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

Prostate Cancer and Prostatic Diseases volume 21, pages 431–437 (2018)Cite this article

Subjects

Abstract

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 7.5 ml 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.

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Acknowledgements

This study is supported in part by R01 CA21209 to MK; Joseph and Gail Gassner support to MK; and for the prospective clinical trial that performed the CTC collections by the Mayo Clinic Center for Individualized Medicine with support for MK, DH, RC.

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Authors and Affiliations

  1. Department of Oncology, Mayo Clinic, Rochester, MN, USA

    Karthik V. Giridhar, Cristobal Sanhueza, Hassan Alkhateeb, Brian A. Costello, Fernando Quevedo, Lance Pagliaro & Manish Kohli

  2. Department of Oncology, Clínica Santa María, Santiago, Chile

    Cristobal Sanhueza

  3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    David W Hillman & Rachel Carlson

  4. Department of Medicine, Mayo Clinic, Jacksonville, FL, USA

    Winston Tan

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  1. Karthik V. Giridhar
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Correspondence to Manish Kohli.

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Giridhar, K.V., Sanhueza, C., Hillman, D.W. et al. Serum chromogranin-A-based prognosis in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 21, 431–437 (2018). https://doi.org/10.1038/s41391-018-0046-9

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