Network meta-analysis of RTCs for efficacy of neoadjuvant treatment in rectal cancer

Abstract

Background

This network meta-analysis examined the efficacy of different types of neoadjuvant therapy (NAT) for rectal cancer in improving clinical and pathologic outcomes.

Methods

PRISMA-compliant systematic review of PubMed and Scopus including only randomized clinical trials comparing two or more NAT regimens for rectal cancer. A network meta-analysis was undertaken for the main outcomes, including pathological complete response (pCR), disease downstaging, R0 resection, permanent stoma, and major adverse effects. Risk of bias was assessed using the ROB-2 tool.

Results

19 randomized controlled trials incorporating 7037 patients (62 % males) were included in the analysis. Compared to standard neoadjuvant chemoradiation (NCRT), consolidation total neoadjuvant therapy (TNT) (OR: 1.82, 95 % CI: 1.46–2.27; p < 0.001) and induction TNT (OR: 1.72, 95 % CI: 1.31–2.26; p < 0.001) had higher odds of achieving pCR. Induction TNT was also significantly associated with higher odds of major adverse effects than was NCRT (OR: 3.14, 95 % CI: 2.50–3.94; p < 0.0001). Compared to NCRT, long course chemotherapy significantly increased the odds of R0 resection (OR: 1.42, 95 % CI: 1.13–1.78; p = 0.002), while consolidation TNT significantly increased organ preservation rates (OR: 2.82, 95 % CI: 1.58–5.05; p < 0.001). Short course radiotherapy doubled the odds of positive circumferential resection margins (CRM) compared to NCRT (OR: 1.99, 95 % CI: 1.11–3.55; p = 0.02).

Conclusions

Consolidation and induction TNT were superior in achieving better pathological outcomes in rectal cancer, offering significant benefits over standard NCRT. However, they were associated with a higher risk of adverse effects. Conversely, short course radiotherapy was linked to higher rates of positive CRM.