Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials

Xiping Zhang; Shujie Ma; Yinyin Guo; Yang Luo; Laiyuan Li

doi:10.1371/journal.pone.0276599

Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials

PLoS One. 2022 Nov 4;17(11):e0276599. doi: 10.1371/journal.pone.0276599. eCollection 2022.

Authors

Xiping Zhang¹, Shujie Ma², Yinyin Guo³, Yang Luo⁴, Laiyuan Li⁵

Affiliations

¹ Department of General Surgery, Qinan Hospital, Tianshui, China.
² Department of General Surgery, People's Hospital of Gannan, Hezuo, China.
³ Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou, China.
⁴ Department of Neurology, The First Hospital of Lanzhou University, Lanzhou, China.
⁵ Department of Anorectal Surgery, Gansu Provincial Hospital, Lanzhou, China.

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) before total mesorectal excision (TME) and followed systemic chemotherapy is widely accepted as the standard therapy for locally advanced rectal cancer (LARC). This meta-analysis was to evaluate the current evidence regarding nCRT in combination with induction or consolidation chemotherapy for rectal cancer in terms of oncological outcomes.

Methods: A systematic search of medical databases (PubMed, EMBASE and Cochrane Library) was conducted up to the end of July 1, 2021. This meta-analysis was performed to evaluate the efficacy of TNT in terms of pathological complete remission (pCR), nCRT or surgical complications, R0 resection, local recurrence, distant metastasis, disease-free survival (DFS) and overall survival (OS) in LARC.

Results: Eight nRCTs and 7 RCTs, including 3579 patients were included in the meta-analysis. The rate of pCR was significantly higher in the TNT group than in the nCRT group, (OR 1.85, 95% CI 1.39-2.46, p < 0.0001), DFS (HR 0.80, 95% CI 0.69-0.92, p = 0.001), OS (HR 0.75, 95% CI 0.62-0.89, p = 0.002), nCRT complications (OR 1.05, 95% CI 0.77-1.44, p = 0.75), surgical complications (OR 1.02, 95% CI 0.83-1.26, p = 0.83), local recurrence (OR 1.82, 95% CI 0.95-3.49, p = 0.07), distant metastasis (OR 0.77, 95% CI 0.58-1.03, p = 0.08) did not differ significantly between the TNT and nCRT groups.

Conclusion: TNT appears to have advantages over standard therapy for LARC in terms of pCR, R0 resection, DFS, and OS, with comparable nCRT and postoperative complications, and no increase in local recurrence and distant metastasis.

Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Comparative Study
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Antineoplastic Agents* / administration & dosage
Antineoplastic Agents* / therapeutic use
Chemoradiotherapy* / methods
Humans
Mesentery / surgery
Neoadjuvant Therapy* / methods
Neoplasms, Second Primary*
Proctectomy* / methods
Rectal Neoplasms* / drug therapy
Rectal Neoplasms* / pathology
Rectal Neoplasms* / radiotherapy
Rectal Neoplasms* / surgery
Retrospective Studies
Standard of Care
Treatment Outcome

Substances

Antineoplastic Agents

Grants and funding

the Natural Science Foundation of Gansu Province (No.20JR10RA371, L.LY), Fundamental Research Funds for the Central Universities (No.lzujbky-2019-kb21 L.L.Y & No.lzujbky-2020-kb22 L.Y), and Institute Scientific Research Fund Project/Youth Project(No. 20GSSY4-8 L.L.Y). The funders (Laiyuan Li and Yang Luo) had a role in study design, data collection, analysis, the decision to publish, and preparation of the manuscript.