Stage-specific prognostic value of PSA in prostate cancer: a multicentre KAMU-ON study

To evaluate whether the prognostic value of initial prostate-specific antigen (PSA) differs according to disease stage in patients with prostate cancer.

This multicentre retrospective cohort study used data from the Kaga Million Uro-Oncology Network (KAMU-ON) registry. Patients diagnosed between 1993 and 2024 with available data on overall survival, initial PSA, Grade Group, and disease stage were included. Disease stage was classified as localised, nonmetastatic advanced, or metastatic. Restricted cubic spline analyses and multivariable Cox proportional hazards models evaluated stage-specific associations between PSA and overall survival.

Among 7747 patients, 5578 had localised disease, 1223 had nonmetastatic advanced disease, and 946 had metastatic disease. The median follow-up was 58.0 months. PSA-survival associations differed significantly across disease stages (P for interaction = 0.0014). In localised disease, mortality risk increased progressively with higher PSA levels. In nonmetastatic advanced disease, the association was attenuated. In metastatic disease, a non-linear association was observed, with increased mortality risk at both lower and higher PSA levels. Patients with metastatic disease and PSA < 3.5 ng/mL had a higher estimated mortality risk than those with PSA 3.5-<10 ng/mL (adjusted HR 5.86, 95% CI 2.22-15.43), although this subgroup comprised only eight patients.

The prognostic value of initial PSA appeared to differ according to disease stage. These findings generate the hypothesis that low PSA may have different prognostic implications across disease stages. External validation is required, particularly for the very low-PSA metastatic subgroup.