One-time screening with a prostate-specific antigen (PSA) test failed to reduce prostate cancer deaths at 10 years, despite an uptick in diagnoses of the disease, according to results of a randomized trial that included over 400,000 British men.
During the trial, 549 of 189,386 patients in the screening arm died from prostate cancer (0.30 per 1,000 person-years) compared with 647 of 219,439 patients in the control arm (0.31 per 1,000 person-years) for a rate ratio of 0.96 (P=0.50).
“The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) was designed to determine the effects of a low-intensity, single invitation PSA test,” wrote Richard M. Martin, PhD, of the University of Bristol, England, in JAMA. “Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening.”
The trial included 419,582 men ages 50 to 69 screened at 573 primary care practices across the United Kingdom. Patients were recruited beginning in 2001, with follow-up concluding in 2016.
While no reduction in deaths due to prostate cancer were seen among screened patients, more cases of the disease were diagnosed in men receiving a PSA test (4.3%) compared with unscreened patients (3.6%). More tumors with a Gleason score of 6 or lower were identified in the screened group compared with the control group (1.7% versus 1.1%, respectively).
Localized disease (stage T1 or T2 cancer) was diagnosed at a more frequent rate in the screened group (2.6% versus 1.9% in the control group); in turn, fewer cases of advanced-stage cancer were diagnosed in this group (0.5% versus 0.6% in the control group).
Of the 549 men who died of prostate cancer in the screening group, only 188 had visited the clinic for PSA testing. Lethal cancer was diagnosed in 59 of these 188. Of the remaining 129 patients:
- 68 were ineligible for prostate biopsy due to a PSA level less than 3.0 ng/mL,
- 42 did not undergo PSA testing despite having attended the clinic,
- 15 men had a PSA level 3.0 ng/mL or higher yet did not undergo a biopsy,
- and 4 men had a benign biopsy.
In the all-cause mortality analysis, 25,459 died in the intervention group compared with 28,306 in the control group for a RR of 0.99 (P=0.49).
Screening for prostate cancer using PSA tests remains controversial, as the potential benefits of disease detection in its early stages can be outweighed by harms from overtreatment. In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against routine PSA screening for men of any age, but in 2017 adjusted this recommendation and now support an individualized approach to screening for men ages 55 to 69.
“It has been hypothesized that screening men in their early 50s may be more effective than at a later age,” the authors wrote. “However, we did not find statistical evidence to support this.”
In terms of adherence to screening, 75,707 patients (40%) of the 189,386 men assigned to the intervention arm attended the clinic for PSA testing; 67,313 of these men underwent PSA testing. High PSA levels — 3.0 ng/mL to 19.9 ng/mL — were detected in 6,857 patients and 5,850 underwent a biopsy.
In an editorial accompanying the article, Michael J. Barry, MD, of Harvard Medical School and Massachusetts General Hospital in Boston, wrote: “A key question is whether the findings from the CAP trial should swing the pendulum further in the direction of not offering screening PSA tests. Based on the CAP results, an offer of a single PSA screen in a population of men aged 50 to 69 years is ineffective, and given the higher risk of a prostate cancer diagnosis this approach engenders, likely does more harm than good.”
Barry, who is a member of the USPSTF, added that while further follow-up from CAP could potentially reveal benefit, based on the evidence so far “that eventuality seems unlikely.”
Martin and co-authors reported no conflicts of interest. Barry is chief science officer at Healthwise, and grants from the company have been awarded to Massachusetts General Hospital.
The CAP trial was funded by grants from Cancer Research U.K., and partial funding was provided by the U.K. Department of Health, National Institute of Health Research.