Beyond Pathological Complete Response: Long-term Outcomes in Esophageal and Esophagogastric Junction Adenocarcinoma After Multimodal Therapy—A Systematic Review and Individual Patient-Data Meta-Analysis

BACKGROUND: Neoadjuvant chemotherapy (nCT) for esophageal and esophagogastric junction (EGJ) adenocarcinoma is associated with better survival but worse pathological complete response (pCR) rate as compared with neoadjuvant chemoradiotherapy (nCRT). The aim of the present study is to compare long-term outcomes in patients with esophageal or EGJ adenocarcinoma and pCR after nCT or nCRT. PATIENTS AND METHODS: A systematic review of the literature in PubMed, Embase and web sources was performed up to November 2025. Studies comparing nCT and nCRT in patients with esophageal or EGJ adenocarcinoma and pCR were identified. An individual patient-data (IPD) meta-analysis was performed for overall survival (OS) and disease-free survival (DFS). RESULTS: Overall, 1454 patients from six different studies were included (374 in nCT group and 1080 in nCRT group). 1-, 3-, and 5-year OS was superior in the nCT group as compared with nCRT group, being 95.4% versus 87.8%, 81.5% versus 64.8% and 73.8% versus 56%, respectively (p < 0.001). Analogously, superior DFS was observed for the nCT group at one, three and 5 years (p < 0.001). In the one-stage meta-analysis nCT was associated with decreased risk of death (HR = 0.49, p < 0.001) and recurrence (HR = 0.24, p