Initial-to-nadir Prostate-specific Antigen Ratio Predicts Response to First-line Enzalutamide in Metastatic Castration-resistant Prostate Cancer.

Background/aim: No practical biomarkers predict the response to enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). The present study aimed to evaluate the prognostic value of the initial-to-nadir prostate-specific antigen (PSA) ratio (I/N PSA) in primary hormone therapy for metastatic hormone-naïve prostate cancer associated with the response to first-line enzalutamide in mCRPC.

Patients And Methods: Twenty-eight patients with mCRPC received first-line enzalutamide to determine the associations between I/N PSA in combined androgen blockade and clinical outcomes. The PSA response was defined as ≥90% decline from baseline in patients with mCRPC.

Results: The optimal cutoff I/N PSA value for PSA response was 1,219 (sensitivity=71.4%, specificity=92.9%, area under the receiver operating characteristic curve=0.85). The PSA response was 90.9% in the high I/N PSA group and 23.5% in the low I/N PSA group. The median overall survival, prostate cancer-specific survival, and radiographic progression-free survival after initiation of enzalutamide were statistically greater for the high I/N PSA group than the low group. Multivariable analysis showed that I/N PSA was an independent predictor of overall survival (hazard ratio=0.23; p=0.026).

Conclusion: In chemotherapy-naïve patients with mCRPC, I/N PSA was a predictive and prognostic biomarker for first-line enzalutamide. The I/N PSA can enable optimization of individual treatment in real-world clinical practice.