Abstract 1136: Detection and characterization of circulating tumor cells in localized and metastatic prostate cancer patients using CTC-Chip microfluidic technology

Despite recent molecular advances, the treatment of localized and metastatic prostate cancer has changed little in recent decades and it remains a major cause of cancer deaths in men. Localized prostate cancer may be either indolent or invasive, without reliable distinguishing markers, and the absence of tumor tissue from patients with metastatic bone disease has hampered understanding of acquired resistance to primary hormonal therapy. Given the predominant hematogenous spread of prostate cancer, circulating tumor cells (CTCs) may provide an indicator of vascular invasiveness, as well as a source of tumor specimens for molecular analysis, but available technologies have been limited by relatively low sensitivity. Huge strides in engineering at smaller scales have lead to the tremendous progress in microfabricated devices to facilitate both applied and basic research. Applying a multi-disciplinary approach, we have developed a microfluidic technology “CTC-Chip” for diagnosis and monitoring of non-hematological cancers. Using the CTC-Chip, we were able to isolate CTCs in patients with both localized and metastatic prostate cancer. In patients with advanced cancer, CTCs were present at a frequency of 34 CTCs/mL (range 14-653), with a profound decline in numbers during response to hormone withdrawal therapy. Molecular markers, including the characteristic TMPRSS2-ERG translocation, are readily identified in CTCs. In patients with early stage, resectable prostate cancer, we have monitored CTC load in circulation following surgical resection of the primary tumor. CTCs were examined the day following surgical resection, at postoperative day 9, and at greater than 3 months, coincident with scheduled postoperative clinical visits. Longitudinal monitoring of CTCs revealed all CTC-positive cases showed disappearance of CTCs following prostate resection, with some having an immediate decline and others having a delayed (>24 hours) response. No evident differences in tumor pathology or operative procedure distinguished patients with a rapid versus delayed postoperative CTC decline. Dual staining of captured CTCs for PSA and Ki67 indicated a broad range in proliferative index of CTCs among patients with different clinical courses. Thus, the quantitative isolation and analysis of CTCs in both localized and metastatic prostate cancer provides novel insights into early hematogenous dissemination and enables molecular analyses of treatment-responsive and -resistant disease