Ann Coloproctol.  2023 Aug;39(4):289-300. 10.3393/ac.2022.00920.0131.

Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials

• Sychev S
• Ponomarenko A
• Chernyshov S
• Alekseev M
• Mamedli Z
• Kuzmichev D
• Polynovskiy A
• Rybakov E

• KMID: 2545299
• DOI: http://doi.org/10.3393/ac.2022.00920.0131

Abstract

Purpose
To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT).
Methods
A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867).
Results
Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50–54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50–54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50–54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06–2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25–2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26–5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes.
Conclusion
The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.

Keyword

Total neoadjuvant therapy; Rectal neoplasms; Neoadjuvant therapy; Colorectal disease; Network meta-analysis