

0.94

t 176

nable

n ue

6

9

5

3 2 0

0

KCE Report 176

2.3.2.3. Poo

chaA summary of can be found inal.82 were chos(A)). These valchange relativepercentage chaThe next stageassumed that uvalues in the gutilities betweecalculated, i.e.negative womeafter screening utilities will be m

6

oling of selectedanges selected utilities n Figure 2.2. Theen as the initial vues varied accord

e to these valuesanges did not varye concerns the shutility values for tgeneral populatioen true negative -16% (B). Initia

en and decreased(false or true pos

maintained for 45

d studies and cal

and of calculatioe utility values of alues of the modeding to women ag

s was applied. It y according to the hort term impact true negative wom

on (A). Then, the women and fal

al values were td by 16% for womsitive). As mentiondays.

S

lculation of perc

n of percentage cthe study of Burs

el (first state of thge. Then, the perwas assumed thwomen age (no dof the screening

men were equal percentage decr

se positive womthus maintained men with a positivned in the section

Screening Breast C

entage

changes ström et

he model rcentage at these data). g. It was to utility rease in

men was for true

ve result 0, these

Fvoscwb(Fn1pcth(

Cancer

For the first year values equal to thof the study of Lidstudy of Lidgren changes between women aged 50-5by 16% ((0.696-0.(0.685-0.833)/0.8

For the next yearnon-metastatic or

6% (C) and 18%patients who staycompared to the ghe years after (DG).

of screening, wohe general populadgren et al. wereet al.80 and the values for the sa

59 (and UK tariffs.833)/0.833) for n33) for metastaticrs, people from tmetastatic breas

% (E) respectivelyyed in this staggeneral populatio

D). Metastatic pat

omen without breation (A). For true used.80 To makestudy of Burström

ame population ws). Utility values wnon metastatic pac patients (E). the general popust cancer had utiy (as calculated age had their utilin ((0.779-0.833)/0ients maintained

east cancer had e positive, utility ve the link betweem et al.82, perce

were used, i.e. Swwere therefore redatients (C) and by

ulation who develity values reduce

above). Non-metaity decreased by0.833) and mainttheir utility until d

41

utility values en the ntage

wedish duced y 18%

loped ed by

astatic y 6% ained death

42

Figure 2.2: Per

Women age

Before

rcentage change

ed = 70 years

e screening

A

e in utilities

P

Short termscreeni

S

Positive results

True negative

False positive

True positive

m impact of theing (45 days)

B

A

Screening Breast C

Wome

Brea

Brea

A

N

Brea

Brea

Cancer

en aged = 70 yea

ast cancer stage II

ast cancer stage II

After screening(First year)

C

A

Non metastatic

ast cancer stage I

Metastatic

ast cancer stage IV

F

rs

I

I

VMetastatic

Women aged = 7

Breast cancer st

Breast cancer st

Breast cancer st

After screeni(Following yea

F G

C D

A

Non metasta

Breast cancer s

KCE Report

c

70 years

tage II

tage III

tage IV

ingars)

E

atic

stage I

t 176

KCE Report 176

2.3.3. DiscuTo include thevalues for eachthis chapter waon the KCE phamultiple instrumderived from the• The analys• No Belgian

possible (nUK tariffs results, Be

• The short taccount be

• Even if thethese utilitithis instrumConsequensuch as aimportant instrument low percenwomen in metastatic specific insbecause th

• Finally, thebetween reappendix 3parametersthese para

6

ussion quality of life im

h health state of tas therefore to searmaco-economic

ments and multiple EQ-5D instrume

sis had the followin data were availano access to priminstead of Belgialgian data would bterm impact of su

ecause no valid dae EQ-5D is one oies (according to ment is less senntly, it can be expa mastectomy (pif a disease sphad been used.

ntage change bethe general pop

patients. The assstruments was nehese instruments de review of the eported utility esti3.3), revealing as. Because of thmeters should be

mpact of screeninthe model had to lect these valuesc guidelines79. Wee valuations and ent. ng limitations: able and a transf

mary data). Even ian valuations wobe interesting for urgery and of diagata were availableof the best availathe KCE pharma

nsitive than diseapected that the impartial or total) pecific instrumen This lack of senetween patients pulation or betwsessment of the qevertheless not indo not permit to dliterature showedmates for breast

a high level of uhis uncertainty, a

e done in the chap

S

ng in the analysibe identified. The. The method wae tried to avoid th

focused on utility

ferability analysis if we expected th

ould not greatly infuture models. gnosis was not tae. able instrument toaco-economic guidase specific instrmpact of some cowould have bee

nt instead of a nsitivity could expwith breast caneen metastatic a

quality of life from vestigated in this erive QALYs.

d an important vcancer health sta

uncertainty arouna sensitivity ana

pter on model resu

Screening Breast C

is, utility e aim of

as based e use of y values

was not hat using nfluence

aken into

o assess delines), ruments. onditions en more

generic plain the cer and and non disease chapter

variability ates (see nd these lysis on

ults.

3TsacbwWthsnfiUWththbuh••

•

Cancer

3. DECISIOTo quantify whatsituation we consapproaches. For cancer registry anbelow). For the sewith annual cyclesWe consider perfohan trying to adasituation. Indeed, not available andindings of these mUS) data. We look at the effehe currently existhe current level. Tbaseline without huse of an additionhere: Available data Additional lite

screening and The model us

ON ANALYt the implicationsstructed a decisiothe first simple

nd data from the lecond, we constr

s. orming one Belgiaapt the models dBelgian data nee

d we would memodels, as we wo

ect of introducing ing situation with This has the advahaving to modify nal number of no

a used in this decierature review focd to the breast cansed for this decisio

YSIS s of our findingson analysis modapproach, we apliterature on the Bructed a simple t

an decision analydiscussed in chaeded to parameterely reproduce t

ould be obliged to

mammography sthe opportunistic

antage that we cathen, as this can

on verifiable assu

ision analysis; cused on qualityncer as such; on analysis.

