Rethinking TNT in Rectal Cancer: J Clin Oncol March 26

Introduction

Total neoadjuvant therapy (TNT) has become a major advance in locally advanced rectal cancer, helping improve systemic control, increase tumor response, and expand the possibility of organ preservation. However, most trials and guidelines still treat rectal cancer as a single disease entity. This review argues that this is an oversimplification. Tumor location matters, especially when comparing mid-rectal and low-rectal cancers, because anatomy, lymphatic drainage, surgical difficulty, functional impact, and treatment goals differ substantially.

Summary

This review highlights that low-rectal cancers and mid-rectal cancers should be approached as distinct clinical entities rather than managed uniformly.

Low-rectal tumors, particularly those within 1 cm of the anal ring, present special challenges. They have more complex local anatomy, more difficult lymphatic patterns, a higher risk of positive circumferential margins, and major implications for continence, sphincter preservation, and quality of life. In these tumors, a more intensive TNT strategy may be justified, especially when the goal is organ or sphincter preservation.

In contrast, mid-rectal tumors are often more straightforward surgically, with a better chance of standard resection and preservation of function. For these cancers, the review suggests that treatment de-escalation, particularly regarding radiotherapy, may be reasonable in selected patients.

Drawing on data from more than 80 studies and trials, the authors propose a location-specific, patient-centred strategy:

De-escalate treatment in selected mid-rectal cancers

Intensify or optimise TNT in low-rectal cancers when preservation is a priority

Take-home message

The key disruptive idea is simple: rectal cancer is not one disease anatomically or functionally. Future TNT strategies should be tailored by tumor height, oncologic risk, and patient priorities, not applied uniformly.