Adequately assessing patient response to treatment is a significant challenge in the management of patients with castration-resistant prostate cancer (CRPC). Changes in circulating tumor cells (CTCs) can identify patients with CRPC who are not benefiting from therapy as early as 4 weeks posttreatment, according to the results of a post-hoc analysis conducted by David Lorente, MD, Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research, Sutton, United Kingdom, and colleagues (Lorente D, et al. Eur Urol. 2016 Jun 8. Epub ahead of print). Citing recent data, the investigators’ documentation of CTC counts has emerged as a powerful biomarker for assessing prognosis and treatment response in patients with CRPC. “It is envisaged that validation of these results in further prospective clinical trials could contribute to testing trial-level surrogacy so that CTC counts could become a clinical trial endpoint to accelerate drug approval for advanced CRPC,” they said. Using data from the COU-AA-301 and IMMC-38 clinical trials, Dr Lorente and colleagues conducted a post-hoc analysis of information for patients with CRPC and baseline CTCs of ≥5 cells/7.5 mL, and assessed the value of a 30% CTC decline at weeks 4, 8, and 12 as a treatment response biomarker. In the phase 3 clinical trial OU-AA-301, patients with CRPC received abiraterone plus prednisone or placebo plus prednisone postchemotherapy; IMMC-38 was a prospective, open-label trial of patients with CRPC who received chemotherapy. A total of 486 patients from the IMMC-38 and COU-AA-301 trials were included in the analysis. The median follow-up time for both trials was 11.2 months, and the median overall survival (OS) was comparable groups. A 30% decline in CTC count was seen at weeks 4, 8, and 12 in 283 (64.3%) patients, 248 (65.3%) patients, and 226 (64.4%) patients, respectively. This decline was associated with better survival, and was consistent between data sets from both clinical trials. Compared with a progressive, increased CTC count, a stable CTC count (ie, <30% fall or <30% increase) was not associated with a significant OS benefit. A total of 113 (23.1%) patients achieved a 50% prostate-specific antigen (PSA) response. In both trials, PSA response was significantly associated with a 30% CTC decline at weeks 4, 8, and 12. “This pooled post hoc analysis for 2 prospective clinical trials shows that a 30% CTC decline as early as 4 wk [weeks] after treatment initiation can effectively distinguish between patients benefiting from improved OS and patients not benefiting from treatment who may require a switch to an alternative therapeutic regimen,” said Dr Lorente and colleagues. “We previously reported separate data showing that a 30% CTC decline was associated with improved OS in a smaller cohort. Using larger prospective series, we now report that a posttreatment 30% CTC decline is associated with longer OS in patients treated with abiraterone plus prednisone, corticosteroids alone, and chemotherapy,” the investigators concluded.