Abstract
BACKGROUND: Optimal multimodal treatment for esophagogastric junction adenocarcinoma remains debated. While the ESOPEC trial supports perioperative FLOT, real-world evidence is limited, particularly for Siewert type II tumors. AIM: To compare survival and treatment outcomes of perioperative FLOT versus definitive-dose chemoradiotherapy in non-metastatic Siewert II esophagogastric junction adenocarcinoma. METHODS: Siewert type II esophagogastric junction adenocarcinoma was defined as tumors with an epicenter located between 1 cm above and 2 cm below the esophagogastric junction. We retrospectively identified patients with non-metastatic Siewert type II esophagogastric junction adenocarcinoma treated between January 2015 and December 2024 at three tertiary cancer centers. Patients received either perioperative FLOT chemotherapy or concurrent chemoradiotherapy with weekly carboplatin-paclitaxel and 50.4 Gy radiotherapy, delivered as definitive therapy or neoadjuvantly prior to planned surgery. Clinical characteristics, treatment delivery, pathological response, survival outcomes, and treatment-related toxicities were analyzed. RESULTS: Seventy patients were included (FLOT, n=50; concurrent chemoradiotherapy, n=20). Surgery was performed in 45/50 (90%) FLOT patients and 7/20 (35%) concurrent chemoradiotherapy patients, representing a major difference between treatment groups. Median follow-up was 53.7 months. Median overall survival was 43.0 months in the FLOT group and 48.6 months in the concurrent chemoradiotherapy group (p=0.498). Median event-free survival was 34.2 months and 35.0 months, respectively (p=0.548). No pathological complete response occurred in the FLOT group; one patient (14.3%) in the concurrent chemoradiotherapy group achieved pathological complete response. Grade 3-4 toxicities were more frequent with FLOT (26% vs. 5%). Distant relapse was the predominant recurrence pattern in both groups. CONCLUSION: Despite a substantial difference in surgical resection rates between groups, perioperative FLOT and concurrent chemoradiotherapy showed comparable survival outcomes in this real-world cohort of patients with Siewert type II EGJ adenocarcinoma. These findings should be interpreted with caution, as treatment selection and baseline differences may have influenced outcomes. Treatment decisions should be individualized based on patient characteristics and clinical context.