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.
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.
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).
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.
This study looked at medical records from patients who received androgen deprivation therapy with or without other treatments (2018–2023) for metastatic castration‐sensitive prostate cancer. Prostate‐specific antigen (PSA) typically drops after treatment, which indicates that the treatment is working. Patients whose PSA levels dropped below 0.2 ng/mL within 9 months of starting treatment were less likely to die than patients who did not, whether their PSA levels also decreased by at least 90% or not. These findings suggest that reaching a PSA level of less than 0.2 ng/mL after starting prostate cancer treatment can maximize the chance of survival.
Cancer. 2026 Aug 15 [Epub]
Stephen J Freedland, Wei Gao, Maëlys Touya, Hongbo Yang, David Russell, Jingyi Chen, Grace Chen, Jasmina I Ivanova
Department of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA., Analysis Group Inc., Boston, Massachusetts, USA., Astellas Pharma Global Development, Northbrook, Illinois, USA., Pfizer Inc., New York, New York, USA.