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
Two paths forward or we can screen smarter
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
Establishing a baseline PSA at 60 predicts long-term prostate cancer mortality Analysis of 1167 samples from 1981-2 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
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
Multivariable risk assessment http://tinyurl.com/caprisk
Multivariable risk assessment http://www.prostatecancer-riskcalculator.com/via.html
CaP Risk Among Low-SES Men UCSF CAPRA Score Porten et al. J Urol 2010; 184:1931
Targeting the right populations CaPSURE CAPRA Score Porten et al. J Urol 2010; 184:1931
Targeting the right populations CaPSURE SFGH CAPRA Score Porten et al. J Urol 2010; 184:1931
Risk Assessment and Risk- Adapted Management Diagnosis Treatment
Overtreatment and undertreatment Cooperberg et al. J Clin Oncol 2010; 28:1117
Age and risk Bechis et al. J Clin Oncol 2011; 29:235
Overtreatment and undertreatment Bechis et al. J Clin Oncol 2011; 29:235
Treatment Variation Cooperberg et al. J Clin Oncol 2010; 28:1117
SPCG-4 trial: RP vs. WW Bill-Axelson et al. New Engl J Med 2011; 364:1708
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
PIVOT Trial Wilt T et al. NEJM 2012; 367:203
PIVOT Trial Wilt T. AUA 2011 Plenary Presentation.
PIVOT Trial Wilt T. AUA 2011 Plenary Presentation.
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
The UCSF-CAPRA Variable Level Points Variable Level Points PSA 6 0 T-stage T1/T2 0 6.1-10 1 T3a 1 10.1-20 2 % of biopsy cores 20.1-30 3 <34% 0 >30 4 positive >34% 1 Gleason (primary/ secondary) 1-3/1-3 0 1-3/4-5 1 Age <50 0 4-5/1-5 3 >50 1 Sum points from each variable for 0-10 score Cooperberg et al. J Urol 2005; 173:1938
CAPRA: Cancer-specific survival HR C-index 1.39 (1.31-1.48) = 0.80 # at risk 4892 1430 350 Cooperberg et al. JNCI 2009; 101:878
Surveillance: Recent Experiences Cooperberg et al. J Clin Oncol 29:3669, 2012.
Active Surveillance: UCSF Dall Era et al. Cancer 2008; 112:2664
Surveillance: Recent Experiences We need better biomarkers, imaging tests, and psychosocial interventions Cooperberg et al. J Clin Oncol 29:3669, 2012
Active Surveillance: UCSF Upgrading/upstaging based on preop criteria for surveillance Progression vs. undersampling? Conti et al. J Urol 2009; 181:1628
Active Surveillance: Anxiety Treatment decision driven by PSA velocity and anxiety velocity Change nomenclature? PUNLUMP IDLE Latini et al. J Urol 2007; 178:826
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
Cancer, epub 2012. Courtesy of Ruth Etzioni Treatment Changes Explain Only a Fraction of the Mortality Decline No treatment Treatment Cases diagnosed since 1975
Cancer, epub 2012. 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
What if we listened to the USPSTF?
The D Recommendation Moyer et al. Ann Intern Med, epub 2012.
D is the wrong conclusion!
D is the wrong conclusion!
A Decision Aid for the USPSTF
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
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.