How low do you need to go? Association between various prostate‐specific antigen response measures and clinical outcomes in metastatic castration‐sensitive prostate cancer in the Veterans Health Administration data

Abstract

BACKGROUND: Multiple phase 3 metastatic castration-sensitive prostate cancer (mCSPC) studies consistently show a prostate-specific antigen (PSA) 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. METHODS: This retrospective analysis of Veterans Health Administration data (2006-2024) assessed the association between PSA response and overall survival (OS) in patients with mCSPC who initiated androgen deprivation therapy (ADT) ± 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. RESULTS: 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 (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.40-0.54) versus patients who did not. OS improvements with a PSA of <0.2 ng/mL were similar, regardless of ≥90% (adjusted HR, 0.43; 95% CI, 0.35-0.52) or <90% PSA decline (adjusted HR, 0.36; 95% CI, 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 androgen receptor pathway inhibitors versus ADT alone were more likely to achieve a PSA of <0.2 ng/mL during PSA follow-up (adjusted HR, 1.71; 95% CI, 1.55-1.88). CONCLUSIONS: In a real-world mCSPC setting, achieving a PSA of <0.2 ng/mL (whether or not a PSA decline of 90% was reached) within 9 months of initiating ADT ± other treatments was associated with improved OS, which supports a PSA nadir of <0.2 ng/mL for optimizing mCSPC outcomes.