[Disseminated and circulating tumor cells in gastrointestinal oncology]

Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.