Immune-Enhancing Nutrition and Outcomes After Radical Cystectomy: A Randomized Clinical Trial
In brief
Immunonutrition does not cut 30-day complications after radical cystectomy (62% vs 58%)
In a double-blind trial of 178 patients, peri-operative immunonutrition yielded a 62% complication rate versus 58% with standard oral nutrition, showing no meaningful reduction. Two-year survival appeared higher with immunonutrition (87% vs 78%), but differences were not statistically significant and nausea was more common. Further analysis is needed to clarify any long-term benefit.
- Journal
- JAMA network open (Q1)
- Published
- 1 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jill M Hamilton-Reeves, Joseph M Unger, Jeffrey M Holzbeierlein, Danika L Lew, J Ryan Mark, Siamak Daneshmand, et al.
- PMID
- 42475098
- DOI
- 10.1001/jamanetworkopen.2026.23622
Why clinicians should know about it
Abstract
IMPORTANCE: Radical cystectomy for bladder cancer is associated with high complication rates. Evidence supporting perioperative specialized immunonutrition for reducing complications is limited. OBJECTIVE: To determine whether perioperative specialized immunonutrition reduces 30-day complications compared with standard oral nutrition support among adults undergoing radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03757949.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.