Definitive non-surgical management of locally advanced esophageal adenocarcinoma: A systematic review and meta-analysis.

e16143 Background: For patients with Locally Advanced Esophageal Adenocarcinoma (LAEA), esophagectomy with perioperative chemo-radiation is the preferred treatment. Esophagectomy, however, is associated with substantial morbidity, with postoperative complication rates approaching 60%. Organ-preserving, esophagectomy-free approaches may reduce treatment-related morbidity but carry a risk of locoregional recurrence. This meta-analysis evaluates the efficacy and safety of esophagectomy-free treatment approaches for LAEA. Methods: A comprehensive PRISMA-guided systematic literature search was conducted across PubMed, Cochrane, and Embase, yielding 8 clinical trials evaluating non-surgical treatment strategies in patients with LAEA. Data were extracted, and outcomes were pooled using inverse-variance meta-analysis with logit transformation under random-effects models, with heterogeneity quantified by I² in the R statistical package version 4.4.0. Results: A total of 945 patients were included, of whom 76% were male and 24% female, with a median age of 65.5 (58-72) years. Patients had non-metastatic locally advanced stage II–III disease and good baseline functional status (ECOG/WHO/Zubrod 0–1). Patients were treated with cetuximab plus chemoradiation (CRT) = 413, CRT with weekly carboplatin+paclitaxel = 129, induction chemotherapy (IC) + CRT = 51, pembrolizumab plus CRT = 40, XELOX followed by CRT = 19, IC + radiotherapy (RT) = 17, definitive CRT = 12, definitive RT = 8, and celecoxib plus CRT = 7. The median follow-up period was 22.3 (16-46) months. The pooled complete response rate was 41% (95% CI, 24–60%; I² = 93.3%), and the pooled overall response rate was 42% (95% CI, 32–53%). Pooled 2-and 3-year overall survival rates were 45% (95% CI, 40-49%) and 36% (95% CI, 29-45%; I² = 75.7%), respectively. Median OS was 19.3 (16-47) months. The pooled 2-year PFS was 32% (95% CI, 7-74%; I² = 82.2%), with a median PFS of 11.8 (8.8-24.1) months. Pooled rates of locoregional and distant progression were 41% (95% CI, 33–49%; I² = 65.7%) and 36% (95% CI, 25–48%; I² = 79.1%), respectively. Treatment-related adverse events were variably reported; common grade ≥3 toxicities included hematologic events, pneumonitis, esophagitis, dysphagia, diarrhea, fatigue, and dehydration. The pooled incidence of grade 3–4 neutropenia was 12% (95% CI, 6–22%; I² = 72.5%). Conclusions: Esophagectomy-free treatment strategies demonstrate meaningful clinical activity with acceptable toxicity in selected patients with LAEA. These approaches may offer a viable organ-preserving alternative to standard therapy. Prospective randomized trials are needed to better define patient selection, optimize surveillance strategies, and compare long-term outcomes with surgical approaches.