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Esophageal Cancer Research and Treatment / Colorectal Cancer Surgical Treatments / Gastric Cancer Management and Outcomes · Review
Clinical and Preventive Medicine · August 13, 2026
A consensus or society position rather than new primary data.
This narrative review demonstrates that the FLOT regimen improves survival and pathological complete response rates compared to older regimens (ECF) and surgery alone, with FLOT4 showing a threefold increase in pCR. Total neoadjuvant FLOT achieves high R0 resection (86%) and pCR (20%) rates without increasing postoperative complications, but the authors acknowledge no definitive evidence yet that TNT improves long-term survival over standard perioperative FLOT, and perioperative chemotherapy remains the current standard of care.
Narrative literature review. Studies of patients with locally advanced gastric adenocarcinoma and gastroesophageal junction adenocarcinoma treated with perioperative or neoadjuvant chemotherapy (primarily FLOT-based regimens). Intervention: FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) administered as total neoadjuvant therapy or perioperative chemotherapy. Compared with: Surgery alone, ECF regimen, standard neoadjuvant chemoradiotherapy (CROSS), and standard perioperative chemotherapy.
FLOT4 trial demonstrated FLOT provides superior outcomes compared with ECF, including a threefold increase in pathological complete response rate NeoFLOT phase II trial achieved R0 resection rate of 86% and pCR rate of 20% MSKCC analysis (2023) showed most patients completed all preoperative FLOT cycles without an increase in postoperative complications
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Clinicians should recognize FLOT as the current standard regimen for perioperative chemotherapy in locally advanced gastric and GEJ adenocarcinoma. Total neoadjuvant FLOT is a promising strategy to ensure completion of systemic therapy and increase pathological response rates, but should not yet replace standard perioperative chemotherapy pending long-term survival data from prospective studies.
A narrative review synthesizing evidence from key trials (MAGIC, FLOT4, NeoFLOT, ESOPEC) to evaluate FLOT regimen efficacy in locally advanced gastric and GEJ adenocarcinoma, concluding perioperative chemotherapy remains standard of care but TNT is promising pending long-term survival data.
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Clinicians should recognize FLOT as the current standard regimen for perioperative chemotherapy in locally advanced gastric and GEJ adenocarcinoma. Total neoadjuvant FLOT is a promising strategy to ensure completion of systemic therapy and increase pathological response rates, but should not yet replace standard perioperative chemotherapy pending long-term survival data from prospective studies.
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Introduction. Gastric cancer is a leading cause of cancer mortality worldwide, and outcomes for patients with locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma remain poor. Perioperative chemotherapy became the standard of care after the MAGIC and FNCLCC/FFCD trials demonstrated improved survival compared with surgery alone. The FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) subsequently demonstrated superior efficacy and has become the current standard of care. However, many patients do not complete the planned adjuvant chemotherapy because of postoperative complications or disease progression, prompting interest in delivering the entire chemotherapy course preoperatively as total neoadjuvant therapy (TNT) using the FLOT regimen.Aim. To evaluate the efficacy and safety of total neoadjuvant chemotherapy using the FLOT regimen in patients with locally advanced gastric adenocarcinoma and gastroesophageal junction adenocarcinoma.Materials and methods. A narrative literature review was performed. Relevant studies were identified through searches of Scopus, Web of Science, MEDLINE, Cochrane Library, EMBASE, and Global Health. Key clinical trials (MAGIC, FNCLCC/FFCD, FLOT4, NeoFLOT, ESOPEC, etc.) and retrospective analyses of perioperative and neoadjuvant therapy were analyzed.Results. The MAGIC (UK) and FNCLCC/FFCD (France) trials confirmed that adding chemotherapy to surgery improves patient survival. The FLOT4 trial demonstrated that the FLOT regimen provides superior outcomes compared with ECF, including improved survival and a threefold increase in the pathological complete response (pCR) rate. Moreover, the phase II NeoFLOT trial and an analysis from Memorial Sloan Kettering Cancer Center (MSKCC, 2023) demonstrated the feasibility of total neoadjuvant chemotherapy: NeoFLOT achieved an R0 resection rate of 86% and a pCR rate of 20%, while the MSKCC experience showed that most patients completed all preoperative FLOT cycles without an increase in postoperative complications. In addition, the ESOPEC trial (2024) demonstrated that perioperative FLOT chemotherapy resulted in superior survival outcomes compared with standard neoadjuvant chemoradiotherapy (CROSS) in patients with esophageal and GEJ adenocarcinoma.Conclusions. The introduction of the FLOT regimen has significantly improved the treatment outcomes of locally advanced gastric and GEJ adenocarcinoma by increasing R0 resection rates as well as overall and disease-free survival. Delivering the entire FLOT regimen preoperatively is a promising strategy to ensure completion of systemic therapy and increase pCR rates without compromising surgical outcomes. However, there is currently no definitive evidence that total neoadjuvant FLOT improves long-term survival compared with standard perioperative chemotherapy. Further prospective studies are required, while perioperative chemotherapy remains the current standard of care.
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