Methods for isolation, detection and characterization of circulating tumor cells in epithelial ovarian carcinoma and summarized evidence of their association with survival outcome: a scoping review.

Increasing evidence suggests that circulating tumor cells (CTCs) are associated with poorer survival in epithelial ovarian carcinoma (EOC). In this scoping review, we systematically reviewed and mapped available evidence on CTC sampling, isolation, detection, and characterization methods in EOC that may introduce bias when analyzing CTC association with survival. PubMed, Scopus, and Web of Science were searched for eligible studies. Of 977 records identified, 71 studies met the inclusion criteria. Serous EOC was the most commonly studied histotype, although cohorts also included other EOC histotypes and/or unspecified ovarian cancer subtypes, as well as all disease stages (I-IV). A substantial variety of isolation methods were identified across included studies; out of 22 distinct CTC isolation methods, 38/71 were based on biological properties: mainly morphological, immunophenotypic and molecular-based methods (38/71), followed by 25/71 physical and 8/71 hybrid approaches. Immunofluorescence-based detection was used in 66/71 studies, through imaging-based, flow-cytometric, and fluorescent in-situ hybridization methods. Reported cutoff values for defining CTC-positive patients varied from 1-8 CTCs/mL or CTC/sample, while CTC median positivity rate in EOC was 66.7% (range 12-100%), although some studies did not report such details. Associations of CTCs with survival outcomes in EOC were reported in 26/71 studies, with 14 demonstrating significantly shorter progression-free and/or overall survival in CTC-positive patients. To further investigate and understand the prognostic significance of CTCs in EOC, future studies should focus on improving standardization of methods used and transparency in reporting data, while harmonizing CTC cutoffs and study design to improve comparability among them.