Overdiagnosis in cancer

OVERDIAGNOSIS

IN

CANCER

• NASRULLA ABUTALEB..

Defining Overdiagnosis: A S/E of advances in Medicine

• Def:

• Irrelevan Dx.

• S/E: Harm from being a patient & from over Rx

• Only certain when ?

• Not false +ve

• Costly,, > $200 bn/ year US. BMJ

H. Gilbert Welch

Pathways to Overdiagnosis

• Screening ( pseudodisease)

• Redefining cut-off values:

• Using very sensitive tests (e.g. imaging) in

those with symptoms:

• Incidentally made “incidentalomas”

BMJ

Overdiagnosis in Medicine: examples

The original scope of this activity..

OVERDIAGNOSIS IN CANCER:

Outline:

• Introduction of overdx

• Screening bias

• Overdiagnosis in: Thyroid, Prostate, breast,

melanoma, lung, colon and cervical Ca..

- Incindentelomas

OVERDIAGNOSIS IN CANCER: HARD TO BELIEVE!

An example

• Neuroblastoma screening:

• e,g.

Urine screening offerred to 2,581,188 children at 1 yr

of age in 6 of 16 German states from 1995 to 2000. A

total of 2,117,600 in the remaining states served as

controls.

Incidence& Mortality:

N Engl J Med, Vol. 346, No. 14 April 4, 2002


Is it: To look for a cancer? Get screened!

V. strange: The

screened maintained

higher rates for both

early & late stages

SizeSpontaneous regression of

localized neuroblastoma

detected by mass screening.Journal of Clinical Oncology, 1998;

16(4):1265-1269

VMA levekcntrol

Surgery

Disease reservoir for three cancers:

Just look harder

J Natl Cancer Inst 2010;10:605–613

Early diagnosis always improve survival !

1. Lead time bias: so higher 5/10 yr

survival!

2. Overdiagnosis bias: so lower mortality

rates

H. Gilbert Welch

Cancer statistics!

JAMA, May 10, 2006—Vol 295, No. 18

How would ypu explain this phenomenon?

Rates of new diagnosis and death for five

types of cancer in the US, 1975-2005.

Adapted from Welch and Black12BMJ |2JUNE, 2012 |VOLUME 344

Epidemic of Dx not of cancers !

• Only a minority of the smallest tumors can be detected with the method

used !

• OPC can be regarded as a normal finding which should not be treated

when incidentally found.

• OPC < 5 mm in diameter to be called occult papillary tumor instead

Of carcinoma. Cancer 56531 -538, 1985.

Autopsy Series

Which is increasing? By which type? Why?

JAMA, May 10, 2006—Vol 295, No. 18

Straight & horizontal despite

Incidence

rates by

tumor size

(<1 cm, 2-2.9

cm, 3-3.9 cm,

and 4 cm),

1988 through

2005.

Cancer

August 15,

2009

Cancer

August

15, 2009

Straight & horizontal despite

a high resolution scale

Are we really saving

these patients with

thyroidectomies?

Or just harming?

Excellent disease-

specfic survival even

after 34 years follow

up: 1975 to 2009 (to

31/12/2009)

Mortality rate from all

thyroid Ca (PTC

accounted for 90.9%

in young and 87.2%

in older (<&>40) pt.:

0.4% among 14450 pt

4.7% among 20513 pt

Journal of Cancer Epidemiology, Volume 2012, Article ID 641372, 11 pages

Excellent results even for those

presented clinically! Why to search

for it!

<40

>40

J Natl Cancer Inst Monogr 2012;45:146–151


Large reservoir

Just biopsy more and more’’

12, 24,36 and you will find it

www.cancer.gov

N Engl J Med 2011;365:2013-9.

Rx improvement and awareness

more apparently than screening effect

• Lifetime risk of

prostate Ca :

16% (160K/yr),

med age 68

• Lifetime risk of

cancer death:

3% (29k/yr),

med age 80


Overdiagnosis in prostate screening : one death prevented to 20 or 50 or

to infinity number of men overdiagnosed

Mortality Results from a Randomized Prostate-

Cancer Screening Trial, PLCOnejm.org march 26, 2009

1993-2001 (Med 10 yrs): 76,693 (55-74) men, at 10 U.S centers,

randomized to annual screening (38,343, annual PSA X 6 years &

DRE for 4 years) or usual care (38,350).

