Cancer screening may discover many dormant, regressing, or slowly progressing tumors that would not have affected the screened individuals. Such findings with there therapies are obviously harmful. This lecture is highly based on the book "over diagnosed" by H. Gilbert Welch and was presented in 2013 to KFSH-Dammam physicians
2. 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
4. Pathways to Overdiagnosis
• Screening ( pseudodisease)
• Redefining cut-off values:
• Using very sensitive tests (e.g. imaging) in
those with symptoms:
• Incidentally made “incidentalomas”
BMJ
6. OVERDIAGNOSIS IN CANCER:
Outline:
• Introduction of overdx
• Screening bias
• Overdiagnosis in: Thyroid, Prostate, breast,
melanoma, lung, colon and cervical Ca..
- Incindentelomas
7. 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
8. Is it: To look for a cancer? Get screened!
N Engl J Med, Vol. 346, No. 14 April 4, 2002
V. strange: The
screened maintained
higher rates for both
early & late stages
9. Size
Spontaneous regression of
localized neuroblastoma
detected by mass screening.
Journal of Clinical Oncology, 1998;
16(4):1265-1269
cntrol VMA levek
Surgery
10. Disease reservoir for three cancers:
Just look harder
J Natl Cancer Inst 2010;10:605–613
11. 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
12. Cancer statistics!
How would ypu explain this phenomenon?
JAMA, May 10, 2006—Vol 295, No. 18
13. Rates of new diagnosis and death for five
types of cancer in the US, 1975-2005.
Adapted from Welch and Black12
BMJ |2JUNE, 2012 |VOLUME 344
Epidemic of Dx not of cancers !
14. Autopsy Series
• 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.
15. Which is increasing? By which type? Why?
Straight & horizontal despite
JAMA, May 10, 2006—Vol 295, No. 18
16. 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
17. Cancer
August
15, 2009
Straight & horizontal despite
a high resolution scale
Are we really saving
these patients with
thyroidectomies?
Or just harming?
18. 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
<40
>40
Excellent results even for those
presented clinically! Why to search
for it!
Journal of Cancer Epidemiology, Volume 2012, Article ID 641372, 11 pages
19. J Natl Cancer Inst Monogr 2012;45:146–151
J Natl Cancer Inst 2010;10:605–613
Large reservoir
Just biopsy more and more’’
12, 24,36 and you will find it
www.cancer.gov
20. Rx improvement and awareness
more apparently than screening effect
N Engl J Med 2011;365:2013-9.
• Lifetime risk of
prostate Ca :
16% (160K/yr),
med age 68
• Lifetime risk of
cancer death:
3% (29k/yr),
med age 80
21. Overdiagnosis in prostate screening : one death prevented to 20 or 50 or
to infinity number of men overdiagnosed
J Natl Cancer Inst 2009;101:1325–1329
22. Mortality Results from a Randomized Prostate-
Cancer Screening Trial, PLCO
nejm.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
24. 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)
25. 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
26. 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!
27. 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
29. 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)
30. 89 835 women, aged 40-59, randomly assigned to mammography (five annual
mammography) or control
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
31.
32. All cause mortality
Breast cancer specific mortality
Conclusion: Annual
mammography (age 40-59)
does not reduce mortality from
breast cancer (22% :106/484
were over-diagnosed)
Breast cancer specific mortality from
cancers diagnosed in screening period
33. Effect on mortality
Interpretation:
Screening for breast
cancer with
mammography is
unjustified..
Lancet 2000; 355: 129–34
34. • 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
35. Screening
Mammography &
Incidence of
Stage-Specific
Breast Cancer in
the United States,
1976–2008.
Why we have
higher proportion
of advanced
breast cancer at
presentation?
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
36. er 22, 2012
NEJM 367;21 nejm.org 2002 november 22, 2012
37. 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:
38. 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.
39. 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
40. 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
42. 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
44. 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
46. lung cancers
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
British Journal of Cancer (2001)
84(1), 25–32
& J Natl Cancer Inst 2010;10:605–
613
47. 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
48. Enrollment and Follow-up of the Study Participants after the Initial Screening.
CT CXR
The National Lung Screening Trial Research Team. N Engl J Med 2013;368:1980-1991
49. 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,
50. 8 RCT s &13 cohort studies of LDCT
screening: Three RCT chosen
JAMA, June 13, 2012—Vol 307, No. 22
51. 8 RCT s &13 cohort studies of LDCT
screening: Three RCT chosen
JAMA, June 13, 2012—Vol 307, No. 22
52. J Natl Cancer Inst 2010;10:605–613
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.
