Clinical significance of CTC enumeration on the Epic Sciences platform in metastatic castration-resistant prostate cancer (mCRPC) patients treated with AR signaling inhibitors (ARSi).

Abstract

5571 Background: Circulating Tumor Cell (CTC) number, enumerated using the analytically valid FDA cleared Cell Search (Menarini Silicon Biosystems) platform has been shown to be prognostic for survival pre- and post-therapy, and used as an aid to monitoring breast, colorectal and prostate cancers. The assay uses antibody-based capture and defines a CTC as an EpCAM+ and CD45- intact cell. In contrast, with the Epic sciences CTC detection platform red blood cells are first lysed and all nucleated cells deposited on pathology slides, fixed, and imaged. There is no affinity selection and CTCs for this analysis were defined in silico as any cytokeratin (CK)+, CD45- cell with an intact DAPI+ nucleus. Here we report the prognostic significance of the CK+ CTCs detected on the EPIC Sciences platform in mCRPC patients prior to treatment with an AR signaling inhibitor. Methods: A pre-treatment blood sample was collected from 181 unique patients with progressing mCRPC about to start an ARSI as 1st, 2nd or 3rd line therapy at MSKCC. CTCs were enumerated on the Epic Sciences platform and verified by a trained human technician. Results: At least 1 CTC was detected (median = 1, 0-711 CTCs/ml) in 134 (74%) of cases, with higher counts observed in patients with visceral or multiple osseous sites relative to those with lymph node only disease. Counts increased by line of therapy. The table shows the associated risk of death for CTCs modeled as a continuous variable. Conclusions: The results support the clinical validity of CTC number determined on the Epic Sciences platform as a significant baseline prognostic factor. In multivariate modeling CTC number was found to be the most significant blood-based predictor of poor OS with each doubling representing a 20% greater risk of death observed with adjustment for therapy line, LDH, PSA, and ALK. [Table: see text]