At 7 year:

• More prostate Ca in the screened: 116/10,000 (2820 cancers) vs.

95/10,000 (2322 cancers) (R 1.22; 95% CI 1.16 to 1.29).

• The incidence of death: Less in the screened:1.7 vs 2.0/10,000

person yr (44 vs. 50 deaths) (R 1.13; 95% CI, 0.75 to 1.70).

• Conclusion: After 7 to 10 years of follow-up, the rate of death from

prostate cancer was very low and did not differ significantly between

the two study groups

PLCO

But Same!More!

Screening and Prostate-Cancer Mortality in a

Randomized European Study (ERSPC)nejm.org march 26, 2009

• 1991-2006 (Med 9 years, 7 countries), used PSA of 3 for biopsy

every 4 yrs, DRE 2X

• More cancers in the screened: 5990 vs. 4307

• Less Ca deaths in screened: 261 vs. 363 (20% lower, i.e or

0.0014/screened or 0.017 among the cancers)

• To prevent one death:

1410 men screened 48 men treated (with M& M)

ERSPC

Overdiagnosis

from PSA-

detected

cancer about

60% (34/58).

The 20%

reduction is Just

0.4% reduction,

NNS of 1400 &

NNT 48 are very

high

Screening for prostate cancer

Cochrane Prostatic Diseases and Urologic Cancers Group 31 JAN 2013

• Five RCTs on 341,342 participants, aged 45 to 80 years, using with

PSA +/- DRE with follow-up from 7 to 20 years. Our meta-analysis

indicated no statistically significant difference in prostate

cancer-specific mortality (risk ratio (RR) 1.00, CI 0.86 to 1.17). The

ERSPC was the only study that reported a significant reduction in

prostate cancer-specific mortality.

• A dx of prostate cancer was significantly greater in men

randomised to screening (RR 1.30, 95% CI 1.02 to 1.65). Localised

prostate cancer was more commonly diagnosed in men randomised

to screening (RR 1.79, 95% CI 1.19 to 2.70), whilst the advanced

cancer was significantly lower in the screening gp (RR 0.80, 95% CI

0.73 to 0.87). Obvious explanation! i.e not a benefit!

ACS Screening Recommendations

• Mene ≥ 50 with ≥ 10 year life expectancy should receive

information regarding possible benefits and limitations of

finding and treating prostate cancer early, and should be

offered both the PSA blood test and DRE annually

• Men in high risk groups (African Americans, men with close

family members---fathers, brothers, or sons---who have had

prostate cancer diagnosed at a young age): as above but

starting at age 45

Overdiagnosis/ harms:

Effect on mortalityFrom Dr. Srinivas Chakravarthy G.

Earlier Studies:

• HIP st. 62000 randomized to: combined annual mamogr.+

PE vs, unawareness 23% death reduction after 10 yrs F

up (only in >50); But c 1960’s,

• Edinburgh 1979:45000, also combined vs. none 17%

• 4 Swedish studies (incl Malmo st): 280000: 24%

• Canada 1 (50000, 40-49) and Canada 2 (40000,50-59):

combined annual mam+ PE vs. PE alone 0% in 13

then in 25 yrs FU ! (?DCIS)

Conclusion:

Annual mammography in women aged 40-59 does not reduce

mortality from breast cancer beyond that of physical examination or

usual care when adjuvant therapy for breast cancer is freely

available. Overall, 22% (106/484) of screen detected invasive breast

cancers were over-diagnosed

89 835 women, aged 40-59, randomly assigned to mammography (five annual

mammography) or control

All cause mortality

Breast cancer specific mortality

Breast cancer specific mortality from

cancers diagnosed in screening period

Conclusion: Annual

mammography (age 40-59)

does not reduce mortality from

breast cancer (22% :106/484

were over-diagnosed)

Interpretation:

Screening for breast

cancer with

mammography is

unjustified..

Lancet 2000; 355: 129–34

Effect on mortality

• Screening mammography

a doubling in early-

stage breast Ca from 112 to

234/100,000 women

(122/100,000).

• Late-stage Ca decreased

by 8%, from 102 to 94

(i.e.8/100,000) i.e only 8 of

the excess 122 expected to

progress to advanced Ca.

• Overdiagnosed in 1.3

million U.S. in past 30

years. In 2008: > 70,000

(31% of all breast cancers

diagnosed).

