Prognostic Index Model for Progression-Free Survival in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Plus Prednisone

Prognostic models are needed to address the wide spectrum of clinical conditions in chemotherapy-naïve mCRPC. We developed a model that categorized patients with mCRPC treated with abiraterone acetate plus prednisone into 3 risk groups, and showed a threefold difference in progression-free survival between good versus poor risk group. With validation, this model may help guide treatment and clinical trial design. Background: Radiographic progression-free survival (rPFS) is associated with overall survival (OS) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Using readily assessable baseline clinical and laboratory parameters, we developed a prognostic index model for rPFS in chemotherapy-naïve mCRPC patients without visceral disease who were treated with abiraterone acetate plus prednisone. Methods: Data from the abiraterone acetate plus prednisone arm of COU-AA-302 were used. rPFS was defined based on modified Prostate Cancer Working Group 2 criteria. Baseline variables were assessed for association with rPFS through univariate Cox modeling. The lower (LLN) and upper (ULN) limits of laboratory normal were used to dichotomize most laboratory parameters; baseline median was used to dichotomize prostate-specific antigen (PSA). Prognostic factors for rPFS were identified by multivariate Cox modeling. Model accuracy was estimated by the C-index. Results: Presence of lymph node metastasis (hazard ratio [HR] = 1.76, P <.0001), lactate dehydrogenase > ULN (234 IU/L) (HR = 1.71, P =.0001), ≥ 10 bone metastases (HR = 1.71, P =.0015), hemoglobin ≤ LLN (12.7 g/dL) (HR = 1.47, P =.0030) and PSA > 39.5 ng/mL (HR = 1.42, P =.0078) were associated with poor outcome. Patients were categorized into 3 prognostic groups (good, n = 230; intermediate, n = 152; poor, n = 164) based on number of risk factors. Median rPFS was calculated (27.6, 16.6, and 8.3 months for good, intermediate, and poor, respectively). The C-index was 0.83 (95% confidence interval = 0.73-0.91). Conclusions: The prognostic index model for rPFS reveals differential outcomes based on factors readily available in clinical practice. If validated, this model can be integrated into clinical practice and design of risk-stratified trials.