OA02.3. Does Survival Among Patients Achieving Pathological Complete Response Differ Between FLOT and CROSS in Oesophageal Adenocarcinoma?

Abstract

Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Pathological complete response (pCR) after neoadjuvant therapy is associated with favourable prognosis in oesophageal adenocarcinoma, but whether outcomes differ according to treatment modality remains uncertain. This study compared survival among patients achieving pCR following perioperative FLOT chemotherapy versus CROSS chemoradiotherapy. This international multicentre cohort included patients with oesophageal, or Siewert I/II junctional adenocarcinoma treated between 2018 and 2024 who underwent neoadjuvant FLOT or CROSS followed by curative oesophagectomy and achieved ypT0N0. Data were derived from prospectively maintained databases across 14 European high-volume centres. Patients with squamous carcinoma, incomplete pathological response, non-curative surgery, missing key variables, or 90-day mortality were excluded. Overall survival (OS) was the primary endpoint; secondary endpoints included disease-free survival (DFS), recurrence patterns, and nodal-stage–stratified outcomes. Multivariable Cox regression adjusted for demographic, tumour, and operative factors. Kaplan–Meier methods and sensitivity analyses were performed. Of 2717 patients, 297 achieved pCR (CROSS 150; FLOT 147). FLOT patients were younger and more frequently clinically node-positive, but postoperative outcomes were similar. On unadjusted analysis, FLOT was associated with improved OS and DFS (both HR 0.32, p<0.001). After adjustment, FLOT remained independently associated with superior OS (HR 0.34, 95% CI 0.16–0.69, p=0.003) and DFS (HR 0.35, 95% CI 0.19–0.62, p<0.001). Recurrence was less frequent (8.8% vs 24.7%), Patterns differed (p<0.001): distant-only relapse predominated after CROSS (70.3%), whereas FLOT showed fewer distant-only recurrences and longer time to recurrence. cN status sub analysis also showed significant survival benefit in cN0–1 disease was and directionally consistent in cN2–3 disease in FLOT arm. This is the largest and only study that directly compares pCR Survival between FLOT and CROSS NAT. Among patients achieving pCR, FLOT was associated with improved survival and reduced recurrence compared with CROSS. These findings suggest that the prognostic significance of pCR may vary according to neoadjuvant modality and should be interpreted in the context of treatment strategy.