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Keywords:

  • C-reactive protein;
  • docetaxel;
  • metastatic castration resistant prostate cancer;
  • nomogram;
  • PCWG-2 clinical subtypes;
  • risk groups

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.