Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study

Abstract

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® 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 D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® 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% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 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® system) were confirmed. Conclusion: CTC detection at D28 and the D0–D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.

Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

“…In addition to being able to predict patient prognosis, several clinical trials have demonstrated the usefulness of CTCs in monitoring or guiding clinical therapy [ 46 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ] ( Table 2 ). For example, longitudinal studies evaluating CTC status of patients following ALK inhibitor treatment revealed elimination of CTCs after treatment could predict disease remission [ 85 ].…”

Liquid Biopsy and Primary Brain Tumors

“…The collection of a sufficient amount of CSF may appear to be an additional challenge for children with brain tumors, such as medulloblastomas, but usually not for adults; it is also possible to use a previously implanted shunt from the ventricle to collect CSF. In carcinomas, the number of CTCs was correlated with time of survival, i.e., patients with more than a certain number died early, while others survived up to 10 times longer [ 35 ].…”

Assessment of a Size-Based Method for Enriching Circulating Tumour Cells in Colorectal Cancer

“…Previous work with CellSearch has demonstrated that it can routinely enrich CTCs and offer prognostication in many solid cancers, such as breast, colon, and prostate cancers. For example, a study in colorectal cancer patients demonstrated that patients who yielded at least two CTCs had a shorter overall survival (OS) and progression-free survival (PFS) of 10.28 and 5.28 months respectively, compared with those of patients who had ≤1 CTC (OS = 24.84 months; PFS = 8.28 months) [ 16 ], highlighting the impact of greater CTC burden, especially after treatment, on the OS and PFS in patients [ 8 , 16 ].…”