Prognostic Nutritional Index and a Blood-Based Prognostic Tool in Prostate Cancer Treated with Abiraterone, Enzalutamide or Cabazitaxel

<i>Background and Objectives</i>: The prognostic nutritional index (PNI), a marker reflecting both nutritional and immune status, has been associated with prognosis in various malignancies. However, evidence in metastatic castration-resistant prostate cancer (mCRPC), particularly from non-Asian populations, remains limited. This study aimed to evaluate the prognostic value of baseline PNI and to develop a blood-based prognostic model in mCRPC patients treated with abiraterone acetate (AA), enzalutamide (ENZA), or cabazitaxel (CABA). <i>Materials and Methods</i>: This retrospective study included mCRPC patients treated with AA, ENZA, or CABA before or after docetaxel. PNI was calculated as: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³). Patients were classified into low-PNI (≤40.8) and high-PNI (>40.8) groups using the median PNI value. Survival outcomes were analyzed using Kaplan-Meier and Cox regression methods. <i>Results</i>: A total of 299 patients were analyzed: 133 (44.5%) received AA, 106 (35.5%) ENZA, and 60 (20.0%) CABA. Patients with high PNI had significantly longer median overall survival (OS; 30.2 vs. 12.6 months, <i>p</i> < 0.001), radiologic progression-free survival (rPFS; 13.5 vs. 6.7 months, <i>p</i> < 0.001), and PSA progression-free survival (PSA-PFS; 10.2 vs. 5.1 months, <i>p</i> < 0.001). These associations remained significant across all treatment subgroups. In multivariate analysis, prostate surgery (HR: 0.6), high PNI (HR: 0.5), PSA response (HR: 0.5), and elevated ALP (HR: 1.6) were independent predictors of OS. A prognostic model incorporating PNI, alkaline phosphatase, and anemia stratified patients into four risk groups with distinct OS: 49.1, 30.8, 18.8, and 9.1 months, respectively. <i>Conclusions</i>: This is the largest study to date in a non-Asian mCRPC population showing that baseline PNI is a strong, independent prognostic factor for survival. The proposed blood-based tool may aid in clinical risk stratification, pending prospective validation.