Total neoadjuvant therapy for locally advanced rectal cancer A meaningful treatment option?

Background Since neoadjuvant chemoradiotherapy was implemented for locally advanced rectal cancer, the local recurrence rate has been markedly reduced but the rate of distant metastases has not changed at 25-30%. Total neoadjuvant therapy (TNT), i.e. the augmentation of neoadjuvant chemo(radio)therapy by preoperative systemic therapy, aims to reduce the rate of distant metastasis and improve disease-free survival. Objective This article summarizes the current relevant randomized trials regarding TNT and discusses the indications, best sequence of therapy and optimal therapeutic regimen. Material and methods A literature search was conducted with the terms total neoadjuvant therapy, randomized trial, pathologic complete response and disease-free survival. Results The RAPIDO trial showed an advantage of TNT vs. long-term chemoradiotherapy with respect to its primary endpoint of disease-related treatment failure after 3 years. The PRODIGE 23 study showed that TNT was superior to long-term chemoradiotherapy in disease-free survival after 3 years. The OPRA study compared two different regimens for TNT and found consolidation chemotherapy to be superior to induction chemotherapy in the endpoint of organ preservation after 3 years. Discussion The use of TNT for locally advanced rectal cancer of the lower and middle third improves oncological results and is the preferred treatment option for patients in good performance status with far advanced rectal cancer (cT4, extramural vascular invasion, EMVI positive, lateral lymph nodes positive, circumferential resection margin, CRM positive).

Automated summary

This article summarizes the current randomized trials on total neoadjuvant therapy (TNT) for locally advanced rectal cancer and discusses the indications, optimal sequence of therapy, and therapeutic regimen. The findings suggest that TNT can improve oncological outcomes in patients with lower and middle third rectal cancer and is the preferred treatment option for certain patients.