JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

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

Amir Goldkorn, Benjamin Ely, David I Quinn, Catherine M Tangen, Louis M Fink, Tong Xu, Przemyslaw Twardowski, Peter J Van Veldhuizen, Neeraj Agarwal, Michael A Carducci, J Paul Monk, Ram H Datar, Mark Garzotto, Philip C Mack, Primo Lara, Celestia S Higano, Maha Hussain, Ian Murchie Thompson, Richard J Cote, Nicholas J Vogelzang
Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 2014 April 10, 32 (11): 1136-42
24616308

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.

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