s are on the Beel using two diff

pplied data from Belgian life tablestime dependent c

ysis a better apprapter 2 to the Beerize these modelthe already publo use the same (m

screening in additscreening going

an use Belgian da only be done m

umptions. We des

y of life related t

43

elgian ferent IMA,

s (see cohort

roach elgian ls are ished

mainly

ion to on at

ata as aking scribe

o the

44

3.1. Data soBelgian life tabOverall survivabe.STAT (http:/Belgian CanceThe Belgian Ccollects data cstatistics from tBelgian organAs recommendorganized screeprogram are woprograms ahttp://www.brumdépistage desFrançaise) andhttp://www.zorgIntermutualistiThe Intermutuasickness fundsnational screendefined by theinformation on focus on the tconfirmation anDutch Nation(DNETB)85. The Dutch Npublished a recontaining inforpopulation.

ources ble (2009) al was taken fro//statbel.fgov.be) er Registry (BCRCancer Registry Fconcerning new chese data (http://wized screening

ded by Europeanening programmeomen aged 50 to are organizedmammo.be/), Cens cancers (CCRd BorstKankerOpg-en-gezondheid.bic Agency (IMA)

alistic Agency (IMAs. IMA compiledning program cone program (50-6

persons outsidetests used, delaynd treatments follonal Evaluation

ational Evaluatioeport with their rmation on age s

om the Belgian

R) Foundation is ancancer cases in www.kankerregist

Commission, Bee. The target age 69 years. Belgiand by: Br

ntre CommunautaRef: http://www.cpsporing (BKO) (be/).

A) centralises dat and published

ntaining data on t69 years). IMA e the target ageys between screeowing testing (http

Team for Bre

on Team for Bfindings covering

specific stage dist

S

life table of 200

n public institutioBelgium and ma

ter.org/).

elgium started a groups as define

n breast cancer scrumammo (Baire de Référenceccref.org/) (Comm(Vlaamse Gemee

a coming from allseveral reports

the target age grcomplemented t-group, with a pening tests and p://www.nic-ima.beeast cancer sc

Breast cancer scg the period 19tributions in the s

Screening Breast C

09 from

n which akes up

national d by the creening ruxelles,

e pour le munauté enschap:

Belgian on the

roups as his with

particular possible e/).

creening

creening 90-2007

screened

STNin(lointh

3InmfrB7folelisaaacTdtiT•

Cancer

SEER database The Surveillance, National Cancer Inn an effort to redhttp://seer.cancerocations and sourn 1973. As they hese in the mode

3.2. Model den a first simple amortality caused brom the results oBelgian life table.74 is similar to tollowing Barratt eevel over first fivenearly to nothing

saved can then band effects on quaand stage-shift is approach was onlcomplex approachThe second apprdata on incidenceime dependent stThe model compa A cohort of w

the populationparticipates inby screening,screening. Thcases (intervaThe screen dthan the canc

Epidemiology, annstitute works to duce the burden r.gov/). SEER collrces throughout thused an outdatel.

escription approach we appby screening comof the meta-analWe assume herethe reduction in et al 200536 that e years after startg over five yearse derived from thality of life resultinmore difficult to a

ly used for cross h that makes use oroach makes usee of invasive cancate transition cohres 2 cohorts:

women starting at n in the age gron the screening an, depending on p

here is a mix of scal cancers and cdetected cancers ers not detected b

nd End Results (Sprovide informatioof cancer amon

lects data on canche United States.d distribution we

plied the 22% reduming from RCT alysis of Gøtzschee that the reductio

other age groupbenefit accrues

ting screening ans after stopping he life table. Howng from earlier diaassess in this apvalidation by com

of the stage-shift e of the Belgian Ccer and DCIS forort model with an

age 70 where scup 70-74, where nd where a part oparticipation rate creen detected ancancers amongstwill have a diffe

by screening.

KCE Report

SEER) Program oon on cancer statg the U.S. Popucer cases from va Data collection bcould not incorp

uction in breast cand its range, rese et al, 20084 oon in women ageps. We also asslinearly to a mad that benefit decscreening. Life

wever, effects of hagnosis, over-diagpproach. Thereforemparing it with a caused by screen

Cancer Registry (r the constructionnual cycles.

reening is extenda part of the wo

of the cancers is fand sensitivity o

nd not screen dett unscreend womerent stage distrib

t 176

of the tistics lation

arious began porate

ancer sulting n the

ed 70-sume, aximal clines years

harms gnosis e this more

ning. BCR)

n of a

ded to omen found of the ected

mens). bution

KCE Report 176

• A cohort o

extended bthe stage d

All women are number of QAcompared. OveWe assume tha• Survival an

the tumor women, an

• All benefit in stage-dis

Harm caused accounted for sinterval in theproportion womthe screening roFigure 3.1 showtransitions betwIn the unscreenyear are determ• Incidence o• Stage distr• Stage spec• Age specifOn top of that, fdetermined by s• Lead time a• The propo

found by sc

6

of women startinbeyond the age ofdistribution of the followed to deathLYs and deaths

erall mortality is noat: nd quality of life oat the moment t

nd not on the presof the screening rstribution caused by false positiv

separately, by asse participation wmen that are alive ound actually takews the different c

ween them. ned cohort, transi

mined by: of breast cancer; ribution of unscreecific survival; and ic overall mortalityfor the cohort whesome aspects of tas part of the can

ortion of cancers creening and thei

g at age 70 whef 69 years. For thnon screened.

h. The cumulativeto breast cance

ot compared as in

f the women depethe tumor is detesence or absence results from the sby the screening.

ves at the momesuming 3 screeniomen and applyand without brea

es place. compartments in

itions between co

ened cancers;

y due to other cauere screening takethe screening: cers will be foundfound by scree

r respective stage

S

ere the screeninhis cohort all wom

number of life yer of the two coh

n the end everybod

ends only on the ected and the agof screening; tage-shift, the diff. ent of the screeng rounds with a ying recall ratesast cancer at the

the two cohorts

ompartments from

uses. es place, transitio

d earlier; ening and propore distributions.