NEJM 367;21, november 22, 2012

?? screening effect on incidence

Screening Mammography & Incidence of Stage-Specific Breast Cancer in the United States, 1976–2008.

Bleyer A, Welch HG. N Engl J Med 2012;367:1998-2005

Basic

incidence is,

otherwise,

constant:

OverDx of early

cancer is not

limited to DCIS,

50% are localized

invasive cancer

Why we have

higher proportion

of advanced

breast cancer at

presentation?

NEJM 367;21 nejm.org 2002 november 22, 2012

er 22, 2012

Expected and observed

cumulative incidence of invasive

breast cancer among women who

received biennial screening vs

controls who received only a

prevalence screen at the end of their

observation period.

A, What would be expected

B, What was observed in our study:

Many are regressing spont.

Arch Intern Med. 2008;168(21):2311-

2316

invasive

breast

cancer

Similar to

Neuroblastoma

screening story:

The mammography paradox

(Baines 2003).

“An unacknowledged harm is that for up to 11 years after

the initiation of breast cancer screening in women aged 40-

49 years, screened women face a higher death rate from

breast cancer than unscreened control women, although

that is contrary to what one would expect”

Benefit is only 9%decrease in cancer death after 16 years, but facing

>2 X death from breast cancer by 3rd year1 seen:? Surgery speeds up

disease progression in young women! Surgery induced angiogenesis!

From Cancer support Assoc./"The Moss Reports", November 2005 newsletters.:

www.cancerdecisions.com.

Overall cumulative breast

cancer mortality rates

(aged 40–49 year) from

seven trials:

At 10 years of FU (over

800 000 person/years of

experience in each

group): cancer mortality

was not statistically

significantly reduced

The screened (40-49

aged ) are more likely

to die from Ca breast in

the first 11 years

Journal of the National Cancer

Institute, Vol. 95, No. 20,

October 15, 2003

Incidence of invasive

breast cancer

(per 100 000 women

in UK)

Overdiagnosis was

estimated at 52% (95%

confidence interval 46% to

58%).

BMJ 2009;339:b2587

doi:10.1136/bmj.b2587

BMJ 2009;339:b2587 doi:10.1136/bmj.b2587

Simple Patient Education sheet for screening

mammography made by H. Welch & William C. Black

Or:

Of every 10,000 tested with

mammography, 4 will have

cancer, 1 or more are over-

diagnosis and 250 false +ve

Mortality

RRR 20%

i.e. 4 instead

of 1000 (5o

yrs old)

screened for

10 yrs

invasive breast

cancer

LUNG CANCERS

Journal of the National Cancer Institute, Vol. 98, No. 11, June 7, 2006

RCT of MLP conducted among 9211 male smokers in the 1970s and

early 1980s 1983: no difference in lung Ca mortality but an excess of

46 cases in the screened.

The lung Ca status was investigated through 1999 of the 7118

participants in the MLP who were alive in 1983. From November 1971

through December 31, 1999, 585 in the intervention and 500 in the usual-

care arm diagnosed with lung cancer.

Conclusions: The persistence of excess cases in the intervention arm

after 16 additional years of follow-up provides continued support for

overdiagnosis in lung cancer screening

Similar to

Neuroblastoma

screening story:

British Journal of Cancer (2001)

84(1), 25–32

& J Natl Cancer Inst 2010;10:605–

613

By 3-year:

CT detection rate 11

times the expected

annual rate producing a

relative risk that

approached 1: 1.1 despite

the known RR of 15

lung cancers

Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer

The National Lung Screening Trial Research Team

Study Overview

In HIGH RISK participants who underwent initial screening in the NLCS Trial, low-dose CT showed positive results 3X as frequently as did CXR (27% vs. 9%) and detected more than twice as many stage I cancers (158 vs. 70).HIGH RISK Def: 55-74 yr old, > 30 pack years (former or current)

N Engl J Med, Volume 368(21):1980-1991, May 23, 2013

Enrollment and Follow-up of the Study Participants after the Initial Screening.

The National Lung Screening Trial Research Team. N Engl J Med 2013;368:1980-1991

CT CXR

The rate of +ve tests was 24.2% with LDCT and 6.9% with CXR. A

total of 96.4% & 94.5% of +ve results, resp. false +ve results.

