Patterns of recurrence after perioperative FLOT for resectable gastric cancer: A systematic review and meta-analysis.

Abstract

e16094 Background: Despite curative-intent resection and perioperative chemotherapy, gastric and gastroesophageal cancer (GC/GEJ) remains an aggressive malignancy with high rates of disease recurrence. Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the current standard of care and improves survival outcomes; however, detailed anatomic patterns of recurrence in the FLOT era remain incompletely characterized. Improved understanding of site-specific recurrence may inform surveillance strategies and guide the development of rational systemic and locoregional therapies. Methods: We performed a systematic review and meta-analysis of three studies (one prospective randomized trial [ESOPEC] and three retrospective cohorts) reporting anatomic patterns of recurrence in patients with GC/GEJ treated with perioperative FLOT. Site-specific recurrence risks were pooled using random-effects meta-analysis of proportions with 95% confidence intervals (CI). Outcomes included peritoneal/pleural, liver, lung, lymph node, bone, brain, other distant, and isolated local recurrence. Between-study heterogeneity was assessed using the I² statistic. Results: Four studies encompassing 329 patients with documented recurrence were included. Distant recurrence was the predominant pattern, with the highest pooled recurrence risk was observed in the peritoneal/pleural cavity (0.13; 95% CI, 0.09–0.18; I² = 81%), followed by lymph node recurrence (0.07; 95% CI, 0.03–0.16; I² = 90%) and liver metastases (0.08; 95% CI, 0.05–0.12; I² = 69%). Lung metastases were less frequent (0.04; 95% CI, 0.03–0.06; I² = 0%). Brain (0.02; 95% CI, 0.01–0.04; I² = 4%), bone (0.03; 95% CI, 0.01–0.05), and other distant sites (0.03; 95% CI, 0.01–0.05; I² = 62%) were uncommon. Isolated local-only recurrence remained infrequent (0.05; 95% CI, 0.03–0.10; I² = 78%). Conclusions: In the contemporary FLOT era, recurrence after curative-intent resection of GC/GEJ cancer is predominantly systemic, with the highest absolute risk observed in the peritoneal/pleural compartment. Liver and nodal metastases represent the next most frequent failure sites, whereas isolated local recurrence remains less common. These findings indicate that most recurrences after treatment arise from occult systemic or peritoneal disease rather than from inadequate local control, and support prioritizing improved biomarker-driven systemic and peritoneal-directed strategies in future clinical trials over intensification of local therapy alone. Peritoneal-directed approaches remain investigational, and optimized systemic control represents the principal unmet need in resectable GC/GEJ cancer.