Immune-Enhancing Nutrition and Outcomes After Radical Cystectomy: A Randomized Clinical Trial.

Abstract

Radical cystectomy for bladder cancer is associated with high complication rates. Evidence supporting perioperative specialized immunonutrition for reducing complications is limited. To determine whether perioperative specialized immunonutrition reduces 30-day complications compared with standard oral nutrition support among adults undergoing radical cystectomy. This multicenter, randomized, double-blind, phase 3 clinical trial (SWOG S1600) conducted at 13 US academic and community sites within the National Cancer Institute National Clinical Trials Network and National Community Oncology Research Program enrolled patients from March 5, 2019, through October 19, 2023, with 30-day complications assessed through day 90 and survival outcomes through 2 years. Participants included adults with bladder cancer scheduled for radical cystectomy who could swallow oral liquids and did not have severe malnutrition. Statistical analysis was performed from January 2024 to December 2026. Participants consumed drinks 3 times daily for 5 days before and after surgery. Both drinks used the same base formula. The immunonutrition product contained added l-arginine, ω-3 fatty acids, and dietary nucleotides. Adherence was 94.5% (52 of 55), measured using the plasma arachidonic acid to eicosapentaenoic acid biomarker. Analysis was performed on a modified intent-to-treat basis. The primary outcome was any 30-day complication (Clavien-Dindo grade ≥1). A 65% complication rate and a 35% relative reduction were prespecified. Secondary outcomes included high-grade complications at 30 and 90 days, adverse events, and 2-year disease-free and overall survival. Of the 203 participants enrolled, the median age was 68.8 years (range 32.0-95.2 years) and 162 (79.8%) were male. Of 203 randomized (99 immunonutrition, 104 standard), 17 withdrew, and 8 lacked 30-day data, yielding 178 evaluable participants (90 immunonutrition, 88 standard). Any 30-day complication occurred in 62.2% of patients (56 of 90) receiving immunonutrition and 58.0% of patients (51 of 88) receiving standard nutrition (odds ratio [OR], 1.18; 95% CI, 0.64-2.18). High-grade 30-day complications occurred in 11.1% of patients (10 of 90) receiving immunonutrition vs 12.5% of patients (11 of 88) receiving standard nutrition (OR, 0.86; 95% CI, 0.34-2.17). Two-year overall survival was 87.4% among patients receiving immunonutrition vs 78.2% among patients receiving standard nutrition, and disease-free survival was 77.0% among patients receiving immunonutrition vs 67.5% among patients receiving standard nutrition. Adverse events occurred for 34.1% of patients (31 of 91) receiving immunonutrition and 20.5% of patients (18 of 88) receiving standard nutrition, with nausea most common. In this randomized clinical trial of adults undergoing radical cystectomy, perioperative specialized immunonutrition did not reduce 30-day complications compared with standard oral nutrition. Differences in 2-year survival favored immunonutrition but were not statistically significant. Further mechanistic evaluation and subgroup analyses are warranted. ClinicalTrials.gov Identifier: NCT03757949.