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

2 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
Externally publishedYes

Bibliographical note

Funding Information:
Epic Sciences provided facilities, materials and services to perform isolation and sequencing of circulating tumour cells. Work at Memorial Sloan Kettering Cancer Center (MSK) was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, and funded in part by the NIH/NCI Cancer Center Support Grant to MSK ( P30 CA008748 ), the NIH/NCI SPORE in Prostate Cancer grant to MSK ( P50 CA092629 ), the Prostate Cancer Foundation and the Prostate Cancer Clinical Trials Consortium. J.L. Zhao is supported by an NIH/NCI NRSA training award to MSK ( T32 CA009207 ), an ASCO Conquer Cancer Young Investigator Award, and a K12 Paul Calabresi Career Development Award for Clinical Oncology. Dr. Armstrong was supported by a Prostate Cancer Foundation grant and 1R01CA233585-01 , and the DCI P30 CA014236 as well as Duke Cancer Institute shared resources for biostatistics. This work was partially funded by Department of Defense grant W81XWH-14-2-0179 and NIH/NCI grant 1R01CA256157-01 .

Publisher Copyright:
© 2021

Keywords

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

PubMed: MeSH publication types

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

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