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
Stephen J. Freedland, Wei Gao, Maëlys Touya, Hongbo Yang, David Russell, Jingyi Chen, Grace Chen, Jasmina I. IvanovaABSTRACT
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.