Prostate cancer is a global killer Prostate Cancer 2016 Since 2008, up from 258,000 Smarter Screening and Risk-Adapted Treatment Now passed esophageal Matthew R. Cooperberg, MD, MPH @dr_coops Departments of Urology and Epidemiology & Biostatistics Incidence Mortality 44 th Annual Advances in Internal Medicine T orre et al. CA Cancer J Clin 65:87, 2015 May 25, 2016 Departm ent of Urology The Good News in the U.S.: So how did we end up here? >50% drop in age-adjusted prostate cancer mortality since early 1990s Siegel et al. CA Cancer J Clin 2016; 66:7 Moyer et al. Ann Intern Med 157:120, 2012. Departm ent of Urology Departm ent of Urology 1
Prostate cancer is heterogeneous This is (mostly) our fault. Esserman et al. JAMA 2009; 302:1685 Departm ent of Urology Goal: Prostate Cancer Risk Assessment Goal: inform physician-patient decisions about optimal initial treatment approach and timing What do the trials (really) tell us? Active surveillance Early local therapy Multimodal therapy Systemic therapy Departm ent of Urology 2
PLCO PLCO Prostate, Lung, Cancer, & Ovarian Cancer Screening Trial • 76,693 men aged 55-74 randomly assigned to annual PSA screening for 6 years vs. “usual care” at 10 U.S. centers 1993-2001 “…the study was not a fair comparison between • “52”% of men in the “usual care” group had at least one screening and no screening; instead, it was a PSA test drawn comparison between annual and ad hoc screening.” – Cooperberg and Carroll, NEJM 2009; 361:203 • Only 30-40% of men with high PSAs had biopsies • Virtually no difference between types of tumors seen in screening vs. usual care groups Andriole et al. NEJM 2009; 360:1310 Andriole et al. NEJM 2009; 360:1310 Departm ent of Urology Departm ent of Urology PLCO: the contamination problem PLCO: Update Data from surveys of the “control” arm of the PLCO study: Pinsky et al. Clin Trials 2010; 7:303 Andriole et al. J Natl Cancer Inst 2012; 104:1 Departm ent of Urology Departm ent of Urology 3
PSA testing in the PLCO “control” arm PSA testing in the PLCO “control” arm PLCO was not a trial of screening vs. no screening Meta-analysis including PLCO is invalid ! Shoag et al. N Engl J Med 2016; 374:1795 Shoag et al. N Engl J Med 2016; 374:1795 Departm ent of Urology Departm ent of Urology ERSPC ERSPC European Randomized Study of Screening for Prostate Cancer • Population-based trials at 7 European centers • 182,160 men age 50-74 randomized (162,387 in core age 55-69) • Screening interval 4 years at most centers (2 at one) • 21% risk reduction for cancer-specific mortality with screening (up to 38% in years 10-11) • 29% risk reduction with adjustment for noncompliance • Initial NNS 1410, NNT 48 Schröder et al. NEJM 2009; 360:1320 Schröder et al. NEJM 2009; 360:1320 Departm ent of Urology Departm ent of Urology 4
Taking the long view on screening ERSPC: update Short-Term Long-Term Lives saved 0.7 6 A guideline based on Overdiagnoses 34 42 outcomes at 8 or 10 years is completely meaningless! Overdiagnoses/Live 48 7 s saved Rate ratio 0.73-0.79 for prostate cancer mortality, NND 27 Schröder et al. Lancet 2014; 384:2027 Gulati et al. J Clin Epidemiol 64:1412, 2011 Departm ent of Urology Departm ent of Urology The Göteborg randomized trial The Göteborg randomized trial • Göteborg vs. PLCO & ERSPC • Younger mean at start of screening RR 0.56 (0.39-0.82, p=0.002) RR 0.56 (0.39-0.82, p=0.002) • Lower PSA threshold for referral NNS: 293, NNT: 12 • Q2 year interval • Higher rate of biopsy among those with high PSA • Lower early rates of PSA contamination • Longer followup (though still relatively short) • 44% of men were managed with initial surveillance Hugosson J. Lancet Oncol 2010; 11:725 Hugosson J. Lancet Oncol 2010; 11:725 Departm ent of Urology Departm ent of Urology 5
Even Göteborg now faces contamination Did the USPSTF assess harms fairly? “Adequate evidence shows that up to 5 in 1000 men will die within 1 month of prostate cancer surgery and between 10 and 70 men will have serious complications but survive. Radiotherapy and surgery result in long-term adverse effects, including urinary incontinence and erectile dysfunction in at least 200 to 300 of 1000 men treated with these therapies. Radiotherapy is also associated with bowel dysfunction” Arnsrud Godtman. Eur Urol 2015; 68:354 Moyer et al. Ann Intern Med 157:120, 2012. Departm ent of Urology Departm ent of Urology Over-treatment and under-treatment The real problems: Over- and under-screening, Over- and under-treatment Cooperberg et al. J Clin Oncol 2010; 28:1117 Departm ent of Urology 6
