Task Force Changes Stance on Value of PSA Test

In a departure from earlier guidance, the US Preventive Services Task Force (USPSTF) has concluded that there is a small mortality benefit associated with prostate-specific antigen (PSA)-based prostate cancer screening for men aged 55 to 69 years,¹ “justifying the offer of PSA testing selectively to men in this age group based on the judgment of the physician and the values of the patient.”

The USPSTF decision changes a 2012 recommendation that discouraged the use of routine PSA screening for men of all ages and concluded that there was “moderate certainty” that the benefits of asymptomatic screening did not outweigh the harms (Table). That decision was based in part on high rates of negative prostate cancer biopsies and a tendency to overtreat low-grade prostate cancer.

Table. USPSTF Updated Guidelines on PSA Testing

Whereas previously the USPSTF was concerned about a lack of evidence from high-grade trials about the merits of PSA screening, the latest recommendation is based on what the task force considers more reliable information. “Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened,” according to the recommendation published in JAMA.¹“The potential benefits and harms of screening for prostate cancer are closely balanced” in this age cohort, the authors stated. The task force gave the recommendation a C grade, meaning that there is moderate certainty that PSA screening produces a small net benefit in this patient population.

PSA testing was approved in 1995 by the FDA for early detection, but PSA levels do not correlate specifically to the existence of prostate cancer or to more aggressive forms of the disease. Also, new evidence indicates that prostate cancer is increasingly managed with active surveillance, which involves deferring treatment unless disease progression is detected during periodic physical examination. “Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties,” Fenton et al wrote in a USPSTF evidence report.²

Whereas in 2008 the task force concluded there was insufficient evidence to make a recommendation on PSA screening for prostate cancer in men under the age of 70, it recommended against use of the test for men aged 75 and older. In the fresh guidance, the USPSTF recommends against routine testing for men aged 70 years or older.

"Fair Quality" Evidence

In reassessing the guidelines, reviewers sought to determine, among other issues, whether clear evidence exists that PSA screening reduces short- or long-term prostate cancer morbidity and mortality. They also sought to determine the harms of screening for prostate cancer and diagnostic follow-up. Their search for evidence led to a review of 303 full-text articles, a total that was augmented by 17 new articles since 2011.The task force included data from the European Randomized Study of Screening for Prostate Cancer (ERSPC); the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial; and the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), among others. Those trials, deemed “fair quality,” evaluated the PSA screening outcomes by prostate cancer morbidity, mortality, and all-cause mortality. The authors also included data from extended follow-up results in the ERSPC30 and PLCO29 trials.

Median follow-up was 13 years in the PLCO and ERSCP trials and 10 years in the CAP trial. In PLCO, cumulative incidence of prostate cancer in the screening and control groups was 11.1% and 9.9%, respectively (relative risk [RR], 1.12; 95% CI, 1.07-1.17); ERSPC, 10.2% and 6.0% (RR, 1.57; 95% CI, 1.51-1.62); and CAP, 4.3% and 3.6% (RR, 1.19; 95% CI, 1.14-1.25).

In PLCO, at a median follow-up of 14.8 years, the prostate-cancer— specific mortality rate was 4.8 per 10,000- person years for men in the screening group compared with 4.6 per 10,000 in the control group (RR, 1.04; 95% CI, 0.87-1.24). In CAP, at a median follow-up of 13 years, the prostate-cancer–specific mortality rate was 3.0 versus 3.1 per 10,000 person-years between screened patients and controls (RR, 0.96; 95% CI, 0.85-1.08). In ERSPC, at a median of 13 years of follow-up, the rate was 4.3 versus 5.4 per 10,000 years, respectively (RR, 0.79; 95% CI, 0.69-0.91).

“In the ERSPC trial, the absolute risk reduction in prostate cancer mortality associated with screening was 1.1 deaths per 10,000 personyears (95% CI, 0.5-1.8), or 1.3 fewer prostate cancer deaths per 1000 men,” Fenton et al wrote. “The number needed to invite [to screening] to prevent 1 prostate cancer death was 781 (95% CI, 490-1929), and the number needed to diagnose [the existence of disease] was 27 (95% CI, 17-66).”

Among men aged 65 to 74 years at baseline in PLCO or men aged 70 to 74 years at baseline in the ERSPC, screening was not associated with statistically significant reductions in disease-specific cancer mortality. At a median follow-up of 10 to 14.8 years, screening was not associated with a statistically significant reduction in all-cause mortality in any of the 3 trials.

Reviewers also sought to determine whether evidence indicated use of a prebiopsy prostate cancer risk calculator in combination with PSA screening accurately identifies men with clinically significant prostate cancer compared with PSA screening alone.

Both calculators were better than PSA screening alone at distinguishing between men who had clinically significant prostate cancer and those who did not. However, in several cohorts, the calculators underestimated or overestimated the actual risk.

“Prebiopsy risk calculators can discriminate between men with and without high-risk cancer better than PSA screening alone, but net clinical benefit of routine calculator use in biopsy decisions is not established by existing evidence,” the authors wrote.

In an accompanying editorial, H. Ballentine Carter, MD, director of the Prostate Cancer Program at Johns Hopkins School of Medicine, in Baltimore, Maryland, wrote that physicians should not screen patients with multiple comorbidities or older men, who are not likely to gain life-years from treatment.³

Active surveillance is preferred over surgery or radiotherapy for men with favorable-risk disease,” Carter added, and PSA screening every 2 to 4 years, rather than annually, could reduce false-positive test results and overdiagnosis.

References

1. Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(18):1901-1913. doi: 10.1001/jama.2018.3710.
2. Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Melnikow J. Prostate-specific antigen—based screening for prostate cancer evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;319(18):1914-1931. doi: 10.1001/jama.2018.3712.
3. Carter HB. Prostate-specific antigen (PSA) screening for prostate cancer: revisiting the evidence. JAMA. 2018;319(18):1866-1868. doi: 10.1001/jama.2018.4914.