A Meta-analysis of Total Neoadjuvant Therapies Combining Chemoradiotherapy with Induction or Consolidated Chemotherapy for Locally Advanced Rectal Cancer

Objective Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. Method In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. Results Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09-2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37-2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71-1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52-1.85), rates of R0 resection (RR 0.74; 95% CI 0.55-1.10), compliance (RR 0.52; 95% CI 0.12-2.26), and grade 3--4 toxicities (RR 0.78; 95% CI 0.57-1.06) were all similar between the two groups. Conclusion In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3-4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation.