Journal
CANCER DISCOVERY
Volume 8, Issue 3, Pages 288-303Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-16-1406
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Funding
- Prostate Cancer Foundation
- Charles Evans Foundation
- Department of Defense [W81XWH-12-1-0153]
- Howard Hughes Medical Institute
- National Institute of Biomedical Imaging and Bioengineering [2U01EB012493]
- National Institute of General Medical Sciences [T32GM007753]
- NIH, National Cancer Institute [2R01CA129933]
- Burroughs Wellcome Fund
- MGH-Johnson & Johnson Center for Excellence in CTC Technologies
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Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTCM score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with <= 12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTCL score predicts microscopic dissemination to seminal vesicles and/or lymph nodes (P < 0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer. SIGNIFICANCE: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. (c) 2018 AACR.
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