Management of cT2N0M0 esophageal cancer: a systematic review and meta-analysis

Management of cT2N0M0 esophageal cancer is challenging due to staging limitations and limited evidence. While neoadjuvant therapies benefit advanced disease, its role in cT2N0M0 remains unclear, compounded by underrepresentation in trials and the differing responses to treatment between adenocarcinoma (EAC) and squamous cell carcinoma (SCC). To address this, the ISDE conducted a systematic review and meta-analysis comparing outcomes of neoadjuvant therapy plus surgery (NeoAdj+S) versus primary surgical resection (PSR). MEDLINE, EMBASE, and CENTRAL were searched to 25 November 2024 for English-language studies of adults (≥18 years) with EAC or SCC staged as cT2N0M0. Case series with ≤7 patients, recurrent disease were excluded. Two independent reviewers (YE, SL) selected studies, and extracted data. A random-effects meta-analysis was performed to assess outcomes. Of 299 unique articles screened, 18 studies were included, totaling 14,566 cT2N0 patients. Pooled analysis revealed no statistically significant differences between NeoAdj+S and PSR in terms of 5-year overall survival (OS) (RR 1.08, 95% CI 0.85-1.36; favoring NeoAdj+S), 3-year OS (RR 1.10, 95% CI 0.92-1.30; favoring NeoAdj+S); 5-year disease-free survival (RR 0.88, 95% CI 0.70-1.12; favoring PSR), 30-day mortality (RR 0.91, 95% CI 0.53-1.54; favoring NeoAdj+S), overall complication rates (RR 0.97, 95% CI 0.87-1.08; favoring NeoAdj+S); surgical complications (RR 0.92, 95% CI 0.78-1.08; favoring NeoAdj+S); or medical complications (RR 0.86, 95% CI 0.61-1.23; favoring NeoAdj+S). All included studies demonstrated high risk-of-bias. No clear survival or perioperative advantage was found for NeoAdj+S over PSR. High-quality clinical trials are needed to guide treatment decisions.