Spleen Preservation Versus Splenectomy in Left Pancreatectomy for Pancreatic Ductal Adenocarcinoma (SPLENDID)

Overview

Rationale: During left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), routine en-bloc splenectomy is performed to achieve complete nodal clearance of the splenic hilum. However, evidence that splenectomy improves survival is lacking, while splenectomy may increase postoperative morbidity and has lifelong consequences related to loss of splenic function. Spleen-preserving left pancreatectomy (SPLP) may be a safe alternative, but high-quality evidence is lacking. Objective: To compare SPLP with left pancreatectomy with splenectomy (LPS) regarding overall survival and major postoperative morbidity in patients with resectable or borderline resectable PDAC. Study design: An international, randomized, controlled, multicenter, non-inferiority trial. Study population: Two groups of 180 patients (360 in total) with proven or suspected resectable or borderline resectable PDAC requiring left pancreatectomy. Intervention: Spleen-preserving left pancreatectomy (SPLP) Control: Left pancreatectomy with splenectomy (LPS)

Rationale: During left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), routine en-bloc splenectomy is performed to achieve complete nodal clearance of the splenic hilum. However, there is no evidence that routine splenectomy improves survival. Splenectomy has been associated with increased postoperative morbidity, lifelong vaccination requirements, and risk of overwhelming post-splenectomy infection. In addition, lymph node metastases in the splenic hilum are uncommon (\~4%), and preservation of splenic immune function is becoming increasingly important with the emergence of novel immunotherapies. Spleen-preserving left pancreatectomy (SPLP) may therefore be a safe alternative to routine splenectomy, but no randomized trials have evaluated this approach. Objective: To compare SPLP with left pancreatectomy with splenectomy (LPS) regarding (1) overall survival over a 3-year period, assessed using restricted mean survival time (RMST), and (2) major postoperative complications within 90 days (Clavien-Dindo grade III or higher) in patients with resectable or borderline resectable PDAC. Study design: An international randomized multicenter non-inferiority trial performed in high-volume pancreatic centers. Participating centers perform at least 15 left pancreatectomies annually, and participating surgeons have completed at least 30 SPLPs (for any indication) and 15 left pancreatectomies for PDAC. Randomization will be performed in a 1:1 ratio using a secure web-based system, stratified for receipt of neoadjuvant therapy (yes/no) and tumor location (body/neck versus tail). Study population: Two groups of 180 patients (360 in total) with proven or suspected resectable or borderline resectable PDAC requiring left pancreatectomy. Intervention: Spleen-preserving left pancreatectomy. Control: Left pancreatectomy with splenectomy. Main study parameters/endpoints: The primary endpoint is overall survival over a 3-year period, assessed using RMST. The main secondary endpoint is major postoperative morbidity within 90 days (Clavien-Dindo grade III or higher). Other secondary outcomes include quality of life, R0 resection rate, disease-free survival, time to and site of recurrence, receipt, timing and completion of adjuvant therapy, pancreas-specific and general postoperative complications, unplanned splenectomy in the SPLP group, secondary splenectomy, spleen- and asplenia-related complications, time to functional recovery, length of hospital stay, health-care resource utilization, and cost-effectiveness.