Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study
- Author(s)
- SPACE-FLOT Investigators;
- Details
- Publication Year 2025,Volume 112,Issue #4,Page znaf056
- Journal Title
- British Journal of Surgery
- Publication Type
- Research article
- Abstract
- Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use.Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan–Meier, Cox regression, propensity score matched, and sensitivity analysis.A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0–39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit.Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.Chemotherapy for cancers of the stomach and oesophagus is associated with significant side effects. Being able to predict which patients may benefit or not from further chemotherapy after surgery may optimize its use and reduce harm. In this international study of real-world patients with stomach and oesophageal cancer undergoing surgery and chemotherapy, the authors found that only patients with a partial response to pre-surgery chemotherapy benefited from further chemotherapy after surgery. Patients with a minimal response or no response to pre-surgery chemotherapy, or those whose cancer had been eradicated by pre-surgery chemotherapy, did not benefit from further chemotherapy after surgery. This study suggests that a tumour’s response to pre-surgery chemotherapy may guide the use of chemotherapy after surgery.
- Publisher
- Oxford University Press
- Department(s)
- Surgical Oncology
- Publisher's Version
- https://doi.org/10.1093/bjs/znaf056
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- Refer to copyright notice on published article.
Creation Date: 2026-01-15 05:58:37
Last Modified: 2026-01-15 05:58:45