Efficacy and safety of radiotherapy in first-line treatment for de novo advanced esophageal cancer in the era of immunochemotherapy: a systematic review and meta-analysis.

[PURPOSE] To evaluate the efficacy and safety of systemic treatment combined with radiotherapy (RT) as the first-line treatment for de novo advanced esophageal cancer (EC).

[METHODS] A meta-analysis was conducted, and it followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A literature search was performed systematically in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2025. The protocol of this meta-analysis was published in PROSPERO with the registration number CRD42025650118.

[RESULTS] Eight studies involving a total of 11,356 patients were finally included. Systemic treatment combined with RT improved OS (HR = 0.72, 95% CI: 0.70-0.74, P < 0.001) and PFS (HR = 0.70, 95% CI: 0.62-0.78, P < 0.001) compared with systemic treatment alone. The grade ≥ 3 treatment-related lymphopenia (OR = 5.52, P < 0.001), leukopenia (OR = 1.56, P < 0.001), and esophagitis (OR = 13.11, P < 0.001) were more frequent in the RT-combined group; no significant differences were observed in other severe toxicities. Subgroup analysis on systemic treatment type, ESCC, and TNM stage edition also demonstrated that this RT-combined treatment could provide significant survival benefits. Exploratory analysis showed that maximal survival benefit emerged in patients who received systemic therapy, especially immunochemotherapy, combined with radical (≥ 50 Gy) primary tumor RT.

[CONCLUSIONS] By synthesizing data from both the pre-immunotherapy and immunotherapy eras involving 11,356 patients, we found that the incorporation of radical radiotherapy into first-line systemic treatment regimens improves survival outcomes while maintaining acceptable toxicity profiles in selected patients with advanced EC.Further randomized clinical trials are needed to verify our conclusions.