Optimal choice of different neoadjuvant chemoradiotherapies for locally advanced rectal cancer: systematic review and network meta-analysis.

The objective of this study is to compare the pathological complete response (pCR) and survival rates of different neoadjuvant chemoradiotherapy modalities (NACRT) for locally advanced rectal cancer, which is defined as rectal cancer with T3-4/N + and without distant metastasis. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the Chinese Society of Clinical Oncology (CSCO) for randomized controlled trials (RCTs) and late-breaking abstracts on NACRT in locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) from inception to December 2024. Eighteen articles including 11658 MSS LARC patients were included: nine articles compared concurrent oxaliplatin or irinotecan with standard chemoradiotherapy, six articles conducted total neoadjuvant chemotherapy (cTNT), and three articles integrated immunotherapy (iTNT) as the NACRT regimen. CapOX cTNT modality ranked first to achieve the best pCR. The consolidation of two cycles of CapOX/FOLFOX cTNT ranked first in achieving the best 5-year overall survival (OS) rate. The consolidation of six cycles of FOLFOX cTNT ranked first in achieving the best 5-year disease-free survival (DFS) rate. Evidence from this network meta-analysis suggests that cTNT regimens, including CapOX cTNT and mFOLFIRINOX cTNT as induction regimens, have significant benefits in achieving the best pCR rate in MSS LARC patients. According to our network analysis, iTNT was not as beneficial as cTNT in achieving the best pCR. Consolidation of cTNT has the advantage of achieving long-term survival. Adverse events (AEs) reported for most iTNT modalities appear manageable.