Reassessing the Role of Low PSA in Prognosis Across Grades of Prostate Cancer: A Cohort Study.

Background: Prior studies have concentrated exclusively on how different prostate-specific antigen (PSA) levels affect the prognosis of high-grade prostate cancer (PCa), often overlooking the prognosis of low-grade PCa.

Methods: The present cohort study included individuals diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. The all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) for each treatment group was calculated stratified by the four PSA levels (≤ 4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL). Fine and Gray competing-risks analyses were conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Cox proportional hazards regression analyses using PSA as a continuous variable with restricted cubic splines (RCS) were conducted to allow for potential nonlinear relationships.

Results: This study encompassed 416,825 male patients diagnosed with PCa. Compared to individuals with PSA value between 4.1 and 10.0 ng/mL, a significant association between low levels of PSA (≤ 4.0 ng/mL) and an increased risk of ACM (AHR = 1.15, 95% CI: 1.12-1.19; p < 0.001) and PCSM (AHR = 1.49, 95% CI: 1.38-1.61; p < 0.001) was observed. Additionally, the increased risk of ACM (AHR = 1.35, 95% CI: 1.29-1.40; p < 0.001) and PCSM (AHR = 1.84, 95% CI: 1.67-2.02; p < 0.001) are more pronounced within the first 5 years post-diagnosis. In most subgroups, similar results were observed. The RCS curves further corroborated the correlation between PSA value and the risk of mortality.

Conclusion: Low PSA levels are notably linked to a heightened risk for both ACM and PCSM, irrespective of the grade of PCa being high or low. There is a need to initiate new studies that tackle novel diagnostics and therapeutics.