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

Eur J Cancer. 2021 Jun:150:83-94. doi: 10.1016/j.ejca.2021.02.042. Epub 2021 Apr 21.

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.

Keywords: Biomarker; CTC; Prognosis; Prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Androstenes / therapeutic use
  • Benzamides / therapeutic use
  • Biomarkers, Tumor / blood
  • Cell Count
  • Clinical Decision-Making
  • Humans
  • Keratins / blood
  • Leukocyte Common Antigens / blood
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / chemistry
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology*
  • Nitriles / therapeutic use
  • Phenylthiohydantoin / therapeutic use
  • Predictive Value of Tests
  • Progression-Free Survival
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Reproducibility of Results

Substances

  • Androgen Antagonists
  • Androstenes
  • Benzamides
  • Biomarkers, Tumor
  • Nitriles
  • Phenylthiohydantoin
  • Keratins
  • enzalutamide
  • Leukocyte Common Antigens
  • PTPRC protein, human
  • abiraterone

Associated data

  • ClinicalTrials.gov/NCT02269982