Beyond the Scalpel: Why FLOT Changed Gastric Cancer—Biological Rationale, Evidence, and Regional Relevance

Abstract

The management of resectable gastric cancer has undergone a fundamental transformation over the past two decades, evolving from a surgery-dominated paradigm to a multimodal approach integrating systemic therapy. The FLOT regimen, combining fluorouracil, leucovorin, oxaliplatin, and docetaxel, has emerged as the current standard of care following demonstration of superior survival outcomes compared with earlier anthracycline-based regimens. However, the benefits of FLOT are not uniform and are strongly influenced by tumor biology, anatomical subsite, surgical quality, host fitness, and regional health care realities. This narrative review examines the evolution of perioperative chemotherapy, the biological rationale underlying FLOT, evidence from landmark trials, and the Indian/low- and middle-income country applicability of modified FLOT. It further discusses toxicity, D2 surgery, chemoimmunotherapy, and circulating tumor deoxyribonucleic acid as a future risk-stratification tool.