Neoadjuvant Therapy for Esophageal Cancer

TL;DR

This review explores how pre-surgery treatments for esophageal cancer have evolved, focusing on chemotherapy, radiotherapy, and immunotherapy.

Contribution

The paper provides a comprehensive overview of emerging strategies and challenges in neoadjuvant therapy for esophageal cancer.

Findings

Randomized controlled trials have transformed clinical practice for esophageal cancer treatment.

Neoadjuvant chemoradiation and chemotherapy have established roles based on landmark trials.

Immunotherapy, including checkpoint inhibitors, is an emerging area with ongoing investigations.

Abstract

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.

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.