PSA screening reduces prostate cancer mortality over 15 years, Finds new randomized clinical trial

The secondary analysis of a randomized clinical trial (CAP) comprising 415 357 men aged 50 to 69 found that a single invitation for a PSA screening test reduced prostate cancer mortality at a median follow-up of 15 years, however, the absolute mortality benefit was small, compared with no invitation for routine PSA testing.

"The risk of death from prostate cancer was lower in the group invited to screening (0.69% vs 0.78%; mean difference, 0.09%) versus the control group," the researchers reported.

Prostate cancer remains one of the most prevalent forms of cancer among men globally, with mortality rates continuing to pose a significant concern. In light of this, the findings from the CAP trial hold immense significance in the realm of cancer research and public health.

The CAP trial reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), however, there is no clarity on the long-term effects of PSA screening on prostate cancer mortality. Therefore, Richard M. Martin, University of Bristol, Bristol, United Kingdom, and colleagues aimed to evaluate the effect of a single PSA screening on prostate cancer-specific mortality at a median 15-year follow-up versus no invitation for screening.

The secondary analysis included men aged 50 to 69 years, identified at 573 primary care practices in England and Wales. Primary care practices were randomized between 2001 and 2007, and enrollment was done between 2002 to 2009.

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or greater. The control group received standard practice (no invitation).

The primary outcome was previously reported. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The four remaining were all-cause mortality, prostate cancer-specific mortality, and prostate cancer stage and Gleason grade at diagnosis.

Of 415 357 eligible men (mean age, 59.0 years), the analyses included 98% of men. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08%, and 6.94%, respectively).

The study led to the following findings:

• At a median 15-year follow-up, 1199 men in the intervention group (0.69%) and 1451 men in the control group (0.78%) died of prostate cancer (rate ratio [RR], 0.92).
• Compared with the control, the PSA screening intervention increased the detection of low-grade (Gleason score [GS] ≤6: 2.2% versus 1.6%) and localized (T1/T2: 3.6% versus 3.1%) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors.
• There were 45 084 all-cause deaths in the intervention group (23.2%) and 50,336 deaths in the control group (23.3%) (RR, 0.97).
• Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

"In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening versus the standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, there was a small absolute reduction in deaths," the researchers wrote.

In conclusion, CAP Randomized Clinical Trial findings offer hope in the fight against prostate cancer, reaffirming the critical role of PSA screening in saving lives. Moving forward, continued efforts to enhance screening protocols and promote informed decision-making will be pivotal in advancing prostate cancer care and reducing mortality rates worldwide.

Reference:

Martin RM, Turner EL, Young GJ, et al. Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial. JAMA. 2024;331(17):1460–1470. doi:10.1001/jama.2024.4011