Anti-PD-1 therapy with or without local intervention for oligometastatic esophageal squamous cell carcinoma (ESO- Shanghai20): a prospective, multicenter, randomized controlled, Phase III clinical trial

Abstract Background Anti-PD-1 therapy combined with or without chemotherapy is the standard regimen for metastatic esophageal cancer. Oligometastatic carcinoma is an intermediate state of tumor development between locally advanced and widespread metastasis, with potential long-term survival. The value of the addition of local intervention therapy to standard systemic therapy is still controversial for patients with oligometastasis. The ESO-Shanghai 13 trial demonstrated that systemic therapy combined with local intervention improved progression-free survival and overall survival in patients with oligometastatic esophageal squamous cell carcinoma. However, it is a phase II trial and has two systemic treatment regimens including chemotherapy and chemoimmunotherapy. There were only 43 patients treated with immunotherapy with or without local intervention therapy in ESO-Shanghai 13. To further assess the efficacy of Anti-PD-1 therapy with local intervention therapy in oligometastatic esophageal patients, we initiated a multicenter randomized controlled phase III clinical trial, ESO-Shanghai 20. Methods The ESO-Shanghai20 trial will recruit histology-proven esophageal squamous cell carcinoma patients with genuine oligometastasis (four or fewer metastatic lesions) and the eligible patients will be randomly assigned in a 2:1 ratio to receive either the combined local intervention therapy and systemic therapy (the combined group) or the systemic therapy only (the systemic group). Both groups receive anti-PD-1 with or without chemotherapy for 4 cycles every 21 days, followed by anti-PD-1 maintenance therapy every 21 days for 2 years. The local intervention therapy in this trial includes radiotherapy, surgery, and ablation, and allowed different metastases in the same patient to receive different local intervention treatment modes according to the characteristics of the metastatic site. The expected enrollment time is 36 months, and the follow-up time is 24 months. The combined treatment group and the systemic treatment group required 236 and 118 samples, respectively, and a total of 354 cases needed to be enrolled. The primary endpoint is progression free survival, and the second endpoint is overall survival and the toxicity and safety of the treatment. Discussion If the result of ESO-Shanghai20 shows that the combination of local intervention therapy with anti-PD-1 therapy is safe and promising for patients with oligometastatic esophageal squamous cell carcinoma, this study will provide a basis for the precise stratified treatment of patients with advanced esophageal squamous cell carcinoma. Trial registration NCT06190782.