Treatment response biomarkers are urgently needed for castration-resistant prostate cancer (CRPC). Baseline and post-treatment circulating tumor cell (CTC) counts of ≥5 cells/7.5ml are associated with poor CRPC outcome.
To determine the value of a ≥30% CTC decline as a treatment response indicator.
We identified patients with a baseline CTC count ≥5 cells/7.5ml and evaluable post-treatment CTC counts in two prospective trials.
Patients were treated in the COU-AA-301 (abiraterone after chemotherapy) and IMMC-38 (chemotherapy) trials.
The association between a ≥30% CTC decline after treatment and survival was evaluated using univariable and multivariable Cox regression models at three landmark time points (4, 8, and 12 wk). Model performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and c-indices.
Overall 486 patients (122 in IMMC-38 and 364 in COU-AA-301) had a CTC count ≥5 cells/7.5ml at baseline, with 440, 380, and 351 patients evaluable at 4, 8, and 12 wk, respectively. A 30% CTC decline was associated with increased survival at 4 wk (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.36-0.56; p<0.001), 8 wk (HR 0.41, 95% CI 0.33-0.53; p<0.001), and 12 wk (HR 0.39, 95% CI 0.3-0.5; p<0.001) in univariable and multivariable analyses. Stable CTC count (<30% fall or <30% increase) was not associated with a survival benefit when compared with increased CTC count. The association between a 30% CTC decline after treatment and survival was independent of baseline CTC count. CTC declines significantly improved the AUC at all time-points. Finally, in the COU-AA-301 trial, patients with CTC ≥5 cells/7.5ml and a 30% CTC decline had similar overall survival in both arms.
A 30% CTC decline after treatment from an initial count ≥5 cells/7.5ml is independently associated with CRPC overall survival following abiraterone and chemotherapy, improving the performance of a multivariable model as early as 4 wk after treatment. This potential surrogate must now be prospectively evaluated.
Circulating tumor cells (CTCs) are cancer cells that can be detected in the blood of prostate cancer patients. We analyzed changes in CTCs after treatment with abiraterone and chemotherapy in two large clinical trials, and found that patients who have a decline in CTC count have a better survival outcome.
European urology. 2016 Jun 08 [Epub ahead of print]
David Lorente, David Olmos, Joaquin Mateo, Diletta Bianchini, George Seed, Martin Fleisher, Daniel C Danila, Penny Flohr, Mateus Crespo, Ines Figueiredo, Susana Miranda, Kurt Baeten, Arturo Molina, Thian Kheoh, Robert McCormack, Leon W M M Terstappen, Howard I Scher, Johann S de Bono
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK; Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain., Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; CNIO-IBIMA Genitourinary Cancer Unit, Department of Medical Oncology, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga, Spain., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK., Medical Affairs, Janssen Diagnostics, Beerse, Belgium., Janssen Research & Development, Menlo Park, CA, USA., Janssen Research & Development, La Jolla, CA, USA., Janssen Research & Development, Menlo Park, CA, USA., MIRA Research Institute for Biomedical Technology and Technical Medicine, University of Twente, Twente, The Netherlands., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK. Electronic address: .