Postoperative radiotherapy for resected esophageal squamous cell carcinoma: a systematic review and meta-analysis

The role of postoperative radiotherapy (PORT) in patients with radically resected esophageal squamous cell carcinoma (ESCC) remains controversial. This meta-analysis aimed to evaluate the efficacy of PORT compared with surgery alone in terms of survival outcomes and toxicity.

A systematic search was performed in PubMed, EMBASE, and the Cochrane Library from January 1990 to June 2025 for randomized controlled trials (RCTs) and retrospective studies (RSs) comparing PORT versus surgery alone in ESCC patients who underwent curative resection. Primary outcomes were overall survival (OS) and disease-free survival (DFS), reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes included locoregional recurrence (LRR), distant metastasis (DM), and treatment toxicity. Quality was assessed using the revised Cochrane risk-of-bias tool (ROB2) for RCTs and the Newcastle-Ottawa Scale (NOS) for retrospective studies. The Jadad scale was also applied for consistency with previous meta-analyses. Meta-regression and subgroup analyses were performed to explore heterogeneity.

Thirty-five studies (8 RCTs, 27 RSs) comprising 11,385 patients (4,968 in the PORT group, 6,417 in the surgery alone group) were included. PORT significantly improved OS (HR = 0.74, 95% CI: 0.69-0.80, P < 0.001, I² = 67%) and DFS (HR = 0.62, 95% CI: 0.58-0.67, P < 0.001, I² = 47%) compared with surgery alone. PORT significantly reduced LRR (OR = 0.30, 95% CI: 0.27-0.34, P < 0.001, I² = 0%) but had no effect on DM (OR = 1.01, 95% CI: 0.92-1.11, P = 0.85, I² = 0%). Subgroup analyses showed that PORT improved OS in patients with positive lymph nodes (HR = 0.65), T3-4 stage (HR = 0.72), R0 resection (HR = 0.72), and those receiving modern radiotherapy (3D-CRT/IMRT, HR = 0.67). The addition of chemotherapy yielded the greatest OS benefit (HR = 0.55). PORT was associated with a significantly higher incidence of grade ≥3 acute toxicity (OR = 2.45, 95% CI: 1.89-3.18, P < 0.001), mainly radiation esophagitis (12.5%) and leukopenia (15.2%), but grade ≥4 toxicity was rare (<5%).

For patients with radically resected ESCC, PORT significantly improves OS and DFS and reduces LRR, especially in those with high-risk features. A radiation dose of 50 Gy is recommended to achieve optimal benefit. Although PORT increases acute toxicity, it is generally manageable.

https://www.crd.york.ac.uk/PROSPERO/search, Identifier CRD420261400043.