A multicenter randomized controlled trial of esophagectomy with or without prophylactic supraclavicular node dissection: A phase III trial (JCOG2013, MODERN3)

TPS474 Background: Supraclavicular lymph nodes (SCLN) have been regarded as regional nodes of thoracic esophageal cancer in Japan and resected along with cervical paraesophageal lymph nodes as a cervical part of the standard three-field dissection, while the involvement of SCLN is regarded as distant metastasis in Western countries. However, there is no clear evidence that supports or rejects prophylactic SCLN dissection. As postoperative SCLN metastasis can often be managed by either surgery or chemoradiotherapy at the time of relapse, routine prophylactic SCLN dissection may not be essential. Here we conduct the clinical trial to confirm the non-inferiority of esophagectomy with D2 lymphadenectomy except for SCLN to standard D2 lymphadenectomy in terms of overall survival (OS) for patients with resectable upper or middle thoracic esophageal cancer. Methods: Eligibility criteria include the followings; upper or middle thoracic esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid cell carcinoma with clinical stage I, II, III, or IVA (except for T4) based on the 8th UICC-TNM, age 18 to 80, ECOG performance status 0 or 1, and adequate organ function. Neoadjuvant chemotherapy (cisplatin plus 5- fluorouracil or docetaxel plus cisplatin plus 5-fluorouracil) is allowed, but preoperative chemoradiotherapy is not allowed. Patients are randomly assigned to the following two arms using the minimization method with a random component to balance institution, clinical stage (Stage I (T1N0M0) versus Stage I (T1N1M0)/II/III/IVA), age (76 or older versus 75 or younger), and tumor location (upper thoracic versus middle thoracic). Patients undergo either esophagectomy with standard D2 dissection (Arm A) or esophagectomy with D2 lymphadenectomy except for SCLN (Arm B). The primary endpoint is OS in all randomized patients. The secondary endpoints are relapse-free survival, the incidence of perioperative and delayed complications, the incidence of SCLN recurrence, the incidence of salvage cervical treatment, the proportion of synchronous cervical and abdominal procedure, and operation time and the number of operating surgeons. A sample size of 456 patients would be required to observe 147 events to demonstrate the non-inferiority of Arm B in terms of OS, with a one-sided alpha of 5%, power of 70%, an accrual period of 5 years, a follow-up period of 3 years, and a non-inferiority margin of 6% at 3-year OS, assuming the expected 3-year OS of Arm A and Arm B are 80% and 81%, respectively. The planned sample size was set at 480 patients (240 patients per arm). This trial was registered at the Japan Registry of Clinical Trials (jRCT) as study number jRCT1030220248 and started in August 2022. Clinical trial information: jRCT1030220248 .