Long‐term consequences of the USPSTF Grade D recommendation for prostate‐specific antigen screening

Abstract

In 2012, the US Preventive Services Task Force (USPSTF) issued a Grade D recommendation to prostate cancer screening with prostate-specific antigen (PSA) testing for men of all ages. This low mark represents a recommendation against any routine screening at all and was an extension of a previous 2008 Grade D recommendation for men 75 years of age. This action signaled the USPSTF’s belief that “there is moderate or high certainty that the [screening] has no net benefit or that the harms outweigh the benefits.” Eight years later, in this issue of Cancer, Butler et al shed light on the repercussions of the Grade D recommendation and the natural experiment that was made possible by this move. In 2009, 2 major prospective trials on PSA screening were published: The European Randomized Study of Screening for Prostate cancer (ERSPC) trial and the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial conducted in the United States. The PLCO trial showed no mortality benefit for PSA screening at 10 years, whereas the ERSPC trial demonstrated a 20% reduction in prostate cancer mortality at 9 years, though PSA screening was associated with a very high rate of overdiagnosis. The Grade D recommendation was largely based on these trials, with a particular emphasis on the negative outcomes of the PLCO trial. The reliance on these studies was flawed for 2 reasons. First, the PLCO trial faced heavy criticism due to design constraints and high levels of crossover between study arms; specifically, there was a very high rate of control arm PSA testing. Instead of being a trial of screening versus nonscreening, it ended up testing organized screening versus opportunistic screening and found no difference after 15 years of follow-up. At the same time, the cleaner ERSPC trial continued to show a mortality benefit for PSA screening as of their last reporting, 13 years out. Second, the USPSTF took the position that the inconsistent mortality benefit results were not meaningful enough to balance the significant harms of prostate cancer overtreatment. At first blush, this reasoning appears well-founded. Overtreatment is certainly a major problem for low-risk prostate cancer, and specialists have long recognized that all prostate cancer treatments (surgery, radiation, ablation) can have significant adverse effects in sexual, urinary, and bowel function. Higher-risk prostate cancer, however, remains a leading cause of cancer-related death in American men—meaning that for many men, early treatment could be a lifesaver. Consequently, many researchers and clinicians have dedicated their professional careers to study and mitigate the risks associated with prostate cancer treatment. Examples of progress on this front include improved shared decision-making, increased use of active surveillance for low-risk prostate cancer, and improved surgical and radiotherapy techniques. In fact, use of monitoring for low-risk prostate cancer patients has risen precipitously in the past 5 years. However, the USPSTF’s decision ignored these nuances. By summarily rejecting any benefits of PSA screening in favor of highlighting treatment toxicities, the USPSTF ignored the extensive work being done to mitigate these toxicities. The proverbial baby was thrown out with the bathwater. Unsurprisingly, the recommendation sent shockwaves through the urologic oncology community. Clinicians and patient advocates pushed back, arguing that the Grade D recommendation was shortsighted and represented a form of “screening nihilism.” The impact of the recommendation was swift. PSA screenings throughout the United States began to decrease, and there was a concomitant decrease in prostate cancer incidence. For example, screening in men aged 50-59 years dropped by almost 10% between 2010 and 2013. At the same time, new incident prostate cancer diagnoses dropped by 12.2% in the month following the USPSTF draft guidelines and decreased 28% overall in the year following the USPSTF recommendation. Although these early reports did not find any changes in metastatic disease presentation,