Reducing Harms Associated with PSA Screening

Kenny Lin, MD, MPH
Posted on April 15, 2024

In the U.K. Cluster Randomized Trial for PSA Testing for Prostate Cancer (CAP), more than 400,000 men seen in primary care practices between 2001 and 2009 were either invited to receive a single prostate specific antigen (PSA) screening test or usual care. After a median follow-up of 10 years, there were more prostate cancer diagnoses in the screening group, but no effect was seen on prostate cancer mortality. (Men diagnosed with localized prostate cancer were invited to participate in a separate trial comparing active monitoring, surgery, and radiotherapy, which Dr. Middleton discussed previously on the AFP Community Blog.) In a secondary analysis of the CAP trial after five more years of follow-up, researchers found a small difference in prostate cancer mortality favoring the screening group (absolute reduction = 0.09%; number needed to screen = 1,111 to prevent one prostate cancer death). However, the screening group was at greater risk of detection of low-grade (Gleason score ≤ 6) cancers that are likely to be clinically insignificant and represent overdiagnosis.

Magnetic resonance imaging (MRI) is increasingly being used as a triage strategy for men with suspected prostate cancer to avoid unnecessary biopsies while still detecting clinically significant cancers at curable stages. A 2024 systematic review and meta-analysis of 72 studies (n = 36,366) examined associations between MRI Prostate Imaging Reporting & Data System (PI-RADS) findings, clinical data, and clinically significant prostate cancer. Compared with performing prostate biopsies on all patients, avoiding biopsies in patients with PI-RADS category 3 or fewer lesions and PSA density of 0.10 or less reduced unnecessary biopsies by 30% and missed 1 in 17 significant tumors. Increasing the PSA density threshold to 0.15 reduced unnecessary biopsies by 48% and missed 1 in 15 significant tumors.

Several randomized trials are evaluating the effectiveness of a screening strategy combining MRI and a PSA-based biomarker risk score (e.g., 4-Kallikrein Panel) to determine which patients with abnormal PSA levels should be biopsied. The ProScreen trial, involving more than 60,000 Finnish men 50 to 63 years of age, recently reported preliminary results from its baseline screening round. Researchers found that compared with the usual care group, men invited for screening were more likely to have high-grade prostate cancer detected (1 per 196 men) at the cost of also being more likely to have low-grade prostate cancer detected (1 per 909 men). Whether these small differences will lead to meaningful improvements in prostate cancer mortality will not be known for at least several years.

A systematic review published last week in JAMA reiterated the importance of continuing to use cancer-specific mortality as the primary outcome in randomized trials of cancer screening. The authors evaluated the strength of correlations between reductions in stages 3 and 4 cancer (a proposed surrogate outcome for trials of multicancer screening tests) and reductions in cancer-specific mortality in 41 published randomized trials of screening for breast, colorectal, lung, ovarian, prostate, and other cancers. They found high correlations for ovarian and lung cancers, only a moderate correlation for breast cancer, and weak correlations for colorectal and prostate cancers.