TOPLINE: 

Neoadjuvant chemoradiotherapy followed by surgery yielded similar 5-year overall survival rates compared to surgery and adjuvant therapy in patients with locally advanced esophageal squamous cell carcinoma, according to findings from a prospective, randomized phase 3 trial.

METHODOLOGY:

• Neoadjuvant chemoradiotherapy followed by surgery and surgery with adjuvant therapy are common strategies for treating locally advanced esophageal squamous cell carcinoma. But with few studies directly comparing the two strategies, it's unclear if one is associated with better outcomes.
• To compare the two approaches, researchers conducted a prospective, open-label phase 3 trial in which patients were randomly assigned 1:1 to either neoadjuvant chemoradiotherapy followed by surgery or surgery followed by adjuvant therapy.
• The study included 254 patients (aged 18-75 years) with histologically confirmed, resectable, locally advanced thoracic esophageal squamous cell carcinoma, staged as cT1N+M0 or cT2-4aNxM0. The trial was conducted at Sichuan Cancer Hospital in China.
• Patients in the neoadjuvant chemoradiotherapy group received intensity-modulated radiotherapy (40 Gy in 20 fractions) with concurrent paclitaxel (135 mg/m²) and carboplatin, followed by surgery. Adjuvant therapy involved chemoradiotherapy; the adjuvant group received the same chemotherapy regimen. Median follow-up was 59.1 months.
• The primary endpoint was overall survival; disease-free survival, pathologic outcomes, and treatment-related toxic effects were secondary endpoints.

TAKEAWAY:

• The 5-year overall survival rate was 59.2% in the neoadjuvant chemoradiotherapy group vs 59.6% in the adjuvant therapy group, indicating no significant difference between the two arms (hazard ratio [HR], 1.01; P = .97).
• Disease-free survival rates were also similar between the two groups at 5 years: 53.1% in the neoadjuvant chemoradiotherapy group vs 56.5% in the adjuvant therapy group (HR, 1.13; 95% CI, 0.77-1.68; P = .53). However, only 28.8% of patients in the neoadjuvant chemoradiotherapy group had positive lymph nodes vs 72.3% in the adjuvant therapy group (P < .001).
• In the neoadjuvant chemoradiotherapy group, patients who achieved a pathologic complete response demonstrated significantly improved overall survival, with 5-year rates of 76.5% vs 52.1% among patients without a pathologic complete response (HR, 0.39; P = .01).
• As for treatment-related adverse events, grade 3 or 4 leukopenia (35.6% vs 26.2%; P = .17) and neutropenia (32.2% vs 23.3%; P = .14) occurred more frequently in the neoadjuvant therapy group, but the differences were not statistically significant. Looking at gastrointestinal toxic effects, the neoadjuvant group had a significantly higher incidence of anorexia (53.4% vs 34.0%, any grade; 3.4% vs 1.0%, grade 3 or 4) and vomiting (22.0% vs 9.7%, any grade) compared with the adjuvant group.

IN PRACTICE:

"The primary finding of this study is that there were no significant differences in long-term survival outcomes" between the two treatment groups, the authors concluded. 

SOURCE:

The study, led by Wenwu He, MD, PhD, Sichuan Cancer Hospital & Institute in Chengdu, China, was published online on January 5, 2026, in JAMA Network Open.

LIMITATIONS:

As a single-center study with a relatively small sample size, the generalizability of findings may be limited, and the statistical power for secondary endpoints could be restricted. 

DISCLOSURES:

The study was supported by grants from the Science and Technology Department of Sichuan Province and the Sichuan Province Clinical Key Specialty Construction Project. The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.