Is chemoradiotherapy more effective than radiotherapy alone in patients with primary unresectable locally advanced oral cancer without distant metastases? Systematic review and meta-analysis based on the GRADE approach

This systematic review (SR) and meta-analysis aimed to evaluate the outcomes of radiotherapy (RT) alone and chemoradiotherapy (CRT) in patients with primary unresectable locally advanced oral cancer without distant metastases. Searches were performed on PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Ichushi-Web databases for articles published from inception until March 31, 2022. We selected clinical practice guidelines, SRs, and randomized controlled trials (RCTs) according to pre-established criteria. Prospective and retrospective observational clinical studies, case reports, and case series were included unless appropriate SRs or RCTs were not available. Outcomes were overall survival (OS), progression-free survival (PFS), and severe oral mucositis. We used Review Manager 5.4 software for statistical analysis and rated the certainty of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Two RCTs, with a total of 400 patients who received RT alone (205 patients) and CRT (195 patients), were eligible. The meta-analysis shows that CRT was favorably associated with OS compared with RT alone, and the certainty of the evidence was moderate. Additionally, CRT was also associated with favorable PFS compared to RT alone, and the certainty of evidence was low. Regarding side effects, CRT was associated with a higher incidence of grade ≥ 3 mucositis than RT alone, and the certainty of evidence was low. CRT was favorably associated with OS and PFS compared to RT alone in patients with primary unresectable locally advanced oral cancer without distant metastasis; however, the incidence of oral mucositis increased.