Neoadjuvant Chemoradiation versus Perioperative Chemotherapy in Locally Advanced Resectable Esophageal Adenocarcinoma: A National Analysis.

OBJECTIVE: There is ongoing debate regarding the optimal multimodal treatment for patients with resectable locally advanced esophageal adenocarcinoma, with the recent ESOPEC trial suggesting perioperative chemotherapy to yield superior survival compared to CROSS neoadjuvant chemoradiation. Providing a contemporary perspective, we sought to elucidate survival outcomes among a national cohort. METHODS: We performed a retrospective analysis of all clinically staged T1N+M0 or T2-4aN+/-M0 esophageal adenocarcinoma patients ≥18years within the 2016-2023 National Cancer Database. Only patients who underwent esophagectomy were considered. Those who received neoadjuvant chemotherapy and ≥41.4Gy radiation were grouped as Neoadjuvant-CR, while patients treated with perioperative multi-agent chemotherapy were considered Perioperative-Chemo. RESULTS: Of 7,387 esophagectomy patients, 462(6%) received Perioperative-Chemo and 6,925(94%) Neoadjuvant-CR. On average, and relative to Neoadjuvant-CR, Perioperative-Chemo was incrementally younger, but of similar sex, CDI, and mean tumor size. Overall survival at five years was 49% for Perioperative-Chemo and 42% for Neoadjuvant-CR. Following risk adjustment, and relative to receipt of neoadjuvant chemoradiation, treatment with perioperative chemotherapy was linked with improved survival at one (Hazard Ratio[HR] 0.66, 95% Confidence Interval[CI] 0.48-0.90), three (HR 0.76, CI 0.62-0.93), and five years (HR 0.80, CI 0.66-0.97). Restricted Mean Survival Time analysis quantified the survival benefit of perioperative chemotherapy at 3.7 months (CI 0.01-7.5). CONCLUSIONS: Among patients who underwent esophagectomy, treatment with perioperative chemotherapy was linked with superior survival over five years, relative to neoadjuvant chemoradiotherapy. Our work supports the early findings of the ESOPEC trial and suggests perioperative chemotherapy should be considered upfront in the multimodal treatment of these complex patients.