Serum chromogranin-A-based prognosis in metastatic castration-resistant prostate cancer.

Karthik V Giridhar,Winston Tan,David W Hillman,Manish Kohli,Hassan Alkhateeb,Rachel Carlson,Brian A Costello,Cristobal Sanhueza,Lance Pagliaro,Fernando Quevedo

doi:10.1038/s41391-018-0046-9

Karthik V Giridhar, Winston Tan + Show 8 more

Open Access

https://doi.org/10.1038/s41391-018-0046-9

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Abstract

ObjectiveTo 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 methodsA 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.ResultsIn 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).ConclusionElevated serum CGA was negatively associated with OS in men with mCRPC. Serum CGA represents a prognostic biomarker that may complement CTC enumeration.

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