Minimal residual marrow disease: Detection and significance of isolated tumour cells in bone marrow

Background: Detection of malignant cells in bone marrow and peripheral blood of patients with solid tumours at the time of surgery is increasingly emerging as a prognostic factor for disease progression and a way of monitoring adjuvant therapies. Furthermore, isolation and characterization of these cells provide insight into the early metastatic process, with potential therapeutic implications. This article reviews the current knowledge about the clinical significance of minimal residual marrow disease (MRMD) and its methods of detection, outlining some of their specific technical problems. Methods: A comprehensive review of articles cited in the largest medical databases was conducted. Results: The sensitivity of the methods of detecting MRMD has improved substantially in the past decade, resulting in higher detection rates. In many solid tumours MRMD has been found to correlate with disease-free and overall survival; however, the importance of this as an independent prognostic variable remains contentious. Conclusions: There is a need for a standardized approach to the detection of these cells before they become integrated into the current staging systems. The challenge remains to establish which of these tumour cells have the capacity to progress and develop metastatic disease, what are the early genetic and molecular mechanisms underlying this process and to apply novel, better targeted therapies against them.