Clinicopathological predictors of favourable response to docetaxel in patients with metastatic castration-resistant prostate cancer.

Abstract

Background: The onset of castration-resistance portends a poor prognosis with limited therapeutic options in men with advanced prostate cancer. Docetaxel improves overall survival in metastatic castrate-resistant prostate cancer (mCRPC). However, depth and durability of responses are heterogenous and it remains unclear which patients benefit most from this therapy. Our study therefore aimed to identify the clinical and pathological factors that predict a favourable response to docetaxel in men with mCRPC. Methods: Data from the prospective multi-site electronic Prostate Cancer Australian Database (ePAD) were extracted to identify favourable responders (FR) to docetaxel (defined as a time to treatment failure (TTF) of ≥ 12 months) and typical responders (TR) (TTF < 12 months). Variables were compared between FR and TR groups using descriptive statistics and association with overall survival (OS) was analysed using Cox proportional hazards multivariate modelling. Results: We identified 206 patients who received docetaxel for mCRPC. 140 (68%) were TRs and 66 (32%) were FRs. The FR group had longer median duration of therapy (5.6 vs 4.9 months, p=0.05) and time to PSA nadir (8.9 vs 3.9 months, p=0.002). They were more likely to have a >50% PSA response (PSA50) to therapy (64% vs 54%, p=0.02). There were no significant differences in median age, Gleason score, performance status, the presence of visceral or de novo metastatic disease. The FR group had superior OS on univariate analysis (HR 0.57, 95%CI 0.38-0.85, p=0.006). However on multivariate analysis, independent predictors of improved OS included time to CRPC >12 months (HR 0.44, 95%CI 0.27-0.59, p<0.001), PSA doubling time >3 months (0.49, 95%CI 0.29-0.84, p=0.009) and a PSA50 response (0.60, 95%CI 0.35-1.02, p=0.06). Conclusions: Our real-world study suggests that a longer treatment duration, time to PSA nadir and PSA50 response are important factors that predict favourable response to Docetaxel. Observed predictors of OS are consistent with existing literature. Given the changing treatment landscape, further evaluation of clinicopathologic predictors in the hormone sensitive setting is warranted.