Ability of C-reactive protein to complement multiple prognostic classifiers in men with metastatic castration resistant prostate cancer receiving docetaxel-based chemotherapy

OBJECTIVE Given the recent emergence of C-reactive protein levels as a novel prognostic factor in men with metastatic castration-resistant prostate cancer (mCRPC), we sought to evaluate the independent prognostic ability of C-reactive protein in the context of published prognostic nomograms, risk grouping and disease state models in men receiving docetaxel-based chemotherapy for mCRPC. PATIENTS AND METHODS A large randomized phase II trial (CS-205) of mCRPC patients who received docetaxel-prednisone + AT-101 (Bcl-2 inhibitor) or docetaxel-prednisone + placebo was analyzed retrospectively (n = 220). Overall survival (OS), progression-free survival (PFS) and measures of discriminatory ability were assessed in a hypothesis-generating analysis using Cox regression and concordance probabilities. Patients from both treatment groups were combined for this analysis because no significant differences in outcomes were observed. Because some factors used in nomograms were not collected or defined differently, risk was estimated based on slightly modified versions of nomograms. RESULTS C-reactive protein was independently prognostic for OS and PFS (P <= 0.002) after adjusting for all modeled risk estimates and classifiers. C-reactive protein showed a concordance probability of 0.65 for both OS and PFS. A 10-factor modified prognostic model based on the TAX327 trial had the greatest observed discrimination ability for OS and PFS (concordance probability = 0.623 and 0.603, respectively) among the modified nomograms or classifiers. Adding the TAX327 model risk estimates to C-reactive protein did not substantially increase discrimination ability over C-reactive protein alone. CONCLUSIONS Current prognostic classifications provide modest discrimination of outcomes in mCRPC receiving docetaxel-based chemotherapy, highlighting the need for improved risk-based models. Baseline C-reactive protein appears to be an useful, independent prognostic factor and prospective external validation is warranted.