Inter-institutional heterogeneity in high-volume esophageal cancer centers: an ancillary study of JCOG1109...

Multimodal esophageal cancer treatment carries substantial perioperative risks. Although centralization has improved outcomes, variability may persist even among high-volume centers. This study aimed to evaluate inter-institutional heterogeneity in perioperative and survival outcomes using data from JCOG1109.

JCOG1109, a phase III multicenter trial, compared neoadjuvant cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin, and 5-fluorouracil (DCF); and cisplatin and 5-fluorouracil combined with radiotherapy (CF-RT) for stage IB-III esophageal squamous cell carcinoma. Individual patient data and institutional survey results were analyzed. Mixed-effects models with random intercepts and slopes, incorporating institutions as random effects, were applied to quantify heterogeneity in DCF and CF-RT's treatment effects on postoperative complications, progression-free survival (PFS), and overall survival (OS), separated from baseline institutional risks in the CF arm.

From 44 institutions, 580 patients were eligible and 546 underwent surgery. PFS treatment effect variance was smaller than baseline risk variability (CF: 0.062, standard deviation [SD]: 0.069; DCF: 0.044, SD: 0.053; CF-RT: 0.051, SD: 0.057), whereas OS variance exceeded baseline risk (CF: 0.058, SD: 0.068; DCF: 0.080, SD: 0.094; CF-RT: 0.072, SD: 0.079). Complication variance was lower in both experimental arms (CF: 0.342, SD: 0.432; DCF: 0.111, SD: 0.168; CF-RT: 0.190, SD: 0.326), although it was greater in the CF-RT arm than in the DCF arm.

Multimodal treatment was delivered with high consistency across specialized centers, as reflected by minimal heterogeneity in PFS. In contrast, moderate heterogeneity in OS indicated institutional influences, particularly post-recurrence management, which should be considered in trial designs and clinical practice.