Early favorable prostate-specific antigen response prediction in metastatic hormone sensitive prostate cancer

There is an unmet need for a tool that could predict early favorable prostate-specific antigen (PSA) response in metastatic hormone sensitive prostate cancer (mHSPC) patients receiving androgen receptor pathway inhibitor (ARPI). Here, we train and validate a multivariable logistic regression model to predict early favorable PSA response (≤0.2 ng/mL by 6 months) in these patients. Patients randomly allocated to the ARPI arms of the LATITUDE (abiraterone), TITAN (apalutamide), and ARASENS (darolutamide) trials, are split 60:40 into training (n = 1030) and internal validation (n = 688) cohorts. The locked model is validated in an independent external validation cohort - the enzalutamide arm of the ENZAMET trial (n = 540). The area under curve and Brier score for the locked model in the external validation cohort are 0.82 (95% confidence interval [CI] = 0.78–0.85) and 0.16, respectively. Stratification by predicted probability tertiles show PSA response rates of 92% (95% CI = 88–96), 74% (95% CI = 68–81), and 39% (95% CI = 32–47), respectively. Pending prospective validation, our model predicts early favorable PSA response supporting its potential role in guiding treatment decisions. There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.