The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting featured an oral session on bladder cancer and a presentation by Dr. Jill Hamilton Reeves discussing the primary results of S1600 evaluating the impact of immune-enhancing nutrition on the outcomes of radical cystectomy, which is associated with high complication rates, high infection rates, rapid postoperative muscle wasting, and perioperative malnutrition.
The conceptual model for the high postoperative morbidity is that radical cystectomy induces a proinflammatory cytokine storm, leading to decreased collagen, decreased nitric oxide, impaired T-cell function, and decreased protein translation.1-2
SWOG S1600 was a randomized, double-blind, phase III study comparing the effects of specialized immunonutrition versus oral nutritional supplementation on postoperative complications after radical cystectomy. Specialized immunonutrition is fortified with nutrients such as L-arginine, omega-3 fatty acids, and dietary nucleotides.
Patients scheduled to undergo radical cystectomy for bladder cancer were enrolled and randomized 1:1 to specialized immunonutrition or oral nutritional support based on the following clinical trial design.
The primary outcome was any (grade I or higher) postoperative complications assessed by the Clavien-Dindo scale at 30 days after radical cystectomy. Multivariate logistic regression analysis was used with the following stratification factors:
- Diversion type (neobladder or conduit)
- Preoperative chemotherapy (yes vs. no)
- Nutritional status (well-nourished vs. mildly malnourished)
Additional outcomes included 90-day complications and high-grade (Clavien-Dindo ≥ grade III) complications. Two-year progression-free survival and overall