Retrospective analysis of association between various PSA response measures and outcomes in mCSPC in the Veterans Health Administration data

Multiple phase 3 metastatic castration-sensitive prostate cancer (mCSPC) consistently show a PFS nadir of <0.2 ng/mL to be the preferred threshold for PSA response; however, in real-world practice, physicians often use other metrics such as percentage of PSA decline. A retrospective analysis of Veterans Health Administration data (2006-2024) assessed the association between PSA response and overall surviva (OS) in mCSPC patients who initiated androgen deprivation therapy (ADT) with or without other treatments, using landmark analyses with adjusted Cox regressions. PSA response metrics included ≥ 90% PSA decline and a PSA of <0.2 ng/mL within 9 months of starting therapy. Among 4890 patients, 44% reached a PSA of ≤0.2 ng/mL, and 74% had ≥90% PSA decline. Patients with a PSA of <0.2 ng/mL within 9 months of ADT initiation had a reduced risk of death after this time point versus patients who did not (HR 0.46; 95% CI 0.40-0.54). OS improvements with a PSA of <0.2 ng/mLwere similar regardless of ≥90% (aHR 0.43; 95% CI 0.35-0.52) or <90% PSA decline (0.36; 0.23-0.56). Achieving ≥90% PSA decline without a PSA of <0.2 ng/mL was unrelated to improved OS. Patients who initiated ADT plus ARPIs versus ADT alone were more likely to achieve a PSA of <0.2 ng/mL during PSA follow-up. The authors conclude that in a real-world mCSPC setting, achieving a PSA of <0.2 ng/mL within 9 months of initiating ADT with or without other treatments was associated with improved OS, whether or not a PSA decline of 90% was reached, which supports a PSA nadir of <0.2 ng/mL for optimizing mCSPC outcomes (graphical abstract).