Detection and clinical importance of micrometastatic disease

Metastatic relapse in patients with solid tumors is caused by systemic preo perative or perioperative dissemination of tumor cells. The presence of ind ividual tumor cells in bone marrow and in peripheral blood can be detected by immunologic or molecular methods and is being regarded increasingly as a clinically relevant prognostic factor. Because the goal of adjuvant therap y is the eradication of occult micrometastatic tumor cells before metastati c disease becomes clinically evident, the early detection of micrometastase s could identify the patients who are most land least) likely to benefit fr om adjuvant therapy, In addition, more sensitive methods for detecting such cells should increase knowledge about the biologic mechanisms of metastasi s and improve the diagnosis and treatment of micrometastatic disease. In co ntrast to solid metastatic tumors, micrometastatic tumor cells are appropri ate targets for intravenously applied agents because macromolecules and imm unocompetent effector cells should have access to the tumor cells. Because the majority of micrometastatic tumor cells may be nonproliferative (G(0) p hase), standard cytotoxic chemotherapies aimed at proliferating cells may b e less effective, which might explain, in part, the failure of chemotherapy , Thus, adjuvant therapies that are aimed at dividing and quiescent cells, such as antibody-based therapies, are of considerable interest, From a lite rature search that used the databases MEDLINE(R), CANCERLIT(R), Biosis(R), Embase(R), and SciSearch(R), we discuss the current state of research on mi nimal residual cancer in patients with epithelial tumors and the diagnostic and clinical implications of these findings.