The rationale for the use of preoperative chemotherapy.

A considerable amount of experimental and clinical data support the idea that there is a strong relationship between tumor mass and potential curability by chemotherapy. Malignancies for which there could be no realistic expectation of cure when treated at the advanced stage, may be quite sensitive to cure if the treatment can be initiated at a time when the tumor burden is very small. The somatic mutation model of drug resistance and cancer chemotherapeutic effect predicts a steep relationship between tumor burden and curability. One clinical implication of such a relationship is that the time period over which a significant proportion of individual cases would move from a position of curability to incurability may be substantially shorter than what one would intuitively expect. This argues for the earliest feasible utilization of appropriate chemotherapy as part of adjuvant treatment programs. This introduces a component of urgency into establishing a correct diagnosis and commencing appropriate anticancer drug treatment. Such measures may have the potential for increasing cure rates in a variety of human solid tumors for which adjuvant chemotherapy is deemed an appropriate technique. With the demonstration of the relative safety of such approaches then many of the ethical concerns about the early use of chemotherapy can be assuaged. One of the attractions of the method of preoperative chemotherapy is that it offers the possibility of improving cure rates in a variety of common human malignancies without developing new classes of antineoplastic drug or entirely novel treatment approaches. The prompt institution of chemotherapy during the perioperative period may have greater impact on the natural history of the disease than much more aggressive and complex treatment utilized in the later stages.