Prostate Cancer Screening 2012:

Transcription

1 Prostate Cancer Screening 2012: Next Steps to End the PSA Controversy Matthew R. Cooperberg, MD,MPH Advanced Robotic Urology and Prostate Cancer Update Napa, CA August 2, 2012

2 Two paths forward or we can screen smarter

3 Rationale for earlier screening (AUA) A baseline PSA level above the median for age 40 is a strong predictor of prostate cancer The age adjusted mortality rate for prostate cancer between ages 55 and 64 is significant. Such men may have been cured by earlier diagnosis and treatment Younger men are more likely to have curable cancer PSA is a more specific test for cancer in younger men Earlier and less frequent testing might reduce mortality and costs compared to annual testing beginning later Patients at risk for, but who do not have cancer may be candidates for chemoprevention Greene et al. J Urol 2009; 182:2232

4 Establishing a baseline PSA at 60 predicts long-term prostate cancer mortality Analysis of 1167 samples from matched to Malmö registry data 11.4% diagnosed, 2.7% died of prostate cancer If PSA <1.0 at age 60, likelihood of prostate cancer death <0.3% 90% of prostate cancer deaths occurred in men with PSA >2.0 (top quartile) Vickers et al. BMJ 341, 2010

5 An interesting perspective What seems to be missing from most of the PSA discussion is that the majority of men will have a normal PSA value and they will be reassured A normal PSA level offers peace of mind, a valued commodity in a world that is frequently full of troubling news. Detsky et al. JAMA 307:1035, 2012

6 Multivariable risk assessment

7 Multivariable risk assessment

8 CaP Risk Among Low-SES Men UCSF CAPRA Score Porten et al. J Urol 2010; 184:1931

9 Targeting the right populations CaPSURE CAPRA Score Porten et al. J Urol 2010; 184:1931

10 Targeting the right populations CaPSURE SFGH CAPRA Score Porten et al. J Urol 2010; 184:1931

11 Risk Assessment and Risk- Adapted Management Diagnosis Treatment

12 Overtreatment and undertreatment Cooperberg et al. J Clin Oncol 2010; 28:1117

13 Age and risk Bechis et al. J Clin Oncol 2011; 29:235

14 Overtreatment and undertreatment Bechis et al. J Clin Oncol 2011; 29:235

15 Treatment Variation Cooperberg et al. J Clin Oncol 2010; 28:1117

16 SPCG-4 trial: RP vs. WW Bill-Axelson et al. New Engl J Med 2011; 364:1708

17 PIVOT Trial 52 centers over 7 years screened 13,022 pts to find 5023 eligible and accrue 731 (14.5% of eligible, more likely Af-Am, low grade) Wilt T et al. NEJM 2012; 367:203

18 PIVOT Trial Wilt T et al. NEJM 2012; 367:203

19 PIVOT Trial Wilt T. AUA 2011 Plenary Presentation.

20 PIVOT Trial Wilt T. AUA 2011 Plenary Presentation.

21 Prostate Cancer Risk Assessment Goal: inform physician-patient decisions about optimal initial treatment approach and timing Active surveillance Early local therapy Multimodal therapy Systemic therapy

22 The UCSF-CAPRA Variable Level Points Variable Level Points PSA 6 0 T-stage T1/T T3a % of biopsy cores <34% 0 >30 4 positive >34% 1 Gleason (primary/ secondary) 1-3/ /4-5 1 Age < /1-5 3 >50 1 Sum points from each variable for 0-10 score Cooperberg et al. J Urol 2005; 173:1938

23 CAPRA: Cancer-specific survival HR C-index 1.39 ( ) = 0.80 # at risk Cooperberg et al. JNCI 2009; 101:878

24 Surveillance: Recent Experiences Cooperberg et al. J Clin Oncol 29:3669, 2012.

25 Active Surveillance: UCSF Dall Era et al. Cancer 2008; 112:2664

26 Surveillance: Recent Experiences We need better biomarkers, imaging tests, and psychosocial interventions Cooperberg et al. J Clin Oncol 29:3669, 2012

27 Active Surveillance: UCSF Upgrading/upstaging based on preop criteria for surveillance Progression vs. undersampling? Conti et al. J Urol 2009; 181:1628

28 Active Surveillance: Anxiety Treatment decision driven by PSA velocity and anxiety velocity Change nomenclature? PUNLUMP IDLE Latini et al. J Urol 2007; 178:826

29 So what explains this graph? 40% drop in age-adjusted prostate cancer mortality since early 1990s Siegel et al. CA Cancer J Clin 2012; 62:10

30 Cancer, epub Courtesy of Ruth Etzioni Treatment Changes Explain Only a Fraction of the Mortality Decline No treatment Treatment Cases diagnosed since 1975

31 Cancer, epub Courtesy of Ruth Etzioni Mortality Trends Suggest a Clear Role for PSA Screening No treatment Treatment Treatment and screening ERSPC benefit Cases diagnosed since 1975

32 What if we listened to the USPSTF?

33 The D Recommendation Moyer et al. Ann Intern Med, epub 2012.

34 D is the wrong conclusion!

35 D is the wrong conclusion!

36 A Decision Aid for the USPSTF

37 How to save the baby: screen smarter Start earlier (e.g., 40) but see below! Screen less frequently if baseline is low Focus on populations at highest risk Screen for high-risk prostate cancer, don t over-treat low-risk disease Embrace active surveillance Fix incentives Refer early and wisely Change nomenclature Continue to develop novel biomarkers

38 Conclusions Screening saves lives, period. The USPSTF analysis downplays benefits, overestimates harms, and is predicated on far too short of a time horizon. Overtreatment is without question a major public health problem. But the answers lie in smarter screening and better treatment decisions, not in wholesale cessation of screening.