ESORES-Trial: Surgery as needed versus surgery on principle in patients with postneoadjuvant clinical complete tumor response of esophageal cancer.

TPS4185 Background: A substantial fraction of patients with esophageal cancer (EC) shows post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients. Active surveillance (AS) and surgery as needed may be a treatment alternative for patients with clinical complete response (cCR). Methods: ESORES is a multicenter randomized controlled parallel-group non-inferiority trial. Patients are randomized either to surgery on principle and subsequent follow-up (Arm B) or clinical response evaluation (CRE) and surgery as needed (Arm A). CRE consists of esophagogastroscopy with deep biopsies (EGD), endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) of suspicious lymph nodes, and F18-FDG-PET CT. In case of residual tumor (non-CR) after CRE, treatment is surgery. Patients with cCR will proceed with AS and surgery only if local regrowth occurs. AS comprises EGD, EUS-FNA and CT-Thorax/Abdomen at 3/6/9/12/18/24 months and yearly thereafter. A sample size of 670 patients is needed to demonstrate non-inferiority of Arm A vs. Arm B with regard to overall survival (OS) at a one-sided significance level of 5%, choosing a hazard ratio of 1.325 as non-inferiority margin which corresponds to a difference in 3-year OS rates of 8%. Superiority with regard to quality of life will be evaluated hierarchically only after non-inferiority with respect to OS has been shown. Key inclusion criteria: histologically verified EC, TNM stage ycT0-3 ycN0 ycM0, completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT) (irrespective of specific protocol), no visible lymphatic or distant metastasis in routine postneoadjuvant CT. Key exclusion criteria: postneoadjuvant dysphagia and/or esophageal obstruction, tumors of the cervical esophagus, tumors with direct proximity to the membranous part of the central airways (if regrowth is suspected to evoke locally irresectable ryT4b-stage), TNM stage cT4/ycT4 and/or cM1/ycM1, tumor progression during/after nCT/nCRT, and nCRT with >50 Gy radiation dose. Primary endpoints (hierarchically tested): 1) OS, 2) EORTC QLQ C30 global quality of life subscale. Secondary endpoints: Efficacy: long term tumor control, disease free survival, distant metastasis/local recurrence/regional recurrence; quality of life: EORTC QLQ C30, QLQ OES18, fear of progression: FoP-Q-12, surgery-free survival time in Arm A, patients’ satisfaction: EORTC OUT-PATSAT7; economic impact: days and costs of hospitalization; Safety: Interventional Safety: 3-Year-Comprehensive Complication Index, Oncological Safety (diagnostic accuracy of CRE, resection status (R0/R1/R2), irresectable regrowth during AS). Enrollment of patients started on January 30 th , 2024. Clinical trial information: DRKS00032613 .