Serum Chromogranin-A based Prognosis In Metastatic Castration Resistant Prostate Cancer

OBJECTIVE: To determine the prognostic value of serum chromogranin-A (CGA) in a two-cohort study of men with metastatic castrate resistant prostate cancer (mCRPC) and to compare with circulating tumor cells (CTCs) based prognosis. PATIENTS AND METHODS: A two cohort based evaluation for serum CGA for prognostication in CRPC stage was performed using a screening cohort of 256 men with mCRPC and an independent validation cohort of 92 men with mCRPC. In both cohorts, men receiving proton pump inhibitors and those with non-castrate levels of testosterone (>50 ng/dl) were excluded. Serum CGA was measured in a homogeneous automated immunofluorescent assay using time-resolved amplified cryptate emission. In the validation cohort, CTC enumeration was also performed using the FDA cleared CELLSEARCH®CTC test. Cox proportional hazard regression models were used for prognostic association of serum CGA and CTC counts with overall survival. RESULTS: In the screening cohort 200 men were eligible for analysis. The median serum CGA was 100.3 ng/mL (interquartile range 67–161.3) and 34/200 were above the reference range. In the subset of men with Gleason scores ≥ 8, elevated CGA was associated with shorter overall survival [hazard ratio (HR) 2.19, p = 0.017]. In the validation cohort for 71 men eligible for analysis the median serum CGA was 90 ng/mL (interquartile range 55–156) and 31/71 patients had an elevated CGA. 51% of patients had a Gleason score ≥8 and 66/71 patients had CTCs enumerated with 26/66 with a CTC count ≥ 5 per 7.5ml blood sample (unfavorable). Both elevated serum CGA (HR 1.91, p = 0.043) and unfavorable CTC counts (HR 2.97, p = 0.0012) were adversely associated with overall survival and patients with ≥ 5 CTCs and elevated serum CGA had the shortest overall survival (HR 3.76, p = 0.008). CONCLUSION: Elevated serum CGA was negatively associated with OS in men with mCRPC. Serum CGA represents a prognostic biomarker that may complement CTC enumeration.