Multimodal treatments for resectable esophagogastric junction cancer: a systematic review and network meta-analysis

BACKGROUND: Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically. METHODS: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.). RESULTS: Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, ‘PreCRT’ (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than ‘PeriCT’ (perioperative chemotherapy; HR 1.32, P-score = 0.591) and ‘PreCT’ (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and ‘PreCRT’ was still the optimal node. CONCLUSION: Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).