Neoadjuvant Chemoradiotherapy Plus Surgery vs. Surgery Plus Adjuvant Therapy for Esophageal Squamous Cell Carcinoma: A Prospective, Randomized Phase III Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Neoadjuvant Chemoradiotherapy
- Conditions
- Not specified
- Sponsor
- Yongtao Han
- Enrollment
- 254
- Locations
- 1
- Primary Endpoint
- OS
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This phase III randomized clinical trial compared the long-term survival and safety of neoadjuvant chemoradiotherapy (NCRT) followed by surgery versus surgery with adjuvant therapy (AT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Conducted at Sichuan Cancer Hospital, patients were randomly assigned to receive either NCRT (chemotherapy and radiotherapy followed by surgery) or AT (surgery followed by adjuvant therapy based on staging).
The primary outcome was overall survival (OS), with secondary outcomes including disease-free survival (DFS), R0 resection rates, and treatment-related toxicity. A total of 245 patients were randomized, and 224 patients were included in the final analysis.
Detailed Description
This study is a prospective, randomized, open-label, phase III clinical trial conducted at Sichuan Cancer Hospital, a high-volume cancer center in China. The primary objective is to compare the long-term survival outcomes of neoadjuvant chemoradiotherapy (NCRT) combined with surgery versus surgery followed by adjuvant therapy (AT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed, resectable, locally advanced thoracic ESCC (staged according to the 8th edition of the AJCC TNM classification) were enrolled and randomized in a 1:1 ratio to the NCRT or AT group. The NCRT group received intensity-modulated radiotherapy (40 Gy in 20 fractions) combined with paclitaxel and carboplatin, followed by surgery. The AT group underwent surgery first, followed by adjuvant therapy (chemotherapy or chemoradiotherapy) determined by postoperative pathological staging based on the 2018 NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers. The study's primary endpoint is overall survival (OS). Secondary endpoints include disease-free survival (DFS), R0 resection rate, pathological complete response (pCR) rate, treatment-related toxicity, and postoperative complications. Safety was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) and the Clavien-Dindo classification for surgical complications. A total of 245 patients were randomized, with 116 patients in the NCRT group and 108 in the AT group achieving R0 resection and included in the final analysis. Kaplan-Meier survival analysis and Cox proportional hazards models were employed to evaluate OS and DFS. This trial seeks to provide high-quality evidence for optimizing treatment strategies in locally advanced ESCC and to highlight the significance of achieving pathological response as a predictor of improved survival. Future studies with larger sample sizes and multi-center participation are needed to validate these findings.
Investigators
Yongtao Han
Chief Investigator, Professor of Thoracic Surgery
Sichuan Cancer Hospital and Research Institute
Eligibility Criteria
Inclusion Criteria
- •Aged 18 to 75 years, both sexes;
- •Histologically confirmed locally advanced (cT1N+M0 or T2-4aNxM0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM stage);
- •Cervical contrast-enhanced CT showed no suspicious metastatic lymph nodes, and imaging studies confirmed no systemic metastasis;
- •Expected to achieve R0 resection;
- •ECOG performance status 0 to 1;
- •No prior antitumor therapy for esophageal cancer, including chemotherapy, radiotherapy (including planned radiotherapy during the study), hormone therapy, or immunotherapy;
- •Measurable lesions according to RECIST v1.1 criteria;
- •No contraindications for surgery based on preoperative evaluation of organ function;
- •Laboratory test results confirm eligibility:
- •Hemoglobin ≥90 g/L;
Exclusion Criteria
- •History of Other Malignancies: 1.
- •Patients who have had malignancies other than esophageal cancer.
- •Bleeding Tendency and Coagulation Disorders: 2.
- •Gastrointestinal bleeding within 6 months prior to randomization. 2.
- •Coagulation disorders at the time of enrollment. 2.
- •Patients receiving thrombolysis or anticoagulant therapy.
- •Cardiovascular and Cerebrovascular Diseases: 3.
- •The following conditions within 12 months prior to randomization:
- •Congestive heart failure classified as NYHA class II or higher.
- •Unstable angina, myocardial infarction, or poorly controlled arrhythmias.
Arms & Interventions
NCRT group
Intervention: Neoadjuvant Chemoradiotherapy
NCRT group
Intervention: Surgery
AT group
Intervention: Adjuvant therapy
AT group
Intervention: Surgery
Outcomes
Primary Outcomes
OS
Time Frame: 5 years
Overall survival
Secondary Outcomes
- R0 resection rate(1 years)
- pathological complete response (pCR) rate(1 years)
- DFS(5 years)
- Adverse Events(1 years)