LDCT: Incidence: 645 cases & 247 deaths/100,000 person-years

CXR: incidence: 572 & 309 deaths / 100,000 person-years

RRR in mortality by LDCT was 20.0% with annual CT (median 6.5

years, with a max. 7.4 years in each gp)

But:

Absolute rate: 1.4 vs. 1.7% dif. 0.33 %

With higher false +ve’s, risky work up, radiation,

8 RCT s &13 cohort studies of LDCT

screening: Three RCT chosenJAMA, June 13, 2012—Vol 307, No. 22

8 RCT s &13 cohort studies of LDCT

screening: Three RCT chosenJAMA, June 13, 2012—Vol 307, No. 22


The rate of melanoma

diagnosis tripled (from

7.9 per 100 000 to 21.5

per 100 00)

Death rate is stable

Such data suggest that

most of the increase in

diagnosis reflects

overdiagnosis.

Colorectal Cancer

• Tests: virtual colonography Incidentalomas

• Colonoscopy Overdx of polyps

• Screening Cancer death 8,83 to 5.88/1000

• But colonoscopy complications are 2.5/1000 (vs.

3/1000 saving!)

Crevical Cancer

• Pap smear Overdx & overRx of ? Precancer

lesions

• An Australian 15 yrs old on regular pap has 75%

chance of needing a colposcpy (cancer death is

0.2%) with high rates of interventions: cervical

freezing, laser, conization and even

hysterectomies..

• 37% of Whole body CT have abnormal findings that need

further tests.. ?10% an inidenteloma rate >99.5%

nonmalignant

• Examples:

RCC

solitary pulmonary nodules

ovarian cysts

Adrenal incidentaloma

Brain neoplasms

Proportion of patients with positive findings (■) and of patients with

follow-up recommendations (o) in 1192 Patients

Whole-Body CT

Screening:

Radiology 2005;

237:385–394

Organ % of

incidentaloma

on CT scan (a)

10 yr risk of

cancer death

(b)

Highest chance

of being lethat

Cancer =b/a

Chance it is not

a lethat Cancer

Lung

(smokers)

50% 1.8% 3.6% 96.4%

Lung

(Non-smokers)

15% 0.1% 0.7% 99.3%

Kidney 23% 0.05% 0.2% 99.8%

Liver 15% 0.08% 0.5% 99.5%

Thyroid

(by US)

67% 0.005% <0.01% >99.99%

Chance that an incidentaloma* represents a lethat Cancer for a typical

fifty year old From Overdiagnosed by H. G. Welch (quoted from multiple sources)

* Oversimplification is obvious on ignoring additional clinical and radiological data


A tumour that is frequently an incidenteloma!

The Main Reference

Conclusions

BMJ 2009;339:b3016


breast cancer

(per 100 000 women

in UK)

Overdiagnosis was



58%).

BMJ 2009;339:b2587

doi:10.1136/bmj.b2587

Cochrane Metanalysis7 eligible trials identified (500,000 in the 7 trials):

- 3 trials(c optimal random ): No reduction in mortality at 13 years

(RR 0.90, 0.79 to 1.02);

- 4 trials (suboptimal randomis): significant reduction in mortality,

RR of 0.75, CI 0.67 to 0.83). The RR for all 7 trials 0.81

No. of lumpectomies/mastectomies were larger in the screened, RR

1.31; radiotherapy similarly increased.

• For every 2000 women invited for screening over 10 yr:

1 life is prolonged and 10 unnecessary Rx

Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database

of Systematic Reviews 2009, Issue 4. Art. No.: CD001877. DOI:

10.1002/14651858.CD001877.pub3. & a lecture for Dr. Srinivas Chakravarthy.

e.g. Holter M or CTA cardiac is not a prevention step!

To be clear!

Conclusions

After 15 years of follow-up post 10 yrs screening period, there were 1320

diagnosed in the screened group and 1205 in the control group. The excess

detection of 115 cancers (was150 at the end of 10 yr) indicated an overdiagnosis

is 24% (115/475)

Incidence of invasive breast

cancer and carcinoma in situ

per 100 000 women in

Manitoba, Canada

BMJ 2009;339:b2587

doi:10.1136/bmj.b2587

No catch up tumour !



• Neuroblastoma > doubled (up to almost fivefold in the screened

group (<1 year))

No intervention to the screened who had localized tumors:

11 neuroblastomasparents out of 17 accepted (one stage III tumor) &

were assessed once per month X periods (4 to 27 months).

