Italian observational RealFLOT cohort reports long-term outcomes of perioperative FLOT in resectable gastric cancer

A long-term analysis of the multicentre, prospective observational RealFLOT study reports that perioperative FLOT chemotherapy was feasible in 307 patients with resectable gastric or gastroesophageal junction adenocarcinoma treated in Italy. With a median follow-up of 31.2 months, median disease-free survival was 25.5 months and median overall survival was 73.5 months. These findings describe outcomes in the enrolled cohort and do not establish a causal effect of treatment.

The cohort included patients receiving preoperative FLOT, comprising fluorouracil, oxaliplatin and docetaxel. Most enrolled patients had stage III disease (65.1%), a gastric primary tumour (57.0%) or non-intestinal histology (46.6%). Microsatellite instability was detected in 8.8% of cases and HER2 positivity in 13.6% of tested cases. The investigators estimated survival probabilities with the Kaplan–Meier method, compared groups using the log-rank test and calculated hazard ratios with 95% confidence intervals through Cox regression. Endpoints included disease-free survival, overall survival, pathological complete response and major pathological response.

Among patients receiving preoperative FLOT, 177 (57.6%) completed at least four full-dose cycles. Surgery was performed in 283 cases (92.2%), and 221 patients (72.0%) proceeded to postoperative treatment. Preoperative chemotherapy delays and discontinuations occurred in 90 patients (29.3%) and 15 (4.9%), respectively; postoperative delays occurred in 65 (21.2%) and discontinuations in 25 (8.1%). Gastrointestinal toxicity was the most frequent adverse event, affecting 64.8% of patients before surgery and 65.2% afterward. Grade 3–4 gastrointestinal events occurred in 17 patients (5.5%) preoperatively and 24 (10.9%) postoperatively. R0 resection was reported in 261 of 280 evaluable cases (92.9%).

Pathological complete response was achieved in 8.6% of patients and major pathological response in 26.7%. Patients with either response measure had significantly longer disease-free and overall survival in the survival analyses: the reported hazard ratios were 0.22 and 0.16 for pathological complete response and 0.18 and 0.14 for major pathological response, respectively. The abstract reports p-values of 0.001 and 0.004 for the pathological-complete-response comparisons and p-values below 0.001 for the major-pathological-response comparisons. Overall survival was also significantly longer in patients whose tumours had microsatellite instability, with a reported hazard ratio of 0.00 and p=0.029. These findings are prognostic associations within an observational cohort, not evidence that pathology or biomarker status alone caused the survival differences. The study’s prospective, non-randomised design and the stated 31.2-month median follow-up also constrain comparisons and long-term interpretation, while the supplied abstract does not describe adjustment for potential confounding.

Subject of Research: Long-term observational outcomes of perioperative FLOT in resectable gastric or gastroesophageal junction adenocarcinoma

Article Title: Real world outcomes of perioperative FLOT in an Italian cohort of resectable gastric cancer: long term follow-up of prospective observational Real-FLOT study

Article References: Valle, I., Giommoni, E., Rossini, D., Miceli, C. C., Fornaro, L., Iachetta, F., Pozzo, C., Satolli, M. A., Spallanzani, A., Puzzoni, M., Bergamo, F., Sisani, M., Formica, V., Giovanardi, F., Strippoli, A., Prisciandaro, M., Di Donato, S., Caropreso, G., Salani, F., … Antonuzzo, L. (2026). Real world outcomes of perioperative FLOT in an Italian cohort of resectable gastric cancer: long term follow-up of prospective observational Real-FLOT study. BMC Cancer. https://doi.org/10.1186/s12885-026-16985-1

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16985-1

Keywords: RealFLOT, gastric cancer, gastroesophageal junction cancer, perioperative chemotherapy, FLOT regimen, pathological complete response, major pathological response, overall survival, disease-free survival, microsatellite instability, observational study, Real