Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer

BackgroundTo determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). MethodsWe conducted an analysis in 115 chemotherapy-naive mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED. ResultsSerum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P=0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P<0.001, and 14.23 vs 10.30 months, P=0.02) and rPFS, respectively (18.33 vs 11.37 months, P<0.001, and 17.10 vs 12.07 months, P=0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED. ConclusionsWe hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.