Screening Breast C

g is not men have

ears, the horts are dy dies.

stage of e of the

ferences

ening is 2 years

s at the moment

and the

m year to

n is also

rtion not

AddsymTmea

Cancer

As survival and diagnosis in the mdiagnosis and stscreening is applieyears (or 3 in senmanageable. Transitions betweemoment the diagnevolves after treaanymore.

quality of life dmodel, a separateage, and stage ed during 5 years nsitivity analysis)

en stages are notnosis is made follatment it does no

epends on both e compartment is

specific survivaland there is an athe number of co

t included as stagelowed by treatme

ot necessarily go

age and time made for each a

l is than appliedassumed lead timeompartments rem

es are assessed aent. Even if the ca

through the 4 s

45

since age of d. As e of 2 ained

at the ancer tages

46

Figure 3.1: Co

Cohorscree

Cow

scre

mparison of the

Healthy  women

Healthy  women

rt with ening

ohortwithout eening

two cohorts with

Id

is

S

h and without a s

Invasive cancer detected by screeni

DCIS

interval cancer in screened women

Invasive cancer in unscreened wome

Invasive cancer in unscreened wome

DCIS

Screening Breast C

screening progra

IIIIIIIV

IIIIIIIV

IIIIIIIV

IIIIIIIV

ing

en

en

Cancer

am

All c

All c

cause deaths

cause deaths

KCE Reportt 176

KCE Report 176

Figure 3.2: Co

6

mpartments in th

Healthy women

he two cohorts a

d

S

and the transition

Breastcancer stage I 

Breastcancer stage IV

Breastcancer stage II

Breastcancer stage III

DCIS &over‐

diagnosed 

Screening Breast C

ns between them

Death

Cancer

m

47

48

3.3. Descrip3.3.1. Age sOverall survivabe.STAT (http:/mortality based3.3.2. BreasFor the baselinethe 4 stages fowere used. Thethe IMA data wmammography 172 on breastassume that anpurposes, so ware less contamFor the situatiogroup will increa• Lead time

because onumber of this shift dused 2 yeaanalysis.

• Over diagbased on review abodiagnosis e

• Over diagdifferent wDCIS per 1place comlimited amcontrast widrop in DC

ption of the parspecific overall sal was taken fro//statbel.fgov.be) on data from thest cancer incidene without screeninr invasive for the

ere is some opporwe infer that in in the past 2 yea

t cancer screenin important part owe choose to useminated by opportuon where screenase with a numbe, cancers that wo

of lead time. This cases in the foll

depends on the aars lead time in t

gnosis invasive the findings in th

ove under 2.1.3.5.excluding DCIS.

gnosis DCIS, weway: we use the o100 000 is twice

mpared to the agemount of opportu

th the Brussels caCIS is much less p

rameters urvival

om the Belgian after adjusting fo Belgian Cancer rnce ng the BCR data oage group 70-74

rtunistic screeningFlanders the covars is 18% (for deng in risk group

of this is also for de data issued fromunistic screening.ning takes place,er of cancers comuld have appearewill lead to a co

lowing years. Theassumed lead timthe baseline and

cancer, we modhe literature as d. We assume a ra

e model the overobservation that iin the group 60-6e-groups 70-74 anistic screening apital region and Wronounced. So we

S

life table of 200or breast cancer register.

on incidence of D4 of the period 20g in that age grouverage with at leetails see the KCps)2. Given that diagnostic and fom Flanders becau , incidence in thing from two sour

ed later but are fouompensatory dece moment and deme (see point 3.2

3 years in the se

deled the over ddescribed in the lange of 2 to 30%

r diagnosis of DCn Flanders the in

69 where screeninand 75-79 wheretakes place. Th

Walloon region we take as an estim

Screening Breast C

09 from specific

DCIS and 04-2008

up. From east one

CE report we can llows up use they

e 70-74 rces: und now rease in egree of 2.2). We ensitivity

iagnosis iterature for over

CIS in a ncidence ng takes e only a his is in

where the mation of

3W3T6c7Ws3WsbsthmApaTthp

Cancer

over diagnosithe age-groupfact that screeDCIS. This brwomen per ye

3.3.3. ParticipaWe used a 70% pa3.3.4. ProportioThe data of the Be69, 49% of the cascancer or not part75% of the found We used a proporscreening of 70%3.3.5. Recall raWe assume a recscreening programbe an extension sensitivity analysishe more pessimmoment in certain As a baseline we plausible range foand adding 20%). The short term imhe percentage chpositive results.

s the difference ips 60-69 and 70-ening coverage isrings us to an oveear. ation rate articipation (plauson of screen detelgian screening pses are found by ticipating in the sccancers are screertion of cancers fo(plausible range 6ate call rate of 3.5%m concerning folloof the screening

s we used 2% in aistic scenario (1regions). assume a delay

or the sensitivity a

mpact of positive rhange in utility va

in DCIS incidence-74, augmented b only 60% as a prer diagnosis of DC

sible range 60% totected breast caprogram show thascreening, and thcreening. Among en-detected and 2ound among the w60% to 80%).

% based on the dow up rounds (as

g among women an optimistic scen0% recall rates

of 45 days, baseanalysis of 36 and

results at screenialues between tr

KCE Report

e in Flanders betby 1.5 to adjust foroxy for overdiagnCIS of 40 per 100

o 80%) as baselinancers at in the age grouhe rest is either in

the screened wo25% is interval cawomen participat

data from the Fles the screening waged 50-69. Fo

nario and 5 and 10are observed fo

ed on IMA data, wd 45 days (subtra

ing were measurerue negative and

t 176

tween or the nosed 0 000

ne.

up 50-terval

omen, ancer. ing in

emish would or the 0% in

or the

with a acting

ed by false

KCE Report 176

3.3.6. StageWe take estimascreened and uprovided by theFor the stage dstage distributioyears 2004 - underestimatedgoing on, see aFor stage distriis based on thecancer screeninfor the age gdistributions frostage shift we tnot have date stage distributiobe the same, baThe Flemish sscreen detecteparticipants, coperiod 2001-20non participants

6

e distribution andations of the stagunscreened from

e Flemish screenindistribution in the on amongst wom2008 a good es

d as there is somabove. bution in the scree data from the Dng report of 2009group 70-74 froom different sourthink this approximon screen detecton of cases amonased on the data screening prograed cancers, interollected amongst06. Stage distribus is very similar.

