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. 2020 Dec 5;12(12):3655.
doi: 10.3390/cancers12123655.

Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

Maria C Riesco-Martinez  1   2 , Carlos Fernandez-Martos  3 , Cristina Gravalos-Castro  1 , Paula Espinosa-Olarte  1   2 , Anna La Salvia  1   2 , Luis Robles-Diaz  1 , Andrea Modrego-Sanchez  1 , Rocio Garcia-Carbonero  1   2
Affiliations

Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

Maria C Riesco-Martinez et al. Cancers (Basel). .

Abstract

Multimodality treatment is a standard of care for LARC, but the optimal sequencing of the treatment modalities remains unclear. Several randomized clinical trials (RCTs) compared total neoadjuvant treatment (TNT) vs. standard neoadjuvant chemoradiotherapy (CRT) with inconsistent results. A systematic review and meta-analysis was performed to evaluate the efficacy of TNT in terms of complete pathological response (pCR) rate, disease-free and overall survival vs. standard CRT in LARC. A systematic search was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and meeting abstracts up to May 2020. RCTs comparing CRT vs. TNT followed by surgery in LARC were eligible for the study. Study selection and data extraction were done following PRISMA guidelines by two independent reviewers. The Mantel-Haenzel method was used to obtain a fixed-effects model of pooled odds or hazard ratios for the main outcomes. Eight RCTs, including 2301 patients, met the eligibility criteria. TNT significantly improved pCR rate (OR = 1.99, 95% confidence interval (CI) 1.59-2.49; p < 0.001), 3-year disease-free-survival (DFS) (HR = 0.82, 95%CI 0.71-0.95; p = 0.01) and 3-year overall survival (OS) (hazard ratio (HR) = 0.81, p = 0.04). Grade 3-4 adverse events were not significantly different in both strategies (OR = 1.58; p = 0.14). An improved pCR rate was documented regardless of the type of radiotherapy administered (long vs. short fractionation schedules). No significant heterogeneity was found. The results of this meta-analysis show that TNT improves pCR and survival rates vs. standard preoperative CRT in patients with LARC. TNT may become a new standard of care in LARC, although longer follow-up is needed to properly assess its long-term impact on survival.

Keywords: chemotherapy; meta-analysis; neoadjuvant therapy; rectal cancer; treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart showing study selection.
Figure 2
Figure 2
(A) Forest plot for pathologic complete response of TNT vs. standard treatment. Forest plot for pathologic complete response of TNT vs. standard treatment using: (B) induction chemotherapy in the experimental arm; (C) consolidation chemotherapy in the experimental arm; (D) long-course chemo-radiotherapy in the experimental arm; (E) short-course radiotherapy in the experimental arm. CI: confidence interval, OR: odd ratio, TNT: total neoadjuvant therapy.
Figure 3
Figure 3
(A) Forest plot for 3-year DFS TNT vs. CRT. (B) Forest plot for 3-year OS TNT vs. CRT.
Figure 4
Figure 4
(A) Forest plot for G3–4 adverse events. (B) Forest plot for G3–4 adverse events due to surgical complications.
See this image and copyright information in PMC

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