Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer.
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.
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.
David
D
Lorente
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.
David
D
Olmos
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Joaquin
J
Mateo
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Diletta
D
Bianchini
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
George
G
Seed
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Martin
M
Fleisher
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Daniel C
DC
Danila
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Penny
P
Flohr
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Mateus
M
Crespo
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Ines
I
Figueiredo
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.
Susana
S
Miranda
Medical Affairs, Janssen Diagnostics, Beerse, Belgium.
Kurt
K
Baeten
Janssen Research & Development, Menlo Park, CA, USA.
Arturo
A
Molina
Janssen Research & Development, La Jolla, CA, USA.
Thian
T
Kheoh
Janssen Research & Development, Menlo Park, CA, USA.
Robert
R
McCormack
MIRA Research Institute for Biomedical Technology and Technical Medicine, University of Twente, Twente, The Netherlands.
Leon W M M
LW
Terstappen
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Howard I
HI
Scher
Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK. Electronic address: johann.de-Bono@icr.ac.uk.
Johann S
JS
de Bono
D000736:Androstenes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002452:Cell Count; D002986:Clinical Trials as Topic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology
D000736:Androstenes; C089740:abiraterone; D011241:Prednisone
Abiraterone; Castration-resistant prostate cancer; Chemotherapy; Circulating tumor cells; Response; Treatment outcome