Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer

H. I. Scher, A. J. Armstrong, J. D. Schonhoft, A. Gill, J. L. Zhao, E. Barnett, E. Carbone, J. Lu, E. S. Antonarakis, J. Luo, S. Tagawa, C. H. dos Anjos, Q. Yang, D. George, R. Szmulewitz, D. C. Danila, R. Wenstrup, M. Gonen, S. Halabi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). Patients and methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3–3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1–3.0] for OS and 1.7 [1.1–2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). Conclusion: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalEuropean Journal of Cancer
Volume150
DOIs
StatePublished - Jun 2021

Keywords

  • Biomarker
  • CTC
  • Prognosis
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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