# Clinical Trials Update in Resectable Esophageal Cancer

## TL;DR

This paper reviews recent advances in treating resectable esophageal cancer, including immunotherapy and minimally invasive surgery, and highlights new clinical trial results.

## Contribution

The paper provides an updated overview of clinical trials and treatment strategies for resectable esophageal cancer, emphasizing the role of immunotherapy and minimally invasive surgery.

## Key findings

- Perioperative chemotherapy with FLOT regimen improves survival in esophageal adenocarcinoma compared to chemoradiotherapy.
- Adding durvalumab to FLOT chemotherapy improves event-free survival in resectable esophageal cancer.
- Minimally invasive and robotic-assisted esophagectomy reduces perioperative morbidity without compromising oncologic outcomes.

## Abstract

The treatment of resectable esophageal cancer has undergone substantial transformation over the past decade, driven by advances in systemic therapy, immunotherapy, and surgical technique. Multimodal treatment remains the cornerstone of care for locally advanced disease, traditionally combining induction chemotherapy or chemoradiotherapy followed by esophagectomy. More recently, immune checkpoint inhibitors have emerged as a major therapeutic advance, being incorporated into both induction and adjuvant treatment strategies. These agents have demonstrated meaningful improvements in pathologic response rates, disease-free survival, and event-free survival in selected patient populations. At the same time, surgical management has evolved with the widespread adoption of minimally invasive and robotic-assisted esophagectomy, offering equivalent oncologic outcomes with improved perioperative recovery and reduced morbidity. This review summarizes the current evidence supporting modern multimodality treatment approaches for resectable esophageal cancer, highlights key completed and ongoing clinical trials, and explores emerging strategies such as adoptive cell transfer therapy that may further refine personalized treatment in the future.

Management of resectable esophageal cancer has evolved into a multidisciplinary paradigm centered on multimodality therapy. Historically, induction chemoradiotherapy followed by surgery, as established by the CROSS trial, became the standard of care for locally advanced disease due to improvements in R0 resection rates and overall survival. More recently, the ESOPEC trial reexamined this paradigm in esophageal adenocarcinoma, demonstrating superior survival and improved systemic disease control with perioperative chemotherapy using the FLOT regimen compared with chemoradiotherapy. In parallel, the MATTERHORN trial further advanced perioperative treatment by showing improved event-free survival with the addition of the immune checkpoint inhibitor durvalumab to FLOT chemotherapy. Alongside these systemic therapy advances, surgical management has transitioned toward minimally invasive and robotic-assisted esophagectomy, offering equivalent oncologic outcomes with reduced perioperative morbidity. This review summarizes the evolving evidence from pivotal clinical trials, highlights ongoing studies integrating immunotherapy, and discusses emerging strategies such as adoptive cell transfer which currently is under investigation for metastatic recurrence, but in the future may provide additional treatment options for resectable esophageal cancer.