Approximately 20% men with metastatic castration-sensitive prostate cancer (mCSPC) progress within one-year of treatment, and biomarkers to identify them upfront are lacking. In a randomized phase III trial in mCSPC men (SWOG S1216); higher baseline circulating tumor cells (CTCs) were prognostic of inferior outcomes. We aimed to validate these findings and interrogate corresponding tumor genomic profiles. Consecutively seen men with newly diagnosed mCSPC undergoing systemic therapy and baseline CTCs enumeration by CellSearch assay were included. Gene alterations were determined by comprehensive genomic profiling of tumor tissue by CLIA-certified lab. The relationship between categorized CTC counts and both progression-free survival (PFS) and overall survival (OS) was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason score, PSA at ADT initiation, disease volume, de novo status, treatment intensification and number of altered genes. Overall, 103 patients were included in the analysis. On multivariate analysis high CTCs (≥5 vs. 0) were associated with poorer PFS (hazard ratio (HR) 4.52; 95% CI 1.84-11.11, p=0.001) and OS (HR 3.59; 95% CI 0.95-13.57, p=0.060). Patients with higher CTC counts had a greater number of altered genes and total number of alterations (all p<0.02). Herein, we, for the first time, externally validate the association of higher CTC counts with inferior survival outcomes in men with mCSPC and show a distinct associated tumor genomic landscape. These findings may improve prognostication, counseling of patients, and treatment selection in men with mCSPC.
Molecular cancer therapeutics. 2022 Oct 05 [Epub ahead of print]
Umang Swami, Nicolas Sayegh, Yeonjung Jo, Benjamin Haaland, Taylor R McFarland, Roberto H Nussenzveig, Divyam Goel, Deepika Sirohi, Andrew W Hahn, Benjamin L Maughan, Amir Goldkorn, Neeraj Agarwal
University of Utah/Huntsman Cancer Institute, Salt lake City, UT, United States., Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City, Utah, United States., Huntsman Cancer Institute; University of Utah, Salt Lake City, UT, United States., University of Utah/Huntsman Cancer Institute, Salt Lake City, UT, United States., University of Utah, Salt Lake City, Utah, United States., The University of Texas MD Anderson Cancer Center, Houston, TX, United States., University of Utah/Huntsman Cancer Institute, Salt Lake City, Utah, United States., Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, Los Angeles, United States.