RESULTS:

The 11 tumors decreased in size. None of the tumors had completely

disappeared by the last observation day. it seems reasonable to adopt

a wait-and-see strategy, with careful observation, for selected stage I or

II tumors identified in infants screened at 6 months of age.

Spontaneous regression of localized neuroblastoma

detected by mass screening.Journal of Clinical Oncology, 1998; 16(4):1265-1269

What does a high median, 5-year, or 10

year survival mean?

We assme it means patients with bad

cancers are living longer

But, it may just mean that more people are

being told they have ‘cancer’H. Gilbert Welch

, Overdiagnosis bias


breast cancer

(per 100 000 women

in UK)

Overdiagnosis was



58%).

BMJ 2009;339:b2587

doi:10.1136/bmj.b2587

15 percent of men with a “normal” PSA

level had prostate cancer

n engl j med

350;22, may

27, 2004

Early diagnosis saves lives by

finding cancers before spread..

It improves survival..

..How accurate?

Length Bias (Sojourn Time):

• Length” refers to tumour’s presymptomatic period;

considered for breast Ca as more important than

lead time bias. Slower growing cancers (good

prognosis) are more likely to be detected by

screening.

• ? Contained on discussing overdiagnosis bias

n engl j med 367;21

nejm.org 2002 november

22, 2012

Awareness and screening aimed for early diagnosis of

cancer with the goals of reduction of the rate of late-

stage disease and cancer mortality.

Secular trends and clinical trials suggest that these

goals have not been met; national data of awareness

and screening demonstrate significant increases in

early-stage disease, without a proportional decline

in later-stage disease

JAMA Published online July 29, 2013

Unexpected Disappointment

Expected effect of screening on late stage cancer

H. Gilbert Welch

J Clin Oncol 19:3490-3499.

Mammography: when?

Based on HIP, NCI mammography screening for

>35 then in 1976 for > 50 (fear of radiation)

1988: for 40’s 19923:9/10 studies no death

reduction <50 1997: No benefit <50 but bec. of

politics: start from 40 then 2009: >50

Why we have higher proportion of advanced

breast cancer at presentation?

• Colleagues: because of our poor screening

program !

• But I believe, it is more because we have not

diluted our breast cancer by the early staged

cancer “many are overdiagnosis ?” as the US

data has shown in previous slides

Wikipedia

? Early diagnosis

saves lives by

finding cancers

before spread ?

overdiagnosis

inflates cancer

survival statistics

What does longer survival mean?

We assume it means delayed death..

But it may just mean earlier diagnosis

2 yrs 4yrs

If you have a group with 2/10 survived 5 yrs.. Then,

adding..

H. Gilbert Welch

Lead time bias

Lead time bias

Three scenarios of

changes over time

in incidence rates

associated with

widespread

screening usage

JAMA, October 21,

2009—Vol 302, No. 15

n engl j med 363;13, september 23, 2010

Among women 50 to 69 years old:

mammography prevent 2.4 deaths for every

100,000 person-years (2.4±4.1 95% C.I)

Societies Guidelines:

• The two studies showed low or no death reduction with great

morbidities

• US Preventive Services Task Force: the evidence is insufficient

cannot make a decision on screening; No for > 75 years.

• The American Urological Association supports the use of PSA-

based screening (PSA & DRE in >50; reduced age cutoff to about

40.

• The American Cancer Society (ACS) and the National

Comprehensive Cancer Network (NCCN): discussion with the

patient about the risk and benefits. But both support screening

with the PSA and DRE in >50 (40 by NCCN), 45 for high risk and>

10 year life expectancy ,

The mammography paradox

(Baines 2003).

“An unacknowledged harm is that for up to 11 years after

the initiation of breast cancer screening in women aged 40-

49 years, screened women face a higher death rate from

breast cancer than unscreened control women, although

that is contrary to what one would expect”

Benefit is only 9%decrease in cancer death after 16 years, but facing

>2 X death from breast cancer by 3rd year1 seen:? Surgery speeds up

disease progression in young women! Surgery induced angiogenesis!

From Cancer support Assoc./"The Moss Reports", November 2005 newsletters.:

www.cancerdecisions.com.

Using Autopsy Series To Estimate the Disease

"Reservoir" for Ductal Carcinoma in Situ of the

Breast: How Much More Breast Cancer Can We

Find?

