prostate cancer screening in 2013: reports of its death are greatly exaggerated norm d. smith, m.d....
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Prostate Cancer Screening in 2013: Reports of its Death Are
Greatly Exaggerated
Norm D. Smith, M.D.Associate Professor
Co-DirectorUrologic Oncology
University of Chicago
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United States Preventive Services Task Force (USPSTF)
USPSTF Warns Against Blood Test For Prostate Cancer
ABC World News - “An earthquake today in the debate over men and prostate cancer”
New York Times "PSA does not save lives, but results in needless medical procedures that have left tens of thousands of men impotent, incontinent or both”
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United States Preventive Services Task Force (USPSTF)
Los Angeles Times -16-member panel determined whether widespread PSA testing saves enough lives to justify the considerable medical fallout
HealthDay - the task force studied "five trials, the two largest done in Europe and in the United States... found no reduction in deaths due to prostate cancer among men of all ages in the study who underwent PSA testing”
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United States Preventive Services Task Force (USPSTF)
New York Times - Aetna and Kaiser Permanente said it was unclear whether they would continue paying for the test… United Healthcare and WellPoint said they would continue coverage
GQ Medicare "is required under a 2008 law to cover the PSA test annually for beneficiaries 50 years old and older. Presumably it would take an act of Congress to undo that coverage requirement. Medicaid coverage of the PSA test is a state by state decision."
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United States Preventive Services Task Force (USPSTF)
No Urologists Grade D recommendation against PSA-
based screening for prostate cancer “moderate or high certainty that the
service has no net benefit… harms outweigh the benefits”
Discourage PSA screening
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Prostate Cancer Screening Studies - 2009
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Prostate Test Found to Save Few Lives(New York Times, March 2009)
Last week, two major studies from the United States and Europe found that P.S.A. testing — the annual blood test used to screen men for prostate cancer — saves few if any lives, while exposing patients to aggressive and unnecessary treatments that can leave them impotent and incontinent
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Prostate-Specific AntigenBest Practice Statement:
2009 Update(American Urological Association)
http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf
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PSA Biopsy Thresholds(4.0 versus 2.5 ng/ml)
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0.9
Results Age < 60
0
0.2
0.4
0.6
0.8
1
0 0.2 0.4 0.6 0.8 1
1-specificity
sen
siti
vity
2.6
.69 .86p = 0.0001
1.4
4.1
1.4
6.1
0.9
2.6
6.1
4.1
adjusted for bias
unadjusted
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Results Age > 60
0
0.2
0.4
0.6
0.8
1
0 0.2 0.4 0.6 0.8 1
sen
siti
vity
1-specificity
adjusted for bias
unadjusted 4.1
1.1 2.1
6.1
10.1
1.1
2.1
4.1
6.1
10.1
.62 .72p = 0.008
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T1c Patients with RRP by PSA at Diagnosis ( PSA Follow-up Study)
2.6-4.04.1-6.06.1-9.9> 10
Number of Months
120100806040200
Pro
babili
ty o
f N
o P
SA
Pro
gre
ssio
n
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.10.0
PSA correlates with 10-year progression-free survival rates
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Freedland SJ. J Urol 174: 1276-81, 2005
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Age to Start PSA Screening
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Baltimore Longitudinal Study on Aging
Median PSA level: Age 40-49 = 0.6 ng/ml Age 50-59 = 0.7 ng/ml 3-fold higher risk of prostate cancer within
10-25 years if PSA > median for age group
Fang et al. Urology, 58: 411, 2001.
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Age- Specific Median PSA
Age Group Median PSA (ng/ml)
40s 0.7
50s 0.9
60s 1.3
70s 1.7
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If baseline PSA is > median for age group, the risk of cancer is 12- to 22-fold higher
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Odds Ratio of Subsequent Prostate Cancer Diagnosis
Loeb S, Roehl KA, Antenor JA, Catalona WJ, Suarez BK, Nadler RB. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer in men younger than 60 years old. Urology. 2006;67(2):316-20.
Variable OR 95% CI
Any baseline PSA >0.7 ng/mL for men 40–49 yr
30.9 4.2–229.4
Baseline PSA between 0.7 and 2.5 ng/mL for men 40–49 yr
14.6 1.9–113.7
Any baseline PSA >0.9 ng/mL for men 50–59 yr
13.2 9.9–17.4
Baseline PSA between 0.9 and 2.5 ng/mL for men 50–59 yr
7.6 5.7–10.2
Suspicious vs. negative DRE 4.9 3.9–6.1
Age in 50s vs. 40s 2.3 1.6–3.5
African-American heritage 1.2 0.9–1.5
Family history 1.06 1.02–1.11
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PSA Kinetic Parameters
PSA Velocity absolute change in PSA per year Independent of baseline PSA value Better for diagnosis
PSA Doubling Time Time it takes PSA value to double A function of baseline PSA (the higher the
baseline, the longer it takes to double) Not as useful for diagnosis
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Median PSAV
(ng/ml/yr)
Cancer 0.8
Non-Cancer Biopsy
0.1
No Biopsy 0.1
PSA Velocity in PSA Study
P<0.0001
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PSA Velocity for Detecting Life-Threatening PCa when Still Curable
For men with a consistent PSAV of >0.35 ng/ml/year, there is more than a 5-fold increased risk of PCa death in next 2-3 decades
Recommended to begin PSA testing at age 40 to acquire reliable PSAV data
Carter HB et al JNCI 2006;98:1521-7
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OR(95% CI) p-value
PSAV > 0.4 6.06 (5.19-7.08) <0.0001
Total PSA (per unit) 1.08 (1.05-1.10) <0.0001
Age (per year) 1.04 (1.03-1.05) <0.0001
AA vs Caucasian 1.57 (1.19-2.07) 0.002
Family history 1.25 (1.03-1.52) 0.02
Multivariate analysis to predict prostate cancer detection
AUC=0.80
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American Cancer Society, Cancer Facts & Figures 2005
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Example of National Mortality Rate Trends
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Denmark
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“The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer.”
Example of WHO Global Mortality Rate Trends
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Pattern A: Prostate Cancer Mortality Lower than before PSA Era
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Pattern B: Prostate Cancer Mortality Decreasing but Still Higher than Before PSA Era
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Pattern C: Prostate Cancer Rate Still Increasing Constantly (18 of 38 Countries Examined)
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Take Home Messagesfor PSA Screening
Initial PSA screening at age 40 If PSA higher than median for age,
annual screening at minimum (perhaps 6 months)
Annual PSA screening at 40 for African-Americans and men with family history
Biopsy threshold 2.5 in men < 60 Consider biopsy for PSA velocity > 0.35 PSA screening likely saves lives