Commentary: Balancing Upfront Surgery and Neoadjuvant Therapy in Clinically Node-Negative T2–3 Esophageal Squamous Cell Carcinoma

Abstract

See Article page 117.

Accurate preoperative staging and appropriate treatment selection remain central challenges in the management of locally advanced esophageal squamous cell carcinoma (ESCC). For patients with clinical T2–3N0 disease, the decision between upfront esophagectomy and neoadjuvant chemoradiotherapy (nCRT) followed by surgery requires careful consideration of competing risks. Specifically, clinicians must balance the likelihood of occult nodal metastasis and tumor upstaging against the potential morbidity associated with preoperative therapy.

In the study by Tsai et al. [1], the authors conducted a single-center retrospective analysis of 108 patients with cT2–3N0 ESCC who underwent either upfront esophagectomy or nCRT followed by surgery. Propensity score matching was used to minimize baseline differences between groups. The study reported that, although up to 31.9% of patients in the upfront surgery group experienced T/N upstaging or occult nodal metastasis (22.2%), 5-year overall survival (51.6% vs. 53.8%, p=0.666) and recurrence-free survival (44.8% vs. 48.6%, p=0.864) were comparable between the 2 treatment strategies. Furthermore, recurrence patterns were similar, suggesting that upfront surgery can achieve oncologic outcomes comparable to those of neoadjuvant therapy in carefully selected clinically node-negative patients.

However, these findings should be interpreted in the context of existing evidence supporting neoadjuvant treatment. A multicenter European retrospective study demonstrated that neoadjuvant therapy was associated with a significant survival benefit in patients with clinical T3N0M0 esophageal cancer, underscoring the importance of preoperative treatment in more advanced primary tumors [2]. Similarly, a propensity score–matched analysis reported that nCRT followed by surgery was associated with improved survival compared with surgery alone in clinically node-negative esophageal carcinoma, particularly among patients at higher risk of occult disease [3]. Collectively, these findings support the rationale that neoadjuvant therapy may address subclinical nodal metastasis and improve oncologic control.

Current clinical practice is reflected in the National Comprehensive Cancer Network Guidelines, which recommend a risk-adapted approach. Patients with cT2N0 disease without high-risk features may be considered for upfront esophagectomy, whereas those with cT3N0 disease or unfavorable clinical characteristics are recommended to undergo nCRT followed by surgery [4]. These recommendations are supported by evidence demonstrating improved pathological response rates, higher R0 resection rates, and enhanced locoregional control with nCRT, particularly in ESCC.

Taken together, the findings of Tsai et al. [1] highlight the importance of individualized treatment planning. While upfront esophagectomy may avoid the morbidity associated with chemoradiotherapy in selected low-risk patients, neoadjuvant therapy remains essential for those with a higher tumor burden or an increased likelihood of occult nodal disease. Multidisciplinary evaluation, incorporating advanced imaging modalities such as positron emission tomography/computed tomography and endoscopic ultrasound, is critical for improving staging accuracy and guiding treatment decisions.

Nevertheless, several limitations should be acknowledged. The retrospective design, single-center setting, and relatively small sample size introduce potential selection bias and limit generalizability. In addition, heterogeneity in treatment selection and surgical techniques may further confound interpretation. Future prospective, multicenter studies are needed to refine patient selection criteria and to integrate emerging biomarkers and imaging techniques into clinical decision-making.

In conclusion, both upfront esophagectomy and nCRT followed by surgery represent valid treatment strategies for cT2–3N0M0 ESCC. A personalized, guideline-informed approach that balances tumor stage, biological risk, and patient condition remains essential to optimize oncologic outcomes while minimizing treatment-related morbidity.