Chromogranin A and neurone‐specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration‐resistant prostate cancer undergoing abiraterone therapy

Abstract

ObjectiveTo determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post-chemotherapy setting. Patients and MethodChromogranin A (CGa) and neurone-specific enolase (NSE) were determined in serum drawn before treatment with abiraterone from 45 patients with mCRPC. Outcome measures were overall survival (OS), prostate-specific antigen (PSA) response defined by a PSA level decline of ≥50%, PSA progression-free survival (PSA-PFS), and clinical or radiographic PFS. ResultsThe CGa and NSE serum levels did not correlate (P = 0.6). Patients were stratified in to low-(nine patients), intermediate- (18) or high-risk (18) groups according to elevation of none, one, or both neuroendocrine markers, respectively. The risk groups correlated with decreasing median OS (median OS not reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA-PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression analysis the combination of CGa and NSE (≥1 marker positive vs both markers negative) remained significant predictors of OS, clinical or radiographic PFS, and PSA-PFS. We did not observe a correlation with PSA response (63% vs 35% vs 31%; P = 0.2). ConclusionChromogranin A and NSE did not predict PSA response in patients with mCRPC treated with abiraterone. However, we observed a correlation with shorter PSA-PFS, clinical or radiographic PFS, and OS. This might be due to an elevated risk of developing resistance under abiraterone treatment related to neuroendocrine differentiation.

Cell-Free DNA and Neuromediators in Detecting Aggressive Variant Prostate Cancer

“…In the literature, a predominance of arbitrary thresholds of neuromediators was chosen after 1-time analysis before therapy to correlate them with outcome. Recently, 2 published trials analyzed CGA before AA therapy and found predictive and prognostic significance [18,19]. Despite the limitations, CGA was shown to be a significant predictive biomarker.…”

Serum Neuroendocrine Markers Predict Therapy Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis

“…Three hundred and fifty-three papers were identified through joint search keywords and their free-text words from 3 electronic databases and from these papers, 146 articles were excluded by removing of duplicates and 194 were precluded based on titles and abstracts. Finally, 6 of remaining 13 trials met the inclusion criteria and were selected for this meta-analysis [24][25][26][27][28][29].…”

“…As with the characteristics reflected by Table 1, all included studies were hospital-based retrospective validation studies, of which 3 were cohort studies [24][25][26] and 3 were case-control studies [27][28][29]. All publications were published from 2010 through 2017.…”

“…All publications were published from 2010 through 2017. A total of 234 participants were included in the analysis, 168 of whom received novel hormonal therapy (chemotherapy pretreated or chemotherapy-naïve) such as AA [24,25,28] or ENZ [27] (range of sample sizes = 35-48); the remaining patients only received chemotherapy as drugs docetaxel [26,29]. The mean age of participants was 71.3 years across all studies.…”

“…The results of the methodologic quality assessment of the studies [24][25][26][27][28][29] are presented shown in Table 2. These experiments were launched by different multi-center regions, so that the external validity is good overall.…”