Technical aspects of minimal residual disease detection in carcinoma patients.

Abstract

The burden of occult malignant cells which remains after a course of treatment that has resulted in clinical remission is referred to as minimal residual disease (MRD). MRD is increasingly considered as a determinant of local or systemic recurrence in cancer patients. During the last 20 years, methods for the detection of rare cancer cells have evolved from mere cytomorphological investigations to a variety of immunological and molecular assays. Since surgical therapy remains the best treatment option for cancer patients with resectable tumors, the first question to address is whether the removal of the tumor was complete or some cancer cells remained from the tumor at the primary site. Several tumor-associated DNA alterations have been identified to solve this diagnostic problem. Assays detecting tumor-associated DNA alterations have been applied to resection margins and body fluids such as bronchoalveolar lavage, sputum, urine, pancreatic juice, colonic lavage, and stool. Due to the higher sensitivity of immunocytochemical and reverse-transcriptase polymerase chain reaction (RT-PCR)-based assays, the second question to be addressed is whether systemic hematogenous or lymphatic spread of cancer cells occurred. Disseminated cancer cells have been detected in bone marrow aspirates, peripheral blood, and lymph node biopsies, and cancer cell dissemination is regarded as a relevant and independent prognostic factor. Thus, sensitive techniques for the detection of MRD are likely to guide indications for surgical or adjuvant therapy protocols in clinical oncology. However, since many of the assays for the detection of MRD are complex, and results are influenced by a variety of technical aspects, the majority of diagnostic applications have not yet been sufficiently standardized. Consequently, quality control and reproducibility of minimal disease detection assays remain unsolved problems. Therefore, well controlled collaborative studies are urgently required to evaluate indications and diagnostic standards for these assays. This review summarizes technical aspects and their implications for the clinical application of presently available assays for MRD detection in carcinoma patients.