H I Scher1, A J Armstrong2, J D Schonhoft3, A Gill3, J L Zhao4, E Barnett4, E Carbone4, J Lu3, E S Antonarakis5, J Luo5, S Tagawa6, C H Dos Anjos4, Q Yang7, D George8, R Szmulewitz9, D C Danila10, R Wenstrup3, M Gonen4, S Halabi11. 1. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: Scherh@mskcc.org. 2. Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. Electronic address: andrew.armstrong@duke.edu. 3. Epic Sciences, San Diego, CA, USA. 4. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Johns Hopkins University, Baltimore, MD, USA. 6. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 7. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA. 8. Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. 9. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA; University of Chicago, Chicago, IL, USA. 10. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 11. Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Abstract
PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
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