Treatment by risk and age And too much care is by low-volume providers Bechis et al. J Clin Oncol 2011; 29:235 Savage et al, J Urol 2009 182:2677 Departm ent of Urology Departm ent of Urology Who gets screened? 2000-05 Who gets screened? 2012-13 Drazer et al. J Clin Oncol 2011; 29:1736 Sammon et al. JAMA Intern Med 174:1839, 2014 Departm ent of Urology Departm ent of Urology 7
It’s even worse than that Does the USPSTF Recommendation Matter? The AUA, EAU, ACS, ASIM, and NCCN all recommend some variation on shared decision making. Walter et al. JAMA 2006; 296:2336 T asian et al. Urol Oncol 30:155, 2012 Departm ent of Urology Departm ent of Urology Does the USPSTF Recommendation Matter? This time seems to be different National Health Interview Survey (NHIS) Prasad et al. JAMA 307:1692, 2012 Siegel et al. CA Cancer J Clin 2016; 66:7 Departm ent of Urology Departm ent of Urology 8
This time seems to be different This time seems to be different JAMA 314:2054, 2015 JAMA 314:2054, 2015 Jemal et al. JAMA 2015; 314:2054 Jemal et al. JAMA 2015; 314:2054 Departm ent of Urology Departm ent of Urology This time seems to be different The disproportionate weight of the USPSTF Barocas et al. J Urol epub 2015 Departm ent of Urology Departm ent of Urology 9
What explains this curve? What if we really listen to the USPSTF? No treatment Treatment Treatment and screening ERSPC benefit ~60,000 avoidable deaths 2013-2025 Etzioni et al. Cancer 2012; 118:5955 Gulati et al. Cancer 2014; 120:3519 Departm ent of Urology Departm ent of Urology Would the USPSTF at least save money? Where do we go from here? Departm ent of Urology 10
Or can we do it all better? PSA should not be interpreted in a vacuum The value of establishing an early baseline • 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) http://tinyurl.com/caprisk Vickers et al. BMJ 341:c4521, 2010; Vickers et al BMJ 346:f2023, 2013 Departm ent of Urology Departm ent of Urology 11
Don’t underestimate reassurance “Simple schema” for SDM “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.” Vickers et al. Ann Intern Med 2014; 161:441 Detsky et al. JAMA 307:1035, 2012 Departm ent of Urology Departm ent of Urology Risk stratification works! So we can tell the rabbits from the turtles The UCSF-CAPRA score C-index = 0.79 Sum of points from each variable for 0-10 score Validated in 14 studies on 4 continents, N>20,000 http://urology.ucsf.edu/capra.html Cooperberg et al. J Urol 173:1938, 2005 Departm ent of Urology Departm ent of Urology 12
Precision medicine 2016 Don’t treat most low-risk disease Draw PSA ? • SNPs? • PCA3 1 s t biopsy? • phi • 4K score • ConfirmMDx • PCA3 2 nd biopsy? • phi • 4K panel • OncoType Pre- treatment • Prolaris • Decipher Post-op • Prolaris treatment? MRI • OncoType PSMA-PET/CT Advanced • ARv7? disease Wilt T et al. NEJM 2012; 367:203 Departm ent of Urology Departm ent of Urology Active Surveillance: Anxiety Times are changing – fast Treatment decision driven by PSA velocity and “ anxiety velocity ” Change nomenclature? PUNLUMP IDLE Latini et al. J Urol 2007; 178:826; Esserman and Thompson, JAMA 2013 Departm ent of Urology Departm ent of Urology 13
Surveillance is gaining in the real world Times are changing – fast Womble et al. Eur Urol epub 2014. Cooperberg and Carroll. JAMA 2015 314:80 Departm ent of Urology Departm ent of Urology Older men with high-risk tumors should be treated Trends for men ≥75 years old aggressively Cooperberg and Carroll. JAMA 2015 314:80 Lu-Yao et al. JAMA 2009, 302:1202 Departm ent of Urology Departm ent of Urology 14
“Noncontroversial” statements re: high-risk Do treat most high-risk disease • RP is more effective than WW (PIVOT) • RT+ADT is more effective than ADT (NCIC/PR07) • RT+ADT is more effective than RT (many RCTs) • ADT monotherapy is only marginally more effective than WW (Lu-Yao 2008) • Adding early postop RT to RP improves survival for locally advanced cases (3 RCTs) Wilt T et al. NEJM 2012; 367:203 Departm ent of Urology Departm ent of Urology What about RP vs. RT? No RCTs but… Predicted 15-year CSM Wallis et al. Eur Urol epub 2015 Cooperberg et al. AUA 2015 Departm ent of Urology Departm ent of Urology 15
Recommend
More recommend
