Total neoadjuvant therapy for rectal cancer.

While outcomes for patients with locally advanced disease have improved considerably with combined modality therapy, there is now an emphasis on developing risk-adapted treatment strategies. Moreover, the primary cause of death from locally advanced rectal cancer is related to distant progression, which now exceeds the rate of local failure. Thus, the necessity to optimally address micrometastatic disease has led to increasing interest in delivering chemotherapy in the neoadjuvant setting rather than in the postoperative setting. This review critically appraises the emerging literature on the options for sequencing of therapy, focusing on the total neoadjuvant therapy paradigm as well as emerging options for omitting components of multimodality therapy.