d stage shift ge distribution fothe BCR data o

ng program. unscreened wom

men in the group 7stimation. The stme opportunistic

eened population, Dutch National Ev9 (DNETB)85 whom 1998-2007. Arces is a suboptmates best the Beted cancer in thisng the non screenfrom the Flemish m provided datarval cancers andt women who gaution of interval ca

S

r breast cancer aon the Flanders a

men, we can cons70-74 in Flandersage shift will bescreening in tha

the base case esvaluation Team foo provide data speAlthough using 2timal way of modelgian situation, as age group. We ned and interval cscreening progra

a on the stagesd cancers amonave their consenancers and cance

Screening Breast C

amongst and data

sider the s for the

e slightly at group

stimation or Breast ecifically 2 stage deling a

as we do assume

cancer to m. among gst non

nt in the r among

TinF

S

I

II

II

IV

T

T

ScsBp2S

Cancer

Table 3.1: Stage nterval cancers Flemish screenin

Screencancer

Stage n

2586

I 1306

II 232

V 15

TOTAL 4139

This baseline stag

Stage distributioncancers not founscreening BCR data (Flemispopulation,70-74y2008) Stage  %

I  31.6II  42.3III  16.6IV  9.5

distribution amoand cancers a

ng program 2001

n detected rs

In

% n

62.5% 62

31.6% 65

5.6% 20

0.4% 24

100% 15

ge shift we call Sce

n of nd by

sh y, 2004-

% 

6%  

3% 6% 5% 

ong screen deteamong non part-2006.

nterval cancers

%

24 41.5%

56 43.6%

00 13.3%

4 1.6%

504 100%

enario 1:

StacanscrDascrSt

ected breast canticipants, age 5

Cancers amonon participan

n %

1454 41.8%

1460 42.0%

493 14.2%

71 2.0%

3478 100%

age distribution oncers found by reening

ata of the DNETBreening report 20tage  % 

I  80%II  18.7III  0.8%IV  0.5%

49

ncers, 50-69,

ngst nts

%

%

%

%

%

of

B 009

% % % % 

50

Important remscreen detectecancers and nfound by screeother parameteFor the sensitivAs the stage dBreast cancer scan be achievethe stage-distribfrom the FlemisThis we call Sce

Stage distributcancers not foscreening BCR data (Flempopulation,70-2004-2008) Stage 

I  3II  4III  1IV 

In a third scenaInstead of usinwomen, we assthe stage distribthe stage distrifor Flanders fro

mark: It is imported cancers and

nonparticipants kening. In most cas

er values of the scvity analysis we usdistribution from screening report od in the Belgian cbution for screen sh cancer screeninenario 2:

tion of ound by

mish -74 years,

% 

31.6%  

42.3% 16.6% 9.5% 

ario we use a slighng stage distributsume that introdubution amongst albution of the wom

om the Belgian bre

tant to note that that in the coho

eep the stage dses this is around creening and variese 2 supplementathe Dutch Natioof 2009 may be mcontext, we used a

detected patientsng program.

htly different modetions amongst sccing screening in ll breast cancer cmen 60-69 in the east cancer regist

S

this shift concerrt with screeningistribution of can50% but depend

es in time. ry scenario’s: nal Evaluation Tmore favorable thas an alternative ss of the age grou

Stage distribucancers foundscreening (Flescreening pro(50-69 years)Stage

I  62II  31III  5IV  0

eling approach. creened and unsthe group 69-74

cases in the popusame period, us

try.

Screening Breast C

rns only interval ncer not s on the

Team for han what scenario up 50-69

ution of d by emish ogramme

% 

2.5% 1.6% 5.6% 0.4% 

screened will shift

ulation to ing data

T

ScsBp2S

3Ssywasw•

•

Cancer

This we call scena

Stage distributioncancers not founscreening BCR data (Flemispopulation,70-742004-2008) Stage  %

I  31.6II  42.3III  16.6IV  9.5%

3.3.7. Stage spStage specific susurvival data (takeyears. We used website (http://wwappendix 4.1). Wescreened and unswe used also: Entirely the

stagegroup. Tfor women areflect the facwell but it is aMoreover, theyears ago, thi

British surviv(http://info.canbut survival isof the problemsurvival of pevolution in br

ario 3

n of nd by

sh years,

6%  

3% 6% % 

pecific relative survival was takenen from KCE repodata from the D

ww.cijfersoverkanke assumed that sscreened breast c

Dutch survival dThe relative survivbove 70 compar

ct that older womealso possible thate data include pas may also explaival data comingncerresearchuk.ors considerably lowms with 10 year ersons treated areast cancer treat

StaamcanlevlevFlaSta

IIIIIV

urvival n from Belgian ort 150A)86. We oDutch cancer regker.nl) to supplemurvival conditiona

cancer patients. A

data for women val curve shows aed with the overen support the invt there is undertreatients that were in the lower relativg from breast rg/) They provide

wer than the Dutchsurvival data is t

at least 11 yearstment this is a lon

KCE Report

age distribution mongst all breast

ncers if screeninvels are similar tovels among 60-69anders age % 

I  45.7% I  35.9% II  12.5% V  5.9% 

stage specific aonly have data upgister taken from

ment until 7 yearsal on stage is simAs a sensitivity ana

above 70 yearsa lower relative surall survival. Thisvasive treatmentseatment of the eltreated more tha

ve survival. cancer research10 years surviva

h or Belgian datathe fact that it res ago, given theg time.

t 176

ng o 9 in

nnual p to 5 m the s (see ilar in alysis

s per urvival s may s less derly. an 20

h UK l data . One

eflects e fast

KCE Report 176

• Belgian su

coming frotreatment a

We did not useso that survivaland difficult to iThe survival cu3.3.8. QALYNumber of life was adjusted fo(see point 2.3).We made some• Utility value

age but penot vary acthis). For increase.

• Patients wpopulation.

