The Evolution of Neoadjuvant Treatment for Resectable Esophageal Squamous Cell Carcinoma: Past Achievements, Current Standards, and Future Perspectives
- 1Department of Surgery, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan
Abstract
Neoadjuvant treatment has become an integral component of multidisciplinary management for resectable esophageal squamous cell carcinoma (ESCC). Over recent decades, treatment has evolved from surgery alone to postoperative chemotherapy, neoadjuvant chemotherapy, intensified systemic therapy, neoadjuvant chemoradiotherapy, and, more recently, the incorporation of immune checkpoint inhibitors into curative-intent treatment. This evolution has been driven by persistent challenges including systemic recurrence, locoregional failure, treatment-related toxicity, and heterogeneous treatment response. This review traces the evolution of neoadjuvant treatment for resectable ESCC through landmark clinical trials that have shaped current practice. We discuss the transition from postoperative to neoadjuvant chemotherapy, the development of intensified chemotherapy and neoadjuvant chemoradiotherapy, and the emergence of immunotherapy, distinguishing the established role of adjuvant nivolumab from the emerging role of neoadjuvant immunochemotherapy. We then examine the unresolved relative roles of these strategies and the challenges in treatment selection. Finally, we discuss future directions centered on accurate response assessment, circulating tumor DNA-based molecular residual disease assessment, and response-adapted treatment, with particular emphasis on organ-preserving strategies after a clinical complete response. Although active surveillance has emerged as a potential alternative to immediate surgery in carefully selected patients, accurate identification of residual disease and appropriate surveillance remain essential. Future advances may therefore shift the focus from treatment intensification alone toward response-adapted strategies that can maintain oncological safety while potentially enabling organ preservation.
Related
- Efficacy comparison of neoadjuvant chemotherapy, chemoradiotherapy, and chemoimmunotherapy in resectable esophageal squamous cell carcinoma: short- and long-term outcomes from a propensity score-matched analysis
- Immune checkpoint inhibitors across neoadjuvant, perioperative, and adjuvant settings for resectable non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials
- InDuRanS: neoadjuvant immunochemotherapy followed by surgery or definitive chemoradiotherapy and consolidation durvalumab in resectable and borderline resectable stage IIB-IIIA/B non-small-cell lung cancer.
- Whole-esophageal radiomics and deep learning for predicting the pT and pN categories of resectable esophageal cancer
- Neoadjuvant pepinemab in combination with nivolumab and/or ipilimumab in resectable metastatic melanoma: a pilot biomarker-driven trial
BibTeX
@article{ujiie2026evolution,
title = {{The Evolution of Neoadjuvant Treatment for Resectable Esophageal Squamous Cell Carcinoma: Past Achievements, Current Standards, and Future Perspectives}},
author = {Naoto Ujiie and Yusuke Taniyama and Chiaki Sato and Hiroshi Okamoto and Yohei Ozawa and Hirotaka Ishida and Michiaki Unno and Takashi Kamei},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203350},
url = {https://www.mdpi.com/2072-6694/18/20/3350},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Evolution of Neoadjuvant Treatment for Resectable Esophageal Squamous Cell Carcinoma: Past Achievements, Current Standards, and Future Perspectives
AU - Naoto Ujiie
AU - Yusuke Taniyama
AU - Chiaki Sato
AU - Hiroshi Okamoto
AU - Yohei Ozawa
AU - Hirotaka Ishida
AU - Michiaki Unno
AU - Takashi Kamei
PY - 2026
DA - 2026/10/16
JO - Cancers
DO - 10.3390/cancers18203350
UR - https://www.mdpi.com/2072-6694/18/20/3350
AB - Neoadjuvant treatment has become an integral component of multidisciplinary management for resectable esophageal squamous cell carcinoma (ESCC). Over recent decades, treatment has evolved from surgery alone to postoperative chemotherapy, neoadjuvant chemotherapy, intensified systemic therapy, neoadjuvant chemoradiotherapy, and, more recently, the incorporation of immune checkpoint inhibitors into curative-intent treatment. This evolution has been driven by persistent challenges including systemic recurrence, locoregional failure, treatment-related toxicity, and heterogeneous treatment response. This review traces the evolution of neoadjuvant treatment for resectable ESCC through landmark clinical trials that have shaped current practice. We discuss the transition from postoperative to neoadjuvant chemotherapy, the development of intensified chemotherapy and neoadjuvant chemoradiotherapy, and the emergence of immunotherapy, distinguishing the established role of adjuvant nivolumab from the emerging role of neoadjuvant immunochemotherapy. We then examine the unresolved relative roles of these strategies and the challenges in treatment selection. Finally, we discuss future directions centered on accurate response assessment, circulating tumor DNA-based molecular residual disease assessment, and response-adapted treatment, with particular emphasis on organ-preserving strategies after a clinical complete response. Although active surveillance has emerged as a potential alternative to immediate surgery in carefully selected patients, accurate identification of residual disease and appropriate surveillance remain essential. Future advances may therefore shift the focus from treatment intensification alone toward response-adapted strategies that can maintain oncological safety while potentially enabling organ preservation.
SN - 2072-6694
ER -