Early spread of tumor cells is usually undetected even by high-resolution imaging technologies, preventing potentially effective early intervention. However, sensitive immunocytochemical and molecular assays now enable the specific detection of “occult” metastatic tumor cells even at the single-cell stage. These technologies provide the potential to track systemic tumor cell dissemination in the blood and the bone marrow (BM) as one of the first crucial steps in the metastatic cascade.

In colorectal cancer, approximately 50 percent of patients undergoing a curative resection (R0) die from metastatic disease within five years. Even among lymph node–negative (N0) patients, the relapse rate is 30 percent [1, 2]. In lung cancer, the prognosis is even worse, with 60 percent of R0 and 40 percent of N0 patients dying of the disease [3]. Whereas in breast and prostate cancer the overall survival today is relatively high (5 years, 80%–90%; 10 years, 70%–80%), a considerable fraction of node-negative patients still relapse (25%–30% and 15%–50%, respectively) and this can often take place many years (>10 years) after the removal of the primary tumor [4–6].

Various clinical studies have provided evidence for an association between the presence of disseminated tumor cells (DTCs) detected at the time of initial tumor resection and postoperative metastatic relapse in patients with cancers of the breast, prostate, lung, and gastrointestinal tract [7]. This work paved the way for the introduction of DTCs in international tumor staging systems [8, 9], and in 2007 DTCs and CTCs (circulating tumor cells) were mentioned for the first time in the American Society of Clinical Oncology (ASCO) recommendations on tumor markers [10].