The document discusses prostate cancer screening, highlighting that it is the most common non-skin cancer in men with significant incidence and mortality statistics. It reviews the effectiveness of PSA screening, noting a decline in prostate cancer mortality, yet raises concerns about overdiagnosis and the necessity for individualized screening protocols. It concludes by emphasizing the importance of informed and shared decision-making in screening practices.

1. Prostate Cancer Screening
Brad Ekstrand, MD/PhD
California Cancer Care
Mills-Peninsula Health Services
San Mateo, CA

2. Prostate Cancer Statistics 2013
• Most common non-skin cancer in men
• Expected new cases in US = 238,590
• Expected deaths in US = 29,720
• Only 12.4 % of patients die of their disease
• 1 in 6 lifetime incidence for Caucasian males
• 1 in 5 lifetime risk for African-American males
• 1 in 34 lifetime risk of dying of prostate cancer
CA: A Cancer Journal for Clinicians
Volume 63, Issue 1, pages 11-30, 17 JAN 2013

3. Incidence Rates for Selected Cancers
United States, 1975 - 2009.
CA: A Cancer Journal for Clinicians
Volume 63, Issue 1, pages 11-30, 17 JAN 2013

4. April 1, 1996

5. Historical Observations Supporting
PSA Screening
• Decline in prostate cancer mortality since 1990s

6. Trends in Death Rate for Various Cancers
1930 - 2010

7. Historical Observations Supporting
PSA Screening
• Decline in prostate cancer mortality since 1990s
• Countries with higher screening rates have
greater declines in PC mortality
• Stage migration

8. Stage Migration From PSA Screening
Organ Regionally
Year Metastatic
Confined Advanced
1985 37% 19% 42%
2009 91% 4% 4%
SEER database

9. Historical Observations Supporting
PSA Screening
• Decline in prostate cancer mortality since 1990s
• Countries with higher screening rates have
greater declines in PC mortality
• Stage migration
• Numerous observational studies on regional,
national, and international level

10. Problems with Observational
Studies
• Other potential causes of declining mortality
– Better local therapy for early stage disease
– Better systemic therapy
• Stage migration = lead-time bias?
• Length-time bias
• Randomized controlled trials required to prove
effectiveness

11. Major Randomized Trials of
Prostate Cancer Screening
• Laval University study (Quebec)
– 46,000 men; 1988 - 1996
– Now largely ignored due to poor statistical analysis

12. Major Randomized Trials of
Prostate Cancer Screening
• Laval University study (Quebec)
– 46,000 men; 1988 - 1996
– Now largely ignored due to poor statistical analysis
• European Randomized Study of Screening for Prostate
Cancer (ERSPC)
– 9 countries; each had slightly different protocol
– Schroder et al (2009) NEJM 360:1320-8
• Prostate, Lung, Colon, Ovarian Cancer Screening Trial
(PLCO)
– USA; 10 mostly urban centers
– Andriole et al (2009) NEJM 360:1310-9

13. ERSPC vs PLCO Trials
Design
ERSPC PLCO
182,160
# enrolled 76,693
(core 162,243)
50-74
Age range 55-74
(core 55-69)
PSA Frequency Average q 4 yrs q 1 yr x 6 yrs
2.5 – 4.0
PSA cutoff 4.0
(most 3.0)
DRE Offered? Variable Mandated (x4 yr)

14. ERSPC vs PLCO Trials
Results
ERSPC PLCO
Median f/u 9 yr 7 yr
Contamination 44% had prior PSA
20% (8-29%)
Rate 52% during trial
Compliance with
82% 85%
Screening
Biopsy if
80-90% 32% within 1 yr
indicated

15. ERSPC vs PLCO
Prostate Cancer Incidence
ERSPC PLCO
Screen Control Screen Control
Cancers 5590 4307 2820 2322
Cum. Incidence 8.2% 4.8% 7.4% 6.1%
Rate/1000 p-y 9.3 5.5 11.6 9.5
Rate Ratio
1.71 (1.32 – 2.33) 1.22 (1.16 – 1.29)
(95% CI)

16. ERSPC vs PLCO
Prostate Cancer Incidence
ERSPC PLCO
Screen Control Screen Control
Cancers 5590 4307 2820 2322
Cum. Incidence 8.2% 4.8% 7.4% 6.1%
Rate/1000 p-y 9.3 5.5 11.6 9.5
Rate Ratio
1.71 (1.32 – 2.33) 1.22 (1.16 – 1.29)
(95% CI)

17. ERSPC vs PLCO
Prostate Cancer Mortality
ERSPC PLCO
Screen Control Screen Control
Patients 82,816 99,184 38,343 38,350
PC Deaths 261 363 50 44
Rate/1000 p-y 0.35 0.41 0.20 0.17
Rate Ratio
0.80 (0.65 – 0.98) 1.13 (0.75 – 1.7)
(95%CI)

18. ERSCP vs PLCO
Prostate Cancer Deaths
ERSCP PLCO

19. Criticism of the PLCO Study
• Low-risk group of patients: 44% had PSA
before study entry
• Low number of prostate cancer deaths
• Shorter follow up
• Underpowered
– Few Events
– 52% contamination of controls
– Poor compliance with biopsy
Stephenson AJ; ASCO 2010

20. Criticism of ERSPC Study
• Wide confidence intervals; p = 0.04
• Variable benefit seen in different age groups
• Differences in treatment of cancers between
arms
• Relatively small # of PC deaths

21. Overdiagnosis
• To prevent 1 PC death in 10 yr:
– 1410 men screened
– 48 men diagnosed and treated for PC
– Breast Cancer: 1339 screen and 10 treat

22. Harm from Screening
• Hospitalization from biopsy complication 1%
• Biopsy pain 55%
• Psychological burden: stigma, PSA anxiety
• Risks of Therapy:
– Incontinence
– Erectile dysfunction
– Bowel effects
– Metabolic Syndrome
– Osteoporosis
• $$$ of case finding and treatment substantial

23. Unresolved Questions
• Should PSA screening be done at all?
• Who should be screened?
• When to start?
• When to stop?
• How often?
• When to do a biopsy?
– Single PSA cutoff is arbitrary
– Confirmatory PSA test?
– Multivariable calculators
– New biomakers (e.g. PCA3)

24. Guidelines
AUA ACS USPSTF
Shared Decision- Yes Yes
Yes
Making? (use decision aid) (if requested)
Age to begin offering
Average Risk pt 40 50 N.A.
High Risk pts 40 40-45 N.A.
PSA;
Screening Tests PSA + DRE N.A.
(DRE optional)
Frequency Annual Annual N.A
Age, Fam Hx,
Race, DRE, total PSA >4.0 or abn
Criteria for Biopsy N.A.
PSA, PSA velocity DRE
+ more
Adapted from Hoffman RM (2011) NEJM 365:2013-2019

25. Conclusions
• PSA is not a robust screening test
• Marginally effective in reducing PC mortality
• Risk of overdiagnosis is extremely high
• ACS Guidelines represent a balanced view
• Informed and shared decision-making is
mandatory, but takes time
• All cancer screening needs to be individualized