Initiated in the late 1950s, laboratory and clinical studies related to tumor metastasis began to alter the view of the surgical treatment of cancer. Until that time, it was generally believed that a) lymph-borne tumor cells only went to the lymph nodes, b) tumor cells in the blood lodged in the first capillary bed they encountered, and c) there was an orderly pattern of tumor cell dissemination dictated by temporal and mechanical considerations. Conversely, findings from studies reported in 1966 showed that the blood and lymphatic systems are interrelated routes of tumor cell dissemination, (top panel ). With the use of labeled tumor cells, it was shown that most cells that gained access to an organ via the bloodstream traversed that organ. Thus, it was concluded that patterns of tumor spread were not dictated solely by anatomical considerations but were also influenced by intrinsic factors in tumor cells and in the organs they accessed. The prevailing thesis of an orderly pattern of tumor cell dissemination was no longer tenable. Findings first reported in 1959 showed the existence of dormant tumor cells (bottom panel ), which were capable of unfettered growth as long as conditions were favorable, and perturbation of the host by a variety of means could produce lethal metastases from those cells. These and other findings resulted in the formulation of a new hypothesis, in 1968, whose tenets were biological in concept. That thesis was confirmed in prospective randomized clinical trials and resulted in a new paradigm for the surgical treatment of cancer.

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