A meta-analysis of cohort studies assessing FLOT regimen in the treatment of esophageal cancer.

Abstract

379 Background: The perioperative FLOT regimen (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) has shown superior outcomes in gastric and gastroesophageal junction adenocarcinomas. However, its effectiveness in esophageal cancer remains uncertain, particularly outside randomized settings. This systematic review and meta-analysis of cohort studies evaluates the comparative efficacy and safety of FLOT versus standard regimens in esophageal cancer. Methods: Following PRISMA guidelines, PubMed, and Cochrane Library were searched from inception till May 5, 2025. Retrospective and prospective cohort studies comparing FLOT with other regimens in esophageal cancer were included. Outcomes assessed included R0 resection rate, postoperative mortality, tumor regression grade (TRG), pathologic complete response (pCR), and completion of neoadjuvant therapy. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The random-effects model was used to calculate the weighted pooled risk ratio (RR) with the corresponding 95% confidence intervals (CI) of our desired outcome. I 2 and χ 2 statistics assessed heterogeneity with a p-value of <0.05, considered statistically significant. Results: Seven cohort studies comprising 4,199 patients (FLOT, n = 2,055; control, n = 2,144) were included. We found that the use of FLOT showed statistically significant results in R0 resection rate (RR, 1.07; 95% CI, 1.01–1.14; P = 0.02), postoperative mortality (RR, 0.35; 95% CI, 0.19–0.64; P = 0.0007) and TRG (RR, 1.45; 95% CI, 1.19–1.77; P = 0.0002). While FLOT demonstrated no statistically significant benefit on pCR (RR, 1.05; 95% CI, 0.68 – 1.63; P = 0.83), or completion of neoadjuvant therapy (RR, 0.98; 95% CI, 0.91–1.07; P = 0.70). All included studies demonstrated low risk of bias (NOS 7–9). Conclusions: Our meta-analysis exhibited that the FLOT regimen was associated with a statistically significant improvement in TRG and R0 resection rate, while also reducing postoperative mortality. This supports the efficacy and safety of FLOT in the management of esophageal cancer. However, FLOT therapy showed no statistically significant benefit on pCR, and completion of neoadjuvant therapy. Therefore, further large-scale studies are needed to better understand the impact of FLOT therapy on esophageal cancer.