Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

The first principle of solid tumor oncology in the curative setting is to establish local and systemic control of both visible and microscopic disease. Twenty-five years ago, randomized clinical trials established the ability of both radiation therapy and chemotherapy to eliminate microscopic disease and improve cure rates after surgery. In the subsequent 25 years, the treatment of rectal cancer has evolved to include better imaging of localized and systemic disease, better surgical techniques to diminish local recurrence, better radiation techniques to improve dosing and tolerability, and more active chemotherapy regimens. Moreover, nonoperative treatment in patients with complete clinical response to preoperative therapy has become an accepted practice, particularly for patients who would have required an abdominoperineal resection or a very low anterior resection. This development has led to the movement of the standard 4 months of adjuvant (postoperative) chemotherapy to the preoperative setting, called total neoadjuvant therapy (TNT). Despite the lack of a randomized clinical trial, TNT is in the standard practice guidelines. Our colleagues in major academic centers have adopted TNT, whereas our colleagues practicing in community settings email and call us with a single question: is this ok?

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