• BJU international · Dec 2012

    Randomized Controlled Trial Multicenter Study Comparative Study

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

    • Gregory R Pond, Andrew J Armstrong, Brian A Wood, Lance Leopold, Matthew D Galsky, and Guru Sonpavde.
    • Department of Oncology, McMaster University and Ontario Clinical Oncology Group, Hamilton, Ontario, Canada.
    • BJU Int. 2012 Dec 1;110(11 Pt B):E461-8.

    UnlabelledWhat's known on the subject? and What does the study add? Serum C-reactive protein (C-reactive protein) is emerging as a potential novel prognostic factor in metastatic castration-resistant prostate cancer (mCRPC). In the present study, a prospective trial was investigated retrospectively and a significant prognostic impact for C-reactive protein that was independent of multiple published prognostic models was identified in men receiving docetaxel-based chemotherapy for mCRPC. Prospective validation is warranted.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.© 2012 BJU INTERNATIONAL.

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