53. 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!)
54. 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..
55. • 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
56. Whole-Body CT
Screening:
Radiology 2005;
237:385–394
Proportion of patients with positive findings (■) and of patients with
follow-up recommendations (o) in 1192 Patients
57. Chance that an incidentaloma* represents a lethat Cancer for a typical
fifty year old From Overdiagnosed by H. G. Welch (quoted from multiple sources)
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%
* Oversimplification is obvious on ignoring additional clinical and radiological data
58. A tumour that is frequently an incidenteloma!
J Natl Cancer Inst 2010;10:605–613
62. 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
63. Cochrane Metanalysis
7 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.
64. To be clear!
e.g. Holter M or CTA cardiac is not a prevention step!
66. 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)
67. 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
68. No catch up tumour !
N Engl J Med, Vol. 346, No. 14 April 4, 2002
70. Spontaneous regression of localized neuroblastoma
detected by mass screening.
Journal of Clinical Oncology, 1998; 16(4):1265-1269
• 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.
71. 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
72. 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
73. 15 percent of men with a “normal” PSA
level had prostate cancer
n engl j med
350;22, may
27, 2004
74. Early diagnosis saves lives by
finding cancers before spread..
It improves survival..
..How accurate?
75. 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
76.
77. n engl j med 367;21
nejm.org 2002 november
22, 2012
78. Unexpected Disappointment
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
81. 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
82. 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
83. ? Early diagnosis
saves lives by
finding cancers
before spread ?
overdiagnosis
inflates cancer
survival statistics
Wikipedia
84. 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..
Lead time bias
H. Gilbert Welch
Lead time bias
85. Three scenarios of
changes over time
in incidence rates
associated with
widespread
screening usage
JAMA, October 21,
2009—Vol 302, No. 15
86. 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)
n engl j med 363;13, september 23, 2010
87. 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 ,
88. 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.
89. 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
90.
91. 3 patterns
emerged
after
inception of
screening
JAMA
Published
online July
29, 2013
92. OVERDIAGNOSIS IN CANCER: HARD TO BELIEVE!
Heterogeneity of cancer progression: A new understanding
Wikipedia
e.g. doubling time of breast cancers (the same size)
range from 1.2 months to 6.3 years
93.
94. 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
95. Limitations against the ERSP conclosion
To be deleted
• 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
96. 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
98. Radical prostatectomy versus watchful waiting
for prostate cancer
To be deleted
(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).
99. 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.
101. Limitations against the PLCO conclosions
To be deleted
• 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.
102. To be deleted
Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed Prostate in Ca
449 (15.2
percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of present 7 or higher. with
The
prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per
all PSA values
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 including those with 10%
values of
2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of rate 3.1 to with 4.0 ng <1
per
milliliter
n engl j med, 350;22 www.nejm.org may 27, 2004
107. 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.
Notes de l'éditeur
Figure 1 Use of Screening Mammography and Incidence of Stage-Specific Breast Cancer in the United States, 1976–2008. Panel A shows the self-reported use of screening mammography and the incidence of stage-specific breast cancer among women 40 years of age or older. Panel B shows the incidence of stage-specific breast cancer among women who generally did not have exposure to screening mammography — those younger than 40 years of age.
Figure 1 Enrollment and Follow-up of the Study Participants after the Initial Screening. A total of 490 lung cancers were diagnosed: 406 in participants with positive screening results (270 in the low-dose computed tomography [CT] group and 136 in the radiography group), 67 in participants with negative results (18 and 49, respectively), and 9 in participants who missed the screening (4 and 5, respectively), as well as an additional 8 cancers in participants who were ineligible for the initial screening but received a diagnosis of lung cancer during the screening period (5 and 3, respectively). If an inadequate examination was performed (e.g., because of its quality, the image was not interpretable) and no rescreening took place, the participant was considered not to have been screened.
