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Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide.

Publication ,  Journal Article
Brown, LC; Halabi, S; Schonhoft, JD; Yang, Q; Luo, J; Nanus, DM; Giannakakou, P; Szmulewitz, RZ; Danila, DC; Barnett, ES; Carbone, EA; Gill, A ...
Published in: Clin Cancer Res
July 15, 2021

PURPOSE: While the detection of AR-V7 in circulating tumor cells (CTC) is associated with resistance to abiraterone or enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), it only accounts for a minority of this resistance. Neuroendocrine (NE) differentiation or chromosomal instability (CIN) may be additional mechanisms that mediate resistance. EXPERIMENTAL DESIGN: PROPHECY was a multicenter prospective study of men with high-risk mCRPC starting abiraterone or enzalutamide. A secondary objective was to assess Epic CTC CIN and NE phenotypes before abiraterone or enzalutamide and at progression. The proportional hazards (PH) model was used to investigate the prognostic importance of CIN and NE in predicting progression-free survival and overall survival (OS) adjusting for CTC number (CellSearch), AR-V7, prior therapy, and clinical risk score. The PH model was utilized to validate this association of NE with OS in an external dataset of patients treated similarly at Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY). RESULTS: We enrolled 118 men with mCRPC starting on abiraterone or enzalutamide; 107 were evaluable on the Epic platform. Of these, 36.4% and 8.4% were CIN positive and NE positive, respectively. CIN and NE were independently associated with worse OS [HR, 2.2; 95% confidence interval (CI), 1.2-4.0 and HR 3.8; 95% CI, 1.2-12.3, respectively] when treated with abiraterone/enzalutamide. The prognostic significance of NE positivity for worse OS was confirmed in the MSKCC dataset (n = 173; HR, 5.7; 95% CI, 2.6-12.7). CONCLUSIONS: A high CIN and NE CTC phenotype is independently associated with worse survival in men with mCRPC treated with abiraterone/enzalutamide, warranting further prospective controlled predictive studies to inform treatment decisions.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 15, 2021

Volume

27

Issue

14

Start / End Page

4077 / 4088

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prostatic Neoplasms, Castration-Resistant
  • Prospective Studies
  • Phenylthiohydantoin
  • Phenotype
  • Oncology & Carcinogenesis
  • Nitriles
  • Neurosecretory Systems
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brown, L. C., Halabi, S., Schonhoft, J. D., Yang, Q., Luo, J., Nanus, D. M., … Armstrong, A. J. (2021). Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide. Clin Cancer Res, 27(14), 4077–4088. https://doi.org/10.1158/1078-0432.CCR-20-3471
Brown, Landon C., Susan Halabi, Joseph D. Schonhoft, Qian Yang, Jun Luo, David M. Nanus, Paraskevi Giannakakou, et al. “Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide.Clin Cancer Res 27, no. 14 (July 15, 2021): 4077–88. https://doi.org/10.1158/1078-0432.CCR-20-3471.
Brown, Landon C., et al. “Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide.Clin Cancer Res, vol. 27, no. 14, July 2021, pp. 4077–88. Pubmed, doi:10.1158/1078-0432.CCR-20-3471.
Brown LC, Halabi S, Schonhoft JD, Yang Q, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ, Danila DC, Barnett ES, Carbone EA, Zhao JL, Healy P, Anand M, Gill A, Jendrisak A, Berry WR, Gupta S, Gregory SG, Wenstrup R, Antonarakis ES, George DJ, Scher HI, Armstrong AJ. Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide. Clin Cancer Res. 2021 Jul 15;27(14):4077–4088.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 15, 2021

Volume

27

Issue

14

Start / End Page

4077 / 4088

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Prostatic Neoplasms, Castration-Resistant
  • Prospective Studies
  • Phenylthiohydantoin
  • Phenotype
  • Oncology & Carcinogenesis
  • Nitriles
  • Neurosecretory Systems
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis