Approximately 15% of men with newly diagnosed prostate cancer have high-risk features that increase the risk of recurrence and metastasis. Better predictive biomarkers could allow for earlier detection of biochemical recurrence (BCR) and change surveillance and adjuvant treatment paradigms. Circulating tumor cells (CTCs) are thought to represent the earliest form of metastases, however their role as biomarkers in men with high-risk localized prostate cancer (HRLPCa) is not well defined.

Blood samples from 37 patients with HRLPCa (Stage T3a or higher, Gleason score ≥8, or PSA ≥20 ng/ml), were obtained 2-5 months post prostatectomy. CTCs were enumerated using the Epic Sciences platform. Matched tumor and single CTC sequencing was performed.

CTCs were detected in 81.1% (30/37) of samples with a median of 2.4 CTCs/ml (range: 0-22.9). Patients with detectable CTCs exhibited a trend towards shorter recurrence times (p=0.12) and all patients with BCR had detectable CTCs. AR over-expression was detected in 18.9% (7/37) of patients. Patients with BCR had more CTC copy number aberrations (CNAs, p=0.027). Matched tumor tissue and single CTC sequencing reveals heterogeneity.

There was a high incidence of CTC detection after RP and shorter time to BCR in those with higher CTC burden and more CTC CNAs. Genomic alterations consistent with established CNAs in prostate cancer were detectable in CTCs, but often discordant with cells analyzed in bulk from primary lesions. With further testing in appropriately powered cohorts, early CTC detection could be an informative biomarker to assist with adjuvant treatment decisions.

The Journal of urology. 2019 Jun 19 [Epub ahead of print]

Terence W Friedlander, Christopher Welty, Archana Anantharaman, Joseph D Schonhoft, Adam Jendrisak, Jerry Lee, Patricia Li, Jeffrey Hough, Alise Stromlund, Yasuko Kobayashi, Jeffry Simko, Nathan Farrokhian, Karla Lindquist, Stephanie Greene, Priscilla Ontiveros, Ryon Graf, Angel Rodriquez, Mahipal Suraneni, Yipeng Wang, Mark Landers, Peter Carroll, Matthew R Cooperberg, Ryan Dittamore, Pamela L Paris

Division of Hematology-Oncology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco , San Francisco , CA ., Epic Sciences . San Diego , CA., Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco , San Francisco , CA., Department of Pathology, University of California at San Francisco , San Francisco , CA.