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J Clin Oncol. 2014 Apr 10;32(11):1136-42. doi: 10.1200/JCO.2013.51.7417. Epub 2014 Mar 10.

Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.

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1
Amir Goldkorn, David I. Quinn, and Tong Xu, University of Southern California Keck School of Medicine and Norris Comprehensive Cancer Center, Los Angeles; Przemyslaw Twardowski, City of Hope, Duarte; Philip C. Mack and Primo Lara Jr, University of California, Davis, Sacramento, CA; Benjamin Ely and Catherine M. Tangen, Southwest Oncology Group Statistical Center; Celestia S. Higano, Puget Sound Oncology Consortium, Seattle Cancer Care Alliance, and University of Washington, Seattle, WA; Louis M. Fink, Nevada Cancer Institute; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada and US Oncology Research, Las Vegas, NV; Peter J. Van Veldhuizen, University of Kansas Cancer Center, Westwood, KS; Neeraj Agarwal, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Michael A. Carducci, Johns Hopkins Kimmel Cancer Center and Eastern Cooperative Oncology Group, Baltimore, MD; J. Paul Monk III, Ohio State University and Cancer and Leukemia Group B, Columbus, OH; Ram H. Datar and Richard J. Cote, University of Miami Miller School of Medicine, Miami, FL; Mark Garzotto, Portland Veterans Affairs Medical Center, Portland, OR; Maha Hussain, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; and Ian Murchie Thompson Jr, University of Texas Health Science Center at San Antonio, San Antonio, TX.

Abstract

PURPOSE:

Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan.

PATIENTS AND METHODS:

CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees.

RESULTS:

Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55).

CONCLUSION:

These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00134056.

PMID:
24616308
PMCID:
PMC3970171
DOI:
10.1200/JCO.2013.51.7417
[Indexed for MEDLINE]
Free PMC Article

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