• In the asseresults, moby screenin

6

urvival data supplom87. The problapply here as for te US SEER data l curves per stagencorporate in the rves can be found

Y years was calculor the quality of l

e assumptions: es at start of the mrcentage changesccording to the agthe sensitivity a

with negative resu. essment of utility obility and ability ong.

emented by Frenlem of the evothe British data. as they use an o

e are not comparmodel.

d in the annex.

lated for each stalife (QALYs), bas

model (before scrs relative to thesege of the women analysis, we app

lts had utility val

values for true neof self-care were a

S

nch 10 year surviolution in breast

outdated staging rable to the other

age and a stage sed on a literature

reening) were strae values were ass(we did not have

ply a 20% redu

ues equal to the

egative and false assumed to be un

Screening Breast C

val data cancer

method, sources

and this e search

atified by sumed to

data on ction or

general

positive naffected

•

•

•

P

Cancer

In the study oonly two grouTherefore papatients) weresupported by same for patquality indicatchange this ptreated by coassumption aimpact of pcorresponding

Utility values fmetastatic paFor non-metastudy showinNevertheless,QALYs for tak

At baseline, wdiscount rates

Parameters used i

of Lidgren et al.80, ps, i.e. the first ye

atients in stage e assumed to hathe fact that for yients in stage I, tors in breast canicture because monservative surge

are not available partial versus tog to our inclusion for non-metastatic

atients were assuastatic patients, thng no significant , as a sensitivity king into account awe did not discous of 1.5%, 3% andin the model are s

non-metastatic pear of diagnosis aI, II, III (groupeve the same utili

years 2001-2006, II, III according

ncer86. Note that any cancer foundery. Neverthelessand we found nootal mastectomycriteria. c patients (after thumed to remain chis assumption isdifferences at y

analysis we applya variation of utilitunt QALYs. For thd 5% were appliedshown in table 3.2

patients were dividand the following yed as non metaty. This assumptthe treatment wato the KCE repomore recent data

d by screening ares, data to proveo study compariny on quality of

he year of surgeryconstant across ys supported by ayear 5, 10, and y a 20% decremety values across yhe sensitivity anad. 2.

51

ded in years. astatic ion is

as the ort on a may e now e this g the f life

y) and years. n US 1581.

ent in years. alysis,

52

Table 3.2: Para

Parame

3.3.1 Age spe

3.3.2 Breast c

Lead tim Over-dia

cancer Over-dia

3.3.3 Participa3.3.4 Proporti

detected3.3.5 Recall r

Durationpositive

QALYs

3.3.6 Stage d

Stage I Stage II

ameters used in

eters

ecific overall surviv

cancer incidence

me agnosis invasive

agnosis DCIS

ation rate ion of screened d cancers ate

n of period after result lost in this period

istribution

the model

No screenin

val Belgian life-

BCR data (Flanders population, 2008)

BCR data (Fpopulation, 74years, 202008)

31.6% 42.3%

S

ng Base c

table Belgian

2004-

BCR dpopulaincreasover-diinvasivDCIS 2 years10.0%

40/100year 70.0%70.0%

3.5% (screen45 day

16.0%

Flemish 70-04-

Data oscreen

80.0%18.7%

Screening Breast C

case

n life-table

ata (Flemish ation, 2004-2008) sed by lead time.iagnosis ve cancer of

s

0 000 women per

Flemish ning program) ys

f the DNETB ning report 2009

Cancer

Sensitivity ana

Belgian life-tabl

BCR data (Flemincreased by leacancer of DCIS

3 years range from 3 to

40/100 000 wom

range from 60%range from 60%

range from 2%

range from 36 t

estimated betw

Scenario 2 Stage distributioFlemish screenprogramme (50

62.5% 31.6%

alysis

le

mish population, 2ad time. over-diag

30%

men per year

% to 80% % to 80%

to 10%

to 54 days

een 13% to 19%

Sceon of ing

0-69)

StagBCR60-6not

45.735.9

2004-2008) gnosis invasive

nario 3 ge distribution of R (Flemish women69 (screened and screened)

7% 9%

KCE Report

n

t 176

KCE Report 176

Stage I Stage IV

3.3.7 Stage s

survival

3.3.8 QALY Stage II

Stage II

Stage IV

Age rela

Discoun

6

II V

pecific relative

III IV

I IV

V

ated QALY

nted QALY

16.6% 9.5%

Belgian stagspecific annsurvival datasupplement7 years by Ddata -constant

-constant

-constant

-constant

S

0.8% 0.5%

ge nual a ed until Dutch

Belgianannualsuppleyears b

- const

-consta

-consta

-consta

Screening Breast C

n stage specific l survival data mented until 7 by Dutch data

tant

ant

ant

ant

Cancer

5.6% 0.4%

Dutch survival osurvival

-20.0% -20.0% -20.0% range from + 20 discounting rate

12.55.9%

or British survival

0% to -20%

e + 1.5%. 3% and

5% %

or Belgian/French

5%

h

53

54

3.4. ResultsIn the baseline of life saved pe395 per 100 00deaths would bbeing a reductioBecause of themodel structureis not due to rasource of inforsensitivity anaprobability-distrTable 3.4 showused for this anand justificationThe number of assumptions. Tdifferent assumuncertain or vagained rather thapart from the vAssumed degreand under the QALY would bslightly, this duenew case in thebut the effect isRecall rates of Ten per cent reAssumptions onimpact on yeaBritish survival loss of QALYs French 10 year

s scenario the mod

er 100 000 (13,1 p00 (3.9 per 1000) be averted per 1on of 21% (numbee considerable une we did an extenandom error but drmation on the palysis, as it waributions in a mea

ws the results of thnalysis was discun of chosen valuesf years of life gainThe number of QAmptions. This is ariable parametehan on mortality, values accorded tee of over-diagno

higher assumedbe lost instead oe to the fact that e model, one couls very small.

10% also can shecall rates are actun the choice of thrs of life gained data increase thein certain scenari

r survival is somew

del predicts that thper 1000) women QALYs. The mod00 000 women ser needed to be oncertainty surrounnsive sensitivity adue to issues relaparameter. We das not possible ningful way.

he sensitivity analussed in 3.3, descs. ned remains fairlyALY gained or lost

partly due to thrs have an impasuch as high rec

to the QALYs. osis has a strong d values of 20%of gained. Years an over diagnosed argue that this i

hift the balance toually found in somhe appropriate sur

and QALYs gaie number of life yos. Belgian survivwhere in between

S

here would be 130invited for screen

del also predicts screened (1.3 pe

offered screening:nding the parametanalysis. Most uncating to the right cid not do a probto choose app

ysis, the plausiblecription of the par

y constant under t varies much mohe fact the a lotact on the qualitcall rates, over dia

impact on QALYsor 30% even imof life gained in

ed case cannot beis somewhat of an

owards a loss of me parts of Belgiumrvival curve have ned. The Dutch

years gained but lval data suppleme.

Screening Breast C

07 years ning and that 128

er 1000), 782). ters and certainty

choice of babilistic propriate

e ranges rameters

different re under t of the y of life agnosis,

s gained mply that ncreases ecome a n artifact

QALYs. m. both an and the ead to a ented by

InoTththQTndsIIegainAQAredp3Aredp1AGsy

Cancer

ncreasing the assof life gained and QThe model’s estimhe valuation of thhe decrease in qQALYs gained, asThe estimations conot vary much in decrement in quascenarios: (i) decrII and IV with 20effect of increasingains in QALYs duas persons in stagn contrast to the LAs could be expecQALYs gained. As a worst case secall rate at 10%

days and using thprogram (scenario307 QALYs per 10As a best case scecall rate at 2%,

days and using thprogram (scenario

626 QALYs per 1Applying the 22%Götzsche et al. tosimilar result, 139 years of life saved

sumed lead time tQALYs.

mation of the numbhese QALYs. Dimquality of life dues could be expecteoming from the Lfunction of the d

ality of life due toreasing stage II II0% or (iii) decreag the number of ue to the stage shge I have in this sLidgren data. cted, introducing d

scenario, we set th%, loss of QALYs he stage distributio 2). This gives a00 000. cenario, we set tloss of QALYs p

he stage distribuo 1). This gives a 100 000. % reduction in mo the Belgian life t

cancers deaths dd.

to 3 years has an

ber of QALYs gainminishing the age e to old age, deced. idgren’s paper areifferent stages. W

o increasing stageI and IV with 20%

asing stage IV wQALYs gained, bhift alone outside cenario a better a

discount rates de

he estimation of oper recall at 0.19ion coming from gain of 872 Yea

he estimation of per recall at 0.13 tion coming fromgain of 1704 Yea

mortality from thtable, as describedue to breast can

KCE Report

n impact on both

ned or lost depenrelated QALYs, t

creases the numb

e fairly uniform anWe introduced a le at diagnosis, w

%, (ii) decreasing ith 20%. This ha

because there arethe effect on mor

assumed quality o

creases the numb

over diagnosis at 9 during a period the Flemish scrers of Life but a lo

over-diagnosis aduring a period

m the Dutch scrers of Life and a g

e meta-analysis ed above, gives ancer avoided and

t 176

years

ds on this is ber of

nd do larger with 3 stage

as the e also rtality, of life,

ber of

20%, of 54 ening

oss of

t 3%, of 36 ening ain of

from a very

1145

KCE Report 176

Table 3.3 Mode

Scenario

Baseline

Worst case

Best case

6

eling results: bas

Assump

Over recall loss of Qduring astage Dutch (scenarioOver recall loss of Qduring astage Flemish (scenarioOver recall loss of Qduring astage Dutch (scenario

seline, worst and

ptions

diagnosis: rate at 3

QALYs per recall a period of 45 distribution comscreening prog

o 1) diagnosis: rate at

QALYs per recall a period of 54 distribution comscreening prog

o 2) diagnosis: rate at

QALYs per recall a period of 36 distribution comscreening prog

o 1)

S

d best case scen

Years of lPer 100 00women

10%3.5%0.16days ming gram

1307 gaine

20%10%0.19 days ming gram

872 gained

3%2%

0.13 days ming gram

1704 gaine

Screening Breast C

nario.

ife 00

Quality adPer 100 00women

ed 395 gained

d 307 lost

ed 1626 gaine

Cancer

djusted years of l00

d

ed

life

55

56

Table 3.4 Mode

Baseline Assumed over0.03 0.05 0.1 0.2 0.3 Recall rate 0.02 0.035 0.05 0.1 Period betweeduration 36 days 45 days 54 days Period betweeQALYs lost QALYs loss peQALYs loss peQALYs loss peParticipation r0.6

eling results: sen

rdiagnosis

en false positive

en false positive

eriod 13% eriod 16% er period 19% rate

nsitivity analysis

e and confirmat

and confirmatio

S

s.

Stagescena

Years1307 13041305130713101314 1307130713071307

ion test:

130713071307

on test:%

130713071307 1120

Screening Breast C

eshift ario 1

s of life QALYs395 526 489 395 208 22 442 395 348 190

417 395 373

416 395 374 281

Cancer

Stageshift scenario 2

Years of life1014 1011 1012 1014 1018 1022 1014 1014 1014 1014

1014 1014 1014

1014 1014 1014 869

Stsc

QALYs Ye186 12 317 12280 12186 120 12-187 12 234 12186 12139 12-19 12

208 12186 12164 12

207 12186 12166 12 102 na

tageshift cenario 3

ears of life QA246 420

245 551245 514246 420249 232251 45

246 459246 420246 380246 249

246 438246 420246 401

246 449246 434246 420

a na

KCE Report

ALYs 0

1 4 0 2

9 0 0 9

8 0 1

9 4 0

t 176

KCE Report 176

0.7 0.8 Effectiveness 0.6 0.7 0.8 Survival curveDutch survivalBritisch survivBelgian survivAssumed leadAll QALYs minAll QALYs plusStage II III IV -2Stage III IV -20Stage IV -20 Discounted QADiscount rate Discount rate 3Discount rate 5

