Published in Cancer Detection and Prevention 2000; 24(4):376-403.

Detection of Minimal Residual Disease in Patients with Cancer: A Review of Techniques, Clinical Implications, and Emerging Therapeutic Consequences

Wolfgang J. Köstler,a Thomas Brodowicz,a Michael Hejna,a Christoph Wiltschke. MD,a and Christoph C. Zielinski, MDa,b

aClinical Division of Oncology, Department of Medicine I, University Hospital, and bLudwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria

Address all correspondence and reprint requests to: Prof. Dr. Christoph C. Zielinski, Department of Medicine I, 18-20 Wahringer Gürtel, A-1090 Vienna, Austria.

ABSTRACT: The issue of minimal residual disease (MRD) manifesting itself by the presence of undetected disseminated isolated tumor cells in both tissues and hematopoietic autografts from patients with early-stage malignancies or from patients in clinical complete remission has been discussed widely during the last decade. Based on the current understanding of the pathogenesis of malignancy, disseminated tumor cells persisting after conventional oncologic treatment modalities or after reinfusion of contaminated autologous hematopoietic cells constitute the source of subsequent recurrence of disease. Accordingly, much emphasis is placed on the detection and characterization of disseminated isolated tumor cells in both basic and clinical research. This effort is aimed at a better understanding of the processes of metastasis and tumor dormancy and, ultimately, the estimation of prognosis, molecular monitoring, and the design of new therapeutic agents in oncology. In our review, we used computerized (MEDLINE, Embase) and manual searches to summarize laboratory and clinical data concerning MRD focusing on the issue of MRD in solid malignancies. We give a detailed overview of the methods used for the detection and molecular characterization of disseminated tumor cells and of the prevalence and prognostic significance of the detection of MRD in patients and hematopoietic autografts. Finally, we discuss the emerging therapeutic consequences of the detection of disseminated tumor cells, with special emphasis on the therapeutic potential of antibodies. We conclude that the detection of MRD represents a hallmark for the diagnosis, monitoring, and treatment of malignant conditions in future clinical trials.

KEY WORDS: cancer, detection, disease, minimal, residual.