Gastroesophageal cancers, though relatively uncommon in the U.S., cause significant morbidity and mortality worldwide. For early-stage gastric and gastroesophageal junction (GEJ) adenocarcinoma, the primary goal is cure, achieved through multimodality treatment. Landmark trials demonstrated the benefits of perioperative chemotherapy, such as the MAGIC trial’s pECF regimen, and neoadjuvant chemoradiotherapy, like the CROSS trial’s nCROSS regimen. More recent studies, including FLOT4 and ESOPEC, showed that pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) outperforms these earlier regimens.
A systematic review and network meta-analysis of 15 trials involving 8,072 patients confirmed that pFLOT provides the greatest overall and disease-free survival benefits compared to nCROSS, pECF/ECX, or surgery alone. Adding neoadjuvant chemoradiation to perioperative chemotherapy did not further improve outcomes, highlighting pFLOT’s efficiency as a standalone approach.
While emerging immunotherapy combinations show higher pathologic complete response rates, their effect on long-term survival remains uncertain. Current evidence reinforces pFLOT as the standard of care for resectable gastric and GEJ adenocarcinoma.