6

screening amon

e by stage from ol val val supplementedd time 3 years nus 20% s 20% 20 0

ALYs 1.5% for QALYs 3% for QALYs 5% for QALYs

ngst participants

other sources

d by French data

S

13071493 112013071493 16071714

a 1460109813071307130713071307 130713071307

Screening Breast C

395 509 281 395 509 710 399 473 118 -948 1587 903 648 450 297 215 138

Cancer

1014 1159 869 1014 1159 1181 1148 1045 875 1014 1014 1014 1014 1014 1014 1014 1014

186 na270 na 102 na186 na270 na 310 14-3 1596 1377 11-1089 121310 12465 12370 12241 12 121 1267 1215 12

a naa na

a naa naa na

481 505585 374365 477169 187246 -78246 153246 na246 na246 na

246 274246 193246 114

5 4 7 7 7

34

4 3 4

57

58

3.5. DiscusUnder baselinelimited impact osaved, amountiin that period andays of life gainThis results fallfound as reportranged from 9 tthat completelyYears of life gachoose a worstfrom 872 to 170on the meta-anthat this estimaestimation methgained are fairlyThe gain in quonly 3.9 QALYwomen) offereddata in anothescreening for 5shows that undin this age groimportant of thcertain parts of addressed befoThe worst casescreened, we mare still reasonelements wereeffect is sometquality of life pQALYs gained This is due to false positives a

sion e assumptions, son breast cancer ding to 1.4 death and 13 years of lifened per women ofl within the rangeted by Mandelblatto 22 per thousan

y different data andained remained fat and best case s04. It correspondsalysis of Götzsch

ation comes from hod. This indicatey robust and consality adjusted life

Ys per 1000 womd screening and uer way by statin5 years to gain

der certain assumoup would actualese is an assum

f Belgium, so thesore proceeding. e scenario would made sure that thnable assumption not considered imes mixed. Brin

per age-group incdepending on ththe fact that intr

and over diagnosi

screening in the deaths avoided a

avoided per 1000 e saved per 1000 ffered screening. e that the modelett et al in 200948, wnd women screend model structureirly constant in thscenario, with yeas also with the sime et al.4 and the Ba completely diff

es that the estimasistent with other s years (QALYs) i

men (1.4 quality ncertainty is large

ng that 250 womone year of life.ptions introducinglly generate a lo

med recall rate ofse high recall rate

imply a loss of 3 e assumptions of

ns and not undulin the worst casging down the bacreases or decreae chosen values

roducing screeninis but gains due to

S

age group 70-74nd number of yeawomen offered scwomen, amountin

ers of the CISNETwhere years of lifened. This, despites were used. e sensitivity analyars of life gained mplified estimatioBelgian life tables,ferent source of dations of the yeastudies. is considerably leadjusted day of

er. One can presemen need to be The sensitivity

g breast cancer scoss of QALYs. Thf 10%, as is the

es should certainly

QALYs per 1000f this worst case sy extreme. A nuse scenario becaaseline estimationases the final nuof the other para

ng induces losseso the stage shift.

Screening Breast C

4 has a ars of life creening ng to 4.7

T project e gained the fact

ysis. We ranging

on based , despite data and rs of life

ess, with life per

ent these offered

analysis creening he most case in

y first be

0 women scenario

umber of ause the n for the umber of ameters. s due to

UsTyupocuuccatooisCZlin51freTitcbandoTsina

Cancer

Under the best cascreened. The higher variabyears of life losuncertainty arounparticular concernother hand rather countries and in uncertainty arounduncertainty concecancer states but cost-effectivenessaddressed if we wo stage IV has onor lost as survival s low. Carles et al. 201Zeelen, found an fe years gained p

not report the QA50-69, as it was

.86 QALYs per 1rom 45-69. Intereet al, 201158 into thThe model takes it does not take cancers would habecause screeninare not life threatenon screen detectdetected cases is of stage, and thatThis indicates thaselection of less anterval cancers hattending screenin

ase scenario one w

bility seen in the t has a numbed key parameter

ning over-diagnosreflects real undBelgium betwee

d the valuation oferning the qualitalso age specific analyses are

want to have meanly a limited impain this stage is s

138, in an adaptincremental bene

per 1000 women cALYs gained with

dominated by sc1 000 were gaineestingly, they did nheir calculations, nto account over-into account leng

ave a slower cling tends to pick-uening. Follow up sted cancer in thebetter than case

t survival of intervat there may indaggressive cancehave a better sung indicates that

would gain 16 QA

estimation of theer of reasons. Trs that determineis. Variability due

derlying differencen regions. Theref the quality of lify of life surrounquality of life in Bconsidered, this

aningful results. Qct on overall numhort and proportio

ation of the CISefit for biannual sccompared to a schextending the screening from 45-

ed by extending tnot incorporate thbut used US surv-diagnosis and leagth bias, the factical course and

up slow growing tstudies of screen

e literature show tes among non parval cases is somdeed be a lengtrs by screening.

urvival than canceother factors also

KCE Report

ALYs per 1000 wo

e QALYs comparThere is considee a loss of QALYe to recall rates oes in practice bete is also considefe, and this is notnding different bBelgium. If in the fs problem shoulQuality of life attribmbers of QALYs g

on of stage IV pa

NET model of Lcreening 50-74 ofhedule 50-69. Thecreening to 50-74- 69, but reportedthe screening to 4he results of Vilapvival data. ad time bias. Howt that screen-dethave a better sutumors some of wdetected cancers

that survival of scrticipants, indepenewhat in betweenth time bias, thrHowever, the facer among womeo play a role, suc

t 176

omen

red to erable Ys, in on the tween erable t only breast future d be buted ained

atients

Lee & f 2.78 ey did from

d that 45-74 prinyo

wever, ected

urvival which s and creen ndent n88-91. rough ct that n not ch as

KCE Report 176

selection bias amongst womeadjustment for sand on effectinecessarily negthreatening canimpact on efficand greater cosWe unfortunateunscreened woMoreover, therecurves that will survival may beAnother majordistributions of on stage distrcancers and thscreening are vWe choose a mshift and its coessentially tumoto stay closer incorporating pathat the model overall effect odetected basedcan only evaluaBelgium, we cahowever needeto use the samewe would just mIn conclusion, tchoice of the pthe results. ThYears of Life gthere is eviden

