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

Authors


  • G.R. Pond and A. Armstrong contributed equally to this article.

Guru Sonpavde, 501 Medical Center Boulevard, Webster, TX 77598, USA. e-mail: guru.sonpavde@usoncology.com

Abstract

Study Type – Retrospective analysis of clinical trial

Level of Evidence 3

What'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.

Ancillary