Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer

Abstract

Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.

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

“…These results have further proved that AA might not significantly lead to progression of NED in mCRPC in general. Furthermore, our present results are supported by a previous report . von Hardenberg et al, conducted an analysis in 35 chemotherapy‐naive CRPC patients at five institutions.…”

“…Experimental finding has supported the view that the anti‐androgen enzalutamide can promote NED . Previous research has claimed that CRPC patients after first‐line treatment with AA are not at a higher risk for developing NED . However, it was an one‐time analysis which was lack of a comparison of marker analysis before and after treatment with AA.…”

“…It has been hypothesized that NED is caused by selective pressure under AR‐targeted therapy and might lead to adaptive treatment resistance . NED has been identified in around 43‐85% of cases in CRPC, which express NED markers such as chromogranin A (CgA) and neurone‐specific enolase (NSE) . In addition, elevation of NED markers in serum has shown to be in keeping with the rate of NED detected in tumor tissue .…”

Risk of development of visceral metastases subsequent to abiraterone vs placebo: An analysis of mode of radiographic progression in COU‐AA‐302

“…Almost all of these studies show an overall increase in expression of these resistance markers at progression. However, studies that focused on whether abiraterone was specifically associated with increased expression of some of these neuroendocrine markers, in particular, have not identified an association specifically with abiraterone . Another study looking at lifetime risk of development of visceral metastases did not identify an association with prior treatment with abiraterone or enzalutamide with the development of visceral metastases .…”

Circulating biomarkers of neuroendocrine prostate cancer: an unmet challenge

“…Although CGA and NSE did not predict PSA response, they correlated with clinical and radiographic progression‐free survival (PFS), as well as overall survival (OS). The association between these biomarkers and clinical outcomes in metastatic CRPC has been confirmed in retrospective studies . According to the authors, this association, independently of PSA response, underlines the sub‐clonality of this disease, and the key role of androgen receptor (AR) signalling, even in advanced disease .…”