6

(such as the soen non attending stage. However leveness, as detegatively correlatencers at an earlierciency, as detectist for no benefit toely did not have domen, tumors foe is in general coapply in the futur

e outdated. r source of uncthe diagnosed c

ibution show thae cancer amongs

very similar. modeling approac

onsequences, in cor growth modelsto the data and arameters based is less flexible an

of screening on td on Belgian dataate the effect of thannot vary the sced to parameterizee parameters that

merely replicate ththere is considera

parameters, so a is uncertainty is

gained and QALYce that continuing

ocial class or othscreening) and reength time has no

ection of slow gre with the ability r stage. Length timon of indolent tu

o women. ata on stage spec

ound by screeninonsiderable uncerte, as treatment ev

certainty is the cancers and stageat the stage distst the people who

ch that is essentcontrast to most s. This has the adv

make less use on Belgian data, nd has more simpthe proportion of a in the group 50he screening schereening interval. We the CISNET mot are already usedhem. able structural unlot of caution is nreflected in the

Ys gained in the eg screening until

S

er health relatedesidual confoundo direct impact onrowing tumors dto detect potenti

me has indeed a numors means mo

cific survival for tung and interval ctainty around thevolves and actual

right choice oe-shift. The Flemtributions of the o do not participat

tially based on thCISNET models vantage that it alloof unobserved vabut has the disadplifications. We mcancers that are-69. This implies

edules actually in We do not have

odels and would bd in the published

certainty around needed when intewide range of esend result. Neverthe age of 74 ye

Screening Breast C

d factors ing after efficacy oes not ially life-negative

ore harm

umors in cancers. survival data on

of stage ish data interval

te in the

he stage that are owed us ariables,

dvantage model an e screen

that we place in the data

be forced models,

the right erpreting stimated rtheless, ears has

muthloa

Cancer

modest effect on tuncertainty on thehat under reasonoss of quality adjuacceptable level b

the number of Lifee effect on qualitynable assumptionusted life years. Itefore extending s

e Years Saved buy adjusted life yeas the interventiont is important to b

screening.

ut there is considears, and the data n may even leadbring the recall rat

59

erable show

d to a tes to

60

4. ANSWWhat are clinbreast canceryears?

4.1. Breast What is the effescreening on thfor breast cancobtain an extra predicts that 12(1.3 per 1000),

4.2. Delay bHow long is thcancer relatedbetween 4 and

4.3. OveralWhat is the effescreening on tyears) of breasunclear. Studiemortality reduct

4.4. MorbidWhat is the effescreening on min randomized cor reject the hycancer diseasemorbidity may bcurrently at ourthe most recentconservative sadvanced stage

WER TO CLnical benefits anr organized scre

cancer relatedect of an extensiohe breast cancer rcer between the 13 years of life fo

28 deaths would being a reduction

between the sce delay between

d mortality reduc7 years after scre

l mortality ect of an extensiothe overall mortast cancer organizes did not have tion.

ity ect of an extensio

morbidity? We foucontrol trials. In o

ypothesis that scre. Aim of screeninbe diminish by lesr disposal do not t data (KCE repor

surgery versus 3es (C Stage I an

LINICAL QUnd specific harmeening in wome

d mortality n (70-74 years) orelated mortality?ages of 70 and

or 1,000 women sbe averted per 1

n of 21%.

creening and th the screening action? The morteening

n (70-74 years) oality? The effect zed screening onstatistical power

n (70-74 years) ond no data relatether words, on theening reduces thg is to detect minss aggressive treenable us to ratifrt 150)86 show 58%38% of total mand II). Nearly 90%

S

UESTIONSms of an extenen between 70

f breast cancer orThe continued sc74 makes it pos

screened. The mo00 000 women s

he mortality rednd the associatedtality reduction

f breast cancer orof an extension

n the overall mor to detect an a

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h related Life Res.

A. Health or breast

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685-99. Health-

hort-term y of Life

van 90-2007.

S, Van er. Good owledge 273/101)

8

8

8

9

9

9

9

9

9

Cancer

Available http://kce.f

87. INC. Survétat des lie

88. Mook S, Vvan Leeuwdetection 2011;103(

89. Cortesi L, Prognosispopulation

90. Joensuu HT, Kataja detected 2004;292(

91. Olsson A,J. Tumourby screen

92. PhysiciansPreventive

93. Woloshin mammogr2010;303(

94. Jorgensenfunded sc

95. Perry N, BL. Europescreening Oncol. 200

fgov.be/index_envie attendue des peux. 2010.

Van 't Veer LJ, Ruwen FE, et al. In

in invasive br(7):585-97. Chiuri VE, Rusce

s of screen-deten based study. BMH, Lehtimaki T, Ho

V, et al. Risk foby mammograph(9):1064-73. Borgquist S, Butr-related factors aing. Br J Surg. 20s AAoF. Summae Services. In: AA

S, Schwartz raphy screening: (2):164-5. n KJ, Gotzsche reening mammog

Broeders M, de Wean guidelines fo

and diagnosis. F08;19(4):614-22.

.aspx?SGREF=52patients atteints d

utgers EJ, Ravdin ndependent prognreast cancer. J

elli S, Bellelli V, Nected breast ca

MC Cancer. 2006;olli K, Elomaa L, Tor distant recurre

hy screening or o

tt S, Zackrisson Sand prognosis in b012;99(1):78-87. ary of Recomme

AFP Policy Action LM. The beneunderstanding t

PC. Content of graphy. BMJ. 2006

Wolf C, Tornberg Sor quality assuraFourth edition--sum

KCE Report

211&CREF=1884de cancers en Fra

PM, van de Veldenostic value of scJ Natl Cancer

Negri R, Rashid I, ancers: results 6:17. Turpeenniemi-Hujence of breast caother methods. J

S, Landberg G, Mbreast cancer det

endations for ClAAFP; 2010. efits and harmthe trade-offs. JA

invitations for pu6;332(7540):538-4, Holland R, von K

ance in breast cammary document

t 176

from: 47 ance :

e AO, creen

Inst.

et al. of a

janen ancer Jama.

Manjer ected

linical

ms of AMA.

ublicly 41. Karsa ancer t. Ann