Disseminated tumor cells: diagnosis, prognostic value, phenotyping and therapeutic strategy

The incidence of local relapse after complete (RO) resection of solid tumors is largely determined by the skill of the surgeon, whereas metastatic relapse in distant organs is caused by pre-or perioperative systemic dissemination of tumor cells. The presence of individual disseminated tumor cells - e.g., in bone marrow as indicator organ - can be detected by sensitive immunocytochemical and molecular methods and is increasingly considered as a clinically relevant prognostic indicator. In contrast to solid metastases, isolated micrometastatic tumor cells are appropriate targets for intravenously applied anti-cancer therapeutics because they are easily accessible to macromolecules and immunologic effector cells. The majority of these tumor cells appear to be nonproliferating (i. e., in the GO phase of the cell cycle), which may explain the failure of adjuvant chemotherapy. Adjuvant therapeutic strategies aimed at quiescent tumor cells are therefore of increasing interest. This therapeutic rationale has been tested and confirmed in a randomized clinical trial using antibody 17-1A in patients with non-metastatic colorectal carcinoma (UICC stage III). The antibody therapy kills also quiescent tumor cells ("dormant cells") and is independent from a potential chemotherapy resistance of the tumor cells. As treatment for minimal residual cancer, the clinical use of antibody therapy could be envisaged in conjunction with chemotherapy, applied either in parallel or sequentially. The aim of this review is to present and discuss the current state of research in the field of diagnosis and therapy of minimal residual cancer.