Neoadjuvant Therapy for Esophageal Cancer
1
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44106, USA
2
Department of Cardiothoracic Surgery, Albany Medical Center, Albany, NY 12208, USA
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(5), 750; https://doi.org/10.3390/cancers18050750
Submission received: 9 December 2025
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Revised: 16 February 2026
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Accepted: 21 February 2026
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Published: 26 February 2026
(This article belongs to the Special Issue Current Issues, Innovations, and Emerging Therapies in Thoracic Surgical Oncology)
Simple Summary
This review focuses on the evolving landscape of neoadjuvant therapy for esophageal cancer, highlighting current evidence, rationale, and emerging strategies. We will first examine the historical context and limitations of surgery alone, emphasizing the need for preoperative interventions. The review will discuss the role of neoadjuvant chemotherapy, chemoradiation, and immunotherapy, summarizing landmark trials as they relate to clinical practice and contemporary guidelines.
Abstract
Background: Esophageal cancer remains one of the most aggressive and fatal malignancies worldwide. Historically, therapeutic strategies relied primarily on neoadjuvant chemotherapy or radiotherapy and surgery, but over the past two decades, randomized controlled trials have driven a major transformation in clinical practice. Methods: This narrative review synthesizes the evolution of evidence-based management from early cytotoxic regimens to modern, histology-specific treatment pathways. We examine landmark trials establishing the roles of neoadjuvant chemoradiation and chemotherapy, along with emerging data on immunotherapy—including checkpoint inhibitors. Persistent challenges include optimizing treatment selection based on molecular profiling, improving response prediction, and managing toxicity in an aging population. Conclusions: We conclude by highlighting key gaps in current evidence and outlining future directions and ongoing clinical investigations.
