Adjuvant FLOT provides survival benefit for oesophagogastric junction and gastric adenocarcinoma patients with low tumour regression after neoadjuvant chemotherapy

Int J Cancer. 2025 Dec 15;157(12):2558-2568. doi: 10.1002/ijc.70048. Epub 2025 Jul 22.

Abstract

Oesophagogastric junction and gastric adenocarcinoma (OGA) are associated with high mortality rates, with 5-year survival rates below 50% in the curative setting. This study evaluates the efficacy of adjuvant chemotherapy (a chemotherapy regimen consisting of docetaxel, oxaliplatin, leucovorin and 5-fluorouracil [FLOT]) in patients with low tumour regression grades (TRG) following neoadjuvant FLOT (>10% viable tumour cells in surgical specimen, TRG 2/3 analogue Becker's classification). Data from all patients who had undergone ≥3 cycles of neoadjuvant FLOT with R0 resection and TRG 2/3 in surgical specimen, diagnosed between 2017 and 2020 at the University of Cologne (n = 134), were analyzed. Patients were categorised into three groups based on the administration of postoperative FLOT: 'FLOT complete' (four cycles), 'FLOT incomplete' (one to three cycles) and 'no FLOT' (0 cycles). Progression-free survival (PFS) and overall survival (OS) were compared. There is a statistically significant PFS advantage for the 'FLOT complete' group compared to 'no FLOT' (p = .028) in the total patient cohort and a tendency for an OS benefit. In the subgroup of patients with lymph node metastasis in surgical specimen (ypN+ cohort, n = 91), the PFS advantage of 'FLOT complete' was diminished and statistically no longer significant, and there is no OS benefit for these patients. However, multivariate analysis confirmed a significant PFS benefit for 'FLOT complete' both in the total cohort (p = .011) and in ypN+ patients (p = .018). These findings suggest that full adjuvant FLOT is beneficial even for OGA patients with low tumour regression; however, its efficacy appears reduced in those with lymph node metastasis, warranting further investigation into individualising treatment strategies.

Keywords: FLOT; adjuvant chemotherapy; gastric adenocarcinoma; oesophagogastric junction adenocarcinoma; tumour regression.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Chemotherapy, Adjuvant / methods
  • Docetaxel / administration & dosage
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophagogastric Junction* / drug effects
  • Esophagogastric Junction* / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Retrospective Studies
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Survival Rate

Substances

  • Leucovorin
  • Fluorouracil
  • Oxaliplatin
  • Docetaxel