Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials

Abstract

Background This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). Methods A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. Results In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. Conclusion This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Surgical Outcomes in Total Neoadjuvant Therapy for Rectal Cancer versus Standard Long Course Chemoradiation

“…Some authors have previously attributed the oncological benefits of TNT to better chemotherapy compliance 37 as poor compliance may be the reason for distant failure in the management of rectal cancer 38,39 . A recent network meta-analysis showed no difference in compliance to chemotherapy whatever the neoadjuvant treatment regimen 40 was—and this is further evidence for the efficacy of TNT as it provides improved disease-free survival without any difference in compliance.…”

A contemporary assessment of total neoadjuvant therapy (TNT) protocols for locally advanced rectal cancer: adoption and expert perspectives at German Cancer Society (DKG)-certified colorectal cancer centers

“…Total neoadjuvant therapy is a novel approach for locally advanced rectal cancer. Emerging data from TNT studies demonstrate higher rates of pathological complete response (pCR), potential benefits in terms of distant metastasis control, and disease-free survival (DFS) (Donnelly et al 2023 ; Sclafani et al 2021 ; Goffredo et al 2022 ). However, the optimal sequence of treatments remains a contentious subject, and to date, no proven survival benefit (OS) has been demonstrated.…”

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study

“…For patients with intermediate risk rectal tumors, defined as cT3c-dN0M0 or cT1-3N1M0 mesorectal fascia clear (MRF-), the recommended treatment strategy in Northern Europe is short-course radiotherapy (SCRT; 25 Gray (Gy) in five fractions) followed by (delayed) tumor resection [1] , [2] , [3] . SCRT is also used in patients not eligible for tumor resection to provide palliation of symptoms, in elderly not eligible for chemoradiation, in combination with chemotherapy to treat locally advanced rectal cancer (LARC), for early tumors to allow organ-preservation, and in combination with chemotherapy, immunotherapy and metastasectomy for the treatment of metastatic rectal cancer [1] , [2] , [3] , [4] , [5] .…”