SUO 2017: Trials, Trends, and Models: Synthesizing the Evidence on Prostate Cancer Screening

Washington, DC ( Dr. Pinsky gave an interesting talk summarizing the known evidence on PSA screening and his opinion on the future directions we should be following. Dr. Pinsky began his talk with a short summary on why PSA screening is such a controversial issue. Prostate cancer (PC) is the 3rd leading cause of cancer death in US men with ~27000 deaths per year. A large proportion of PC patients are asymptomatic and predicting aggressive disease, as opposed to indolent disease is still imprecise. Furthermore, the side effects of PC treatment are frequent, longstanding, and substantial. PC also imposes a large burden on the US health care system and the magnitude of screening is still questionable. These led to the highly debatable US task force recommendation back in 2012, giving screening a grade D and then changing it to grade C in 2017.

Dr. Pinsky continued and discussed the 3 largest and most known screening randomized trials – PLCO (US), ERSPC (Europe) and CAP (from UK), which eventually led to the famous ProtecT trial. The PLCO recruited approximately 37000 men in each arm, between the ages 55-74 and subjected them to screening with annual PSA and DRE. This study demonstrated a mortality relative rate of 1.04 (95% CI: 0.87-1.24) during a 15 year follow-up period. The biggest limitation of this trial was the contamination of the control arm, with 86% of the control arm patients being screened for PSA as well, thus making this trial a comparison of intensive PSA screening vs. non intensive screening.

The ERSPC trial enrolled patients from 8 European countries aged 55-69 and compared screening to non-screening as well. The mortality relative rate was 0.79 (95% CI: 0.69-0.91) with 1.28 PC deaths prevented for every 1000 men invited for screening. One PC death was averted per 27 additional PC cases diagnosed. The final mentioned trial was the UK CAP trial, which is a cluster randomized trial of PSA testing for PC. More than 196000 patients were enrolled in the intervention group and more than 218000 in the control group, in the ages of 50-69. The primary outcome was PC mortality at 10 years median follow-up time. The compliance with screening was 35% and rate of contamination in the control arm was low around 6%. The study outcomes should be reported in the near future.

Dr. Pinsky continued and showed that the trends of PC incidence (according to SEER data) were initially significantly increased in the 1990s, when PSA was incorporated for screening, and since 2012 (US task force recommendation) the incidence has been going down. Mortality however, has not changed much through the years and only slightly decreased in recent years.

Dr. Pinsky presented another study which was a joint analysis of the PLCO and ERSPC data, utilizing a “mean lead time” (MLT) as surrogate of screening intensity. This study showed a 7-9% reduction of PC mortality per year of MLT, and 25-30% reduction in PC mortality for screening as practiced in these trials. 

Most urological guidelines toady recommend screening in the right populations and only after implementation of shared decision making, discussing all potential risks and benefits with the patient. A survey study conducted in 2006-2007 in 198 men, demonstrated that 64% and 36% of the time the provider and the patient, respectively, raised the topic of PSA screening. The study also showed that most providers (73%) did recommend PSA screening, 26% had no opinion and only 1% was against it. However this trial was implemented well before the US task force recommendation. 

Dr. Pinsky concluded his talk with some words on the future of PSA screening. He stated that what we need is “Smarter screening”: knowing who to screen/biopsy and who to treat immediately or later. Shared decision making instead of universal screening is the key and the use of MRI to help us guide who to biopsy or not biopsy, should be encouraged. Reliable biomarkers guiding us on biopsy/treatment decision must be developed, and lastly, the use of active surveillance for the appropriate patients, should be increased.

Presented by: Paul Pinsky, PhD Division of Cancer Prevention, National Cancer Institute, Bethesda, MD

Written by: Hanan Goldberg, MD @GoldbergHanan Society of Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC
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