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

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

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Atrasentan
  • Biomarkers, Tumor / blood
  • Castration
  • Cell Count
  • Disease Progression
  • Docetaxel
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplastic Cells, Circulating*
  • Prognosis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology*
  • Pyrrolidines / therapeutic use*
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Pyrrolidines
  • Taxoids
  • Docetaxel
  • Atrasentan

Associated data

  • ClinicalTrials.gov/NCT00134056

Grant support