Neoadjuvant therapy: theoretical, biological and medical consideration

Neoadjuvant therapy (NAT) is widely utilized in the routine management of cancer patients and various clinical trials for the treatment of breast, ovarian, rectal, esophageal, head and neck, lung, prostate and many other cancer types. There is a number of potential benefits of applying systemic treatment before the operation. NAT may significantly reduce the tumor burden thus allowing less traumatic surgery. NAT is often considered as personalized in vivo drug sensitivity test, as it allows rapid evaluation of tumor response to a given therapy and consequent adjustment of further treatment planning. NAT is an invaluable tool for in-human testing of novel therapeutic compounds, as it deals with yet chemonaive patients and permits pathological and molecular analysis of treatment-exposed tumor tissues. There are also some arguments against the use of NAT. The delay of surgery may increase the chances for metastatic tumor spread. NAT often results in the selection of treatment-resistant tumor clones, which cannot be eliminated by subsequent adjuvant therapy. NAT is likely to compromise visual inspection of surgical wound, as it reduces the size of tumor lumps and makes them invisible for the operating physician. Animal models cannot fully recapitulate the complexity of human cancer biology, the sophistication of modern surgical interventions, and the spectrum of tumor drug sensitivity in neoadjuvant and adjuvant settings. Therefore, studies on the rationale for NAT are largely limited to human studies.