Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms

Abstract

Background: Median overall survival (OS) in men with metastatic castration-resistant prostate cancer (CRPC) was 13-16 mo in the predocetaxel era. Prognostic nomograms for survival estimation in CRPC were constructed prior to the introduction of docetaxel and other novel treatments.

Objective: To examine whether prognostic models still accurately reflect survival in a large cohort of trial participants.

Design, setting, and participants: Survival analysis of 442 men with CRPC sequentially treated in clinical trials at our institution from June 2003 to December 2011.

Outcome measures and statistical analysis: Predicted survival by Halabi and Smaletz nomograms was compared to observed survival. Cox model multivariate analysis (MVA) used variables at referral, including performance status (PS); levels of prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), haemoglobin (Hb), and albumin; presence of visceral disease, and metastatic disease at diagnosis.

Results and limitations: From point of referral, chemotherapy-naïve patients had a median OS of 30.6 mo (95% confidence interval [CI], 27.6-36.5 mo). In contrast, predicted survival using the Halabi and Smaletz models was 21 and 18 mo, respectively. In these patients, poor PS, lower Hb level, and increasing LDH level were the strongest predictors in the MVA. In patients referred after chemotherapy, survival from referral was 17.5 mo (95% CI, 16.0-19.5 mo) and increasing LDH level and presence of visceral metastases were the strongest predictors of survival. Median OS from diagnosis of CRPC was 40.7 mo in the overall cohort (95% CI, 36.8-44.0 mo). Clinical trial participation was safe, with low mortality rate. This cohort of men participated in phase 1, 2 and 3 trials and expanded access programs; their data may not reflect survival in all CRPC patients.

Conclusions: Due to the impact of highly effective novel therapies on survival, prognostic nomograms in current use require revalidation regarding their ability to predict survival in CRPC.

Keywords: Castration-resistant prostate cancer; Prognostic factors; Prognostic nomogram; Survival.