An updated Cochrane review has found that prostate-specific antigen (PSA) screening probably reduces deaths from prostate cancer — a notable shift from the influential group’s 2013 conclusion that screening did not significantly lower prostate cancer mortality. 

The new analysis, based on longer follow-up and additional trial data, suggests that PSA screening reduces prostate cancer deaths by about 2 per 1000 men screened. However, this modest benefit comes at the cost of an increased number of prostate cancer diagnoses, many of which are localized cancers that may never have become clinically significant.

“With new data now available, we can now say with moderate certainty that PSA screening reduces prostate cancer deaths in men with a sufficient life expectancy,” senior author Philipp Dahm, MD, from the University of Minnesota in Minneapolis, said in a news release. 

However, the results are “not a blanket endorsement of universal screening,” explained first author Juan Franco, MD, with Heinrich Heine University in Düsseldorf, Germany. Given that PSA screening increased diagnoses of early-stage disease, the benefits of screening must still be weighed against the risks of overdiagnosis and overtreatment.

That’s why Gilbert Welch, MD, chooses not to undergo screening. “The reason is simple — it strikes me as a bad deal,” Welch, who was not involved in the review, told Medscape Medical News. 

The chance of benefit is very small, whereas “the chance of being harmed is considerably larger” and begins as soon as screening starts, said Welch, a general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston.

The PSA Trade-Offs

Prostate cancer remains one of the most common malignancies among men worldwide, with an estimated 1.5 million new cases and nearly 400,000 deaths globally in 2022. PSA testing has long been controversial because although it can detect cancers earlier, it also identifies many slow-growing tumors that may never cause symptoms or be life-threatening. Treating these indolent cancers can expose men to urinary incontinence, erectile dysfunction, bowel problems, and psychological distress.

The updated Cochrane review included six randomized controlled trials of screening vs no screening involving a total of 789,086 men aged 45-80 years in Europe and North America. 

The latest analysis differs from the 2013 review in that it included the large UK CAP trial conducted between 2002 and 2021 (with 15 years of follow-up) and incorporated up to 23 years of follow-up from earlier studies, notably the European Randomized Study of Screening for Prostate Cancer (ERSPC), yielding “somewhat different and more precise” estimates of screening’s effects on mortality, Dahm explained. 

The strongest evidence came from the ERSPC, which the investigators considered to have the lowest risk of bias among the available trials. Though screening frequency varied by trial, men in the ERSPC received screening every 2-4 years.

In sensitivity analyses based mostly on the ERSPC, PSA screening was associated with a 13% relative reduction in prostate cancer mortality (rate ratio [RR], 0.87; 95% CI, 0.80-0.95; moderate-certainty evidence). This translated to 2 fewer prostate cancer deaths per 1000 men screened over 23 years — 16 prostate cancer deaths per 1000 without screening and 14 per 1000 with screening. However, screening did not clearly reduce deaths from all causes (RR, 1.00; 95% CI, 0.98-1.02).

The review also found that PSA screening probably increased prostate cancer diagnoses by around 30%, mostly early-stage disease. In the ERSPC-based analysis, screening resulted in 36 additional prostate cancer diagnoses and 34 additional localized cancer diagnoses per 1000 men screened.

“That means that we detect many low-risk cancers that ultimately would have never had caused any problems, and those men who received the diagnosis may receive treatment and suffer side effects of those treatments,” Franco said.

In the ERSPC-based analysis, PSA screening also led to fewer metastatic cancers — about 5 fewer cancers per 1000 screened (RR, 0.65) — suggesting that screening may shift diagnoses away from metastatic presentation.

Overall, these findings suggest that the decision to undergo PSA screening is not a simple one, noted Matthew Hobbs, director of research at Prostate Cancer UK, who provided commentary in a Science Media Centre expert roundup. “We must be honest with men about the benefits but also about the potential harms,” he said.

Franco agreed that communicating the risks and benefits of PSA screening with patients is key. “It’s important to have discussions with patients and engage in shared decision-making to understand whether this test is right and acceptable,” he said during the briefing.

Welch agreed. “To be clear: PSA screening involves value judgments,” he explained. “Informed patients have to consider the trade-off: the frequent near-term harms vs the rare possibility of future benefit.” 

And there’s no single right answer, he said. “My choice reflects the value I place on avoiding both overdiagnosis and the medicalization that accompanies screening,” Welch said. 

The study had no commercial funding. Disclosures for the study authors are available with the original publication. Welch has received royalties from three books, including Should I Be Tested for Cancer? Hobbs reports work helping design and fund the TRANSFORM trial, a landmark prostate cancer screening trial.