Clinical Relevance Of Viable Circulating Tumor Cells In Patients With Metastatic Colorectal Cancer: The Colospot Prospective Study

Simple Summary The analysis of circulating tumor cells (CTCs) as a "real-time liquid biopsy" in epithelial tumors for personalized medicine has received tremendous attention over the past years, with important clinical implications. In metastatic colorectal cancer (mCRC), the CellSearch(R) system has already demonstrated its prognostic value and interest in monitoring treatment response, but the number of recovered CTCs remains low. In this article, we evaluate the early prognostic and predictive value of viable CTCs in patients with mCRC treated with FOLFIRI-bevacizumab with an alternative approach, the functional EPISPOT assay. This study shows that viable CTCs can be detected in patients with mCRC before and during FOLFIRI-bevacizumab treatment and that CTC detection at D-28 and the D-0-D-28 CTC kinetics evaluated with the EPISPOT assay are associated with response to treatment.Background: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch(R) system in patients with metastatic colorectal cancer (mCRC). Methods: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D-0, D-14, D-28, D-42, and D-56 (EPISPOT assay) and at D-0 and D-28 (CellSearch(R) system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan-Meier method and log-rank test. Results: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D-0), 15% (D-14), 12% (D-28), 10% (D-42), and 12% (D-56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D-0 and D-28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of >= 3 CTCs (CellSearch(R) system) were confirmed. Conclusions: CTC detection at D-28 and the D-0-D-28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.