PROSTATE-SPECIFIC antigen (PSA) testing remains a cornerstone in the early detection of prostate cancer, yet its interpretation is complicated by variability in results. Current guidelines recommend repeating a PSA test after an elevated reading before progressing to more invasive investigations, but the necessity of this step for all patients has been uncertain. A new analysis from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial provides valuable insight into this question.
The retrospective cohort study included 11,176 men aged between 54 and 75 years who underwent annual PSA screening for six years. Researchers focused on three biopsy thresholds, 2.5, 3.0, and 4.0 ng/mL, and assessed whether elevated PSA levels fell below these thresholds at the following yearly measurement. Findings showed that 22% of PSA results at or above 2.5 ng/mL dropped below this threshold within a year. Similar patterns were observed at the higher thresholds. At the patient level, more than half of men with at least one elevated PSA subsequently recorded a level below the same threshold.
A predictive scoring system, incorporating both current and prior PSA values, revealed that patients with persistently elevated levels had a very low likelihood, under 10%, of their PSA decreasing below the threshold at follow-up. This distinction is clinically important, suggesting that while most men benefit from repeat testing to confirm an initial elevation, those with a consistent pattern of raised PSA values could reasonably proceed directly to further diagnostic evaluation, including biopsy.
The study highlights the significant intra-individual variability of PSA and reinforces the role of confirmatory testing in preventing unnecessary procedures. At the same time, it supports a more tailored approach, where patients with persistent PSA elevation may avoid delays in diagnosis by moving promptly to further evaluation. These findings underline the importance of considering PSA history, rather than single results alone, when planning prostate cancer workup.
Reference
Pickersgill NA et al. Prostate-specific antigen levels among participants receiving annual testing. JAMA Oncol. 2025;DOI:10.1001/jamaoncol.2025.3386.
