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

ABSTRACT 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.