The emerging role of neoadjuvant chemotherapy for rectal cancer.

Locally advanced rectal cancer remains a substantial public health problem. Historically, the disease has been plagued by high rates of both distant and local recurrences. The standardization of pre-operative chemoradiation and transmesorectal excision (TME) have greatly lowered the rates of local recurrence. Efforts to improve treatment through use of more effective radiosensitizing therapies have proven unsuccessful in rectal cancer. Presently, due to improved local therapies, distal recurrences represent the dominant problem in this disease. Adjuvant chemotherapy is currently of established benefit in colorectal cancer. As such, adjuvant chemotherapy, consisting of fluoropyrimidine and oxaliplatin, represent the standard of care for many patients. However, after pre-operative chemoradiotherapy and rectal surgery, the administration of highly effective chemotherapy regimens has proven difficult. For this reason, novel neoadjuvant approaches represent appealing avenues for investigation. Strategies of neoadjuvant chemotherapy alone, neoadjuvant chemotherapy followed by chemoradiation and neoadjuvant chemoradiation followed by chemotherapy are under investigation. Initial encouraging results have been noted, though definitive phase III data is lacking.