Impact of PSA nadir on outcomes in metastatic hormone sensitive prostate cancer. An individual patient data meta-analysis

Introduction Prostate cancer represents the third leading cause of cancer-related mortality in the male population. Androgen deprivation therapy efficacy has been significantly enhanced by the addition of Docetaxel chemotherapy and androgen receptor pathway inhibitors (ARPI), such as Abiraterone, Enzalutamide, Apalutamide and Darolutamide. These agents have demonstrated improvements in both overall survival (OS) and progression-free survival (PFS). Nevertheless, a subset of patients eventually progresses to metastatic castration-resistant prostate cancer (mCRPC). The prostate-specific antigen (PSA) nadir, defined as the lowest PSA level achieved during therapy, has emerged as an early surrogate marker of treatment response and favorable prognosis. We conduct a meta-analysis to elucidate the prognostic value of the depth of PSA response in patients with metastatic mHSPC treated with ARPI or docetaxel. Methods This is an individual patient data (IPD) meta-analysis, in which were included prospective and retrospective clinical trials concerning mHSPC patients which received first line therapy with an ARPI or Docetaxel. Prospective or retrospective studies on mHSPC patients with available data on the lowest value of PSA reached were included. IPD from the Kaplan-Meier curves of enrolled studies were obtained with the software IPDfromKM. Primary endpoints of the analysis were overall survival (OS) and progression free survival (PFS) in patients who reached a PSA nadir ≤ 0.2 versus PSA nadir > 0.2. Results 8 reports from 8 studies were included, collecting data from 1638 patients for the OS analysis and 1104 for the PFS analysis. In terms of median PFS (mPFS), the PSA nadir ≤ 0.2 arm had an advantage: mPFS Not reached (NR) vs 12.1 months HR 0.19 (95% CI 0.16–0.23, p < 0.0001). In terms of median OS (mOS) the PSA nadir ≤ 0.2 arm had an advantage compared to the PSA nadir > 0.2: mOS 92.8 months vs 34 months (HR 0.27, 95% CI 0.22–0.33, p < 0.0001). Conclusions This meta-analysis confirms the prognostic value of PSA nadir in patients with mHSPC treated with docetaxel or ARPIs. Achieving a PSA nadir ≤ 0.2 ng/mL was significantly associated with improved OS and PFS, highlighting its relevance as an early marker of treatment efficacy.