ESOPEC trial: enhancing treatment approaches for esophageal adenocarcinoma

Abstract

Esophageal cancer is a highly lethal cancer with notable global variations in incidence and risk factors. In the U.S., it ranks as the fifth most common gastrointestinal cancer, with around 16,940 new cases annually, while globally, it is the sixth most common cancer. Significant regional disparities are highlighted by the "esophageal cancer belt" across northern Iran, southern Russia, central Asia, and northern China, where squamous cell carcinoma (SCC) dominates, comprising 90% of cases. In contrast, the U.S. has seen a rise in esophageal adenocarcinoma, primarily due to obesity and gastroesophageal reflux disease, with SCC rates declining as tobacco and alcohol use decrease. Key trials have shaped current treatment approaches. The CROSS trial (2012) showed a survival advantage with neoadjuvant chemoradiotherapy (carboplatin/paclitaxel with radiotherapy) plus surgery over surgery alone, extending median overall survival (OS) from 24 to 49.4 months. The FLOT4 trial (2017) established perioperative FLOT chemotherapy as superior to ECF/ECX, with median OS increasing from 35 to 50 months. The Neo-AEGIS trial (2020) found comparable OS between the CROSS and perioperative chemotherapy regimens, supporting treatment flexibility. Recently, the ESOPEC trial (ASCO 2024) demonstrated a median OS benefit with perioperative FLOT (66 months) over CROSS (37 months) in resectable esophageal adenocarcinoma, positioning FLOT as the preferred strategy. These findings highlight the value of tailored, multimodal therapies in enhancing survival and quality of life for esophageal adenocarcinoma patients. Future research will explore immunotherapy's role and the potential to omit surgery in patients achieving a complete pathological response.

Keywords

Esophageal cancer / esophageal adenocarcinoma / neoadjuvant chemoradiation / perioperative chemotherapy / FLOT regimen / CROSS protocol / survival benefit

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