Survival outcomes and time toxicity of Sandwich versus Sequential chemoradiation in Stage III endometrial cancer: A real-world study stratified by molecular classification
To evaluate the survival outcomes of Sandwich (Chemo-RT-Chemo) versus Sequential (Chemo-RT) therapy in Stage III endometrial cancer, focusing on the interplay between treatment intervals, time toxicity, and molecular classification. We analyzed 119 patients with Stage III EC (2015-2025) receiving either Sequential (n = 42) or Sandwich (n = 77) regimens. Endpoints included overall survival (OS), progression-free survival (PFS), relative dose intensity (RDI), and overall treatment time (OTT). Outcomes were stratified by p53 and MMR status. Among 119 patients (42 Sequential, 77 Sandwich) with well-balanced characteristics, no significant differences were observed in OS (P = .73) or PFS (P = .93). However, subgroup analysis favored the Sandwich regimen in pMMR tumors (PFS benefit, P = .026) and p53-mutant tumors (improved time-to-recurrence, P = .034). Regarding time toxicity, the Sandwich cohort demonstrated significantly shorter median overall treatment time (198.0 vs. 223.0 days; P < .001) and earlier radiotherapy initiation (77.0 vs. 171.5 days; P < .001). Chemotherapy dose intensity remained comparable (P = .878). While low-grade diarrhea was more frequent in the Sandwich arm (43% vs. 21%; P = .027), grade≧3 adverse events were rare and similar between groups. The Sandwich regimen offers a dual advantage: it reduces patient time toxicity and ensures earlier pelvic control without sacrificing chemotherapy intensity. This optimized temporal sequencing appears particularly beneficial for high-risk molecular subtypes (p53-mutant/pMMR) and supports the paradigm of molecular-directed adjuvant therapy.