Seven autopsy series: the median prevalence

of invasive breast cancer was 1.3% (range, 0%

to 1.8%) and the median prevalence of DCIS

was 8.9% (range, 0% to 14.7%). Prevalences

were higher among women likely to have been

screened (that is, women 40 to 70 years of

age).

Annals of Internal Medicine,127 (11): 1023

3 patterns emerged

after

inception of

screening

JAMA

Published

online July

29, 2013

Wikipedia

OVERDIAGNOSIS IN CANCER: HARD TO BELIEVE!

Heterogeneity of cancer progression: A new understanding

e.g. doubling time of breast cancers (the same size)

range from 1.2 months to 6.3 years

ERSPC

Extra 34 out of 58 screen-detected prostate

cancers/1000 men.

Overdiagnosis from PSA-detected cancer about

60% (34/58).

• But, insufficient follow-up for catch-up cancers to appear

( Welch & Black)

To be deleted

Limitations against the ERSP conclosion

• It is a gathering of several studies with

different protocols

• The 20% reduction is Just 0.4% reduction,

NNS of 1400 & NNT 48 are very high

To be deleted

Cochrane Rev.: Screening for prostate:

• Harms are minor to major in severity and duration.

• Major: overdiagnosis and overtreatment, infection, blood loss

requiring transfusion, pneumonia, erectile dysfunction, and

incontinence.

• Also, false +ve PSA test and overdiagnosis (up to 50% in

the ERSPC study).

To be deleted

N Engl J Med 2011;365:2013-9.

To be deleted

Radical prostatectomy versus watchful waiting

for prostate cancer

(2012 The Cochrane Collaboration review

published in Issue 2, 2012)

Two trials met inclusion criteria. Both prior to the widespread use of

PSA:

- One trial (N = 142), US: All cause mortality not significantly

different between RP and WW groups after 15 years of follow up

(Hazard Ratio (HR) 0.9 (95% CI: 0.56 to 1.43).

- The second trial (N = 695), Scandinavian: After 12 years: prostate

Ca mortality and metastases compared with WW (width CI) for all

estimates (risk difference (RD) -7.1% (95% CI -14.7 to 0.5); RD -

5.4% (95% CI -11.1 to 0.2); RD -6.7% (95% CI -13.2 to -0.2),

respectively).

To be deleted

• Compared to WW, RP increased the absolute risks of

erectile dysfunction (RD 35% and urinary leakage (RD

27%)

The existing trials provide insufficient evidence to

allow confident statements to be made about the relative

beneficial and harmful effects of RP and WW for patients

with localised prostate cancer.

To be deleted

PLCO

To be deleted

Limitations against the PLCO conclosions

• Fixed PSA of 4.0 ? lower or age adjusted

• Contamination: 52% (PSA screening in control

group : 40% first year; 52% by year 6)in the control (vs. 85%) had PSA within past few years modest increase in Ca detected (20%)

• Less than half of those with a positive screen result had a biopsy (D. Brooks)

• Follow up is short: average follow up was 11 years.

To be deleted

n engl j med, 350;22 www.nejm.org may 27, 2004

Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2

percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The

prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per

milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent

among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of

2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per

milliliter

Prostate Ca

present with

all PSA values

including 10%

rate with <1

To be deleted

BMJ

2011;342:d1539

doi:10.1136/bmj.d15

39

BMJ 2011;342:d1539

BMJ 2009;339:b2587

doi:10.1136/bmj.b2587

Even for invasive breast

Ca significant

overdiagnosis

BMJ 2009;339:b2587 doi:10.1136/bmj.b2587

A prospective historical cohort Norwegian study

• A prospective cohort study (1986-2005) for overdiagnosis of

invasive breast cancer in 39,888 Norwegian 50-69 years of age

• The risk of overdx of invasive breast Ca: 15 to 20 to 18 to 25%

(two approaches).

Screening 2,500 women 50 to 69 years of age biennially: 20

women were diagnosed with invasive breast cancer, one death

was prevented, and six to 10 additional women were

overdiagnosed. In addition, the incidence of advanced breast

cancer was similar in both the screened and unscreened groups.

• Including DCIS would further increase the rate of overdiagnosis

(<50% progress)

Ann Intern Med. 2012;156(7):491-499.

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Overdiagnosis in cancer

Health & Medicine