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

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”

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”

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."

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

Prostate Cancer Screening Studies - 2009

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

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

PSA Biopsy Thresholds(4.0 versus 2.5 ng/ml)

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

sens

itivi

ty

2.6

.69 .86p = 0.0001

1.4

4.1

1.4

6.1

0.9

2.6

6.1

4.1

adjusted for biasunadjusted

Results Age > 60

0

0.2

0.4

0.6

0.8

1

0 0.2 0.4 0.6 0.8 1

sens

itivi

ty

1-specificity

adjusted for biasunadjusted

4.1

1.1 2.1

6.1

10.1

1.1

2.1

4.1

6.1

10.1

.62 .72p = 0.008

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

Prob

abilit

y of

No

PSA

Prog

ress

ion

1.0.9.8.7.6.5.4.3.2.1

0.0

PSA correlates with 10-year progression-free survival rates

Freedland SJ. J Urol 174: 1276-81, 2005

Age to Start PSA Screening

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.

Age- Specific Median PSA

Age Group Median PSA (ng/ml)

40s 0.7

50s 0.9

60s 1.3

70s 1.7

If baseline PSA is > median for age group, the risk of cancer is 12- to 22-fold higher

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 3.9–6.1Age in 50s vs. 40s 2.3 1.6–3.5African-American heritage 1.2 0.9–1.5Family history 1.06 1.02–1.11

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

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

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

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

American Cancer Society, Cancer Facts & Figures 2005

Example of National Mortality Rate Trends

Denmark

“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

Pattern A: Prostate Cancer Mortality Lower than before PSA Era

Pattern B: Prostate Cancer Mortality Decreasing but Still Higher than Before PSA Era

Pattern C: Prostate Cancer Rate Still Increasing Constantly (18 of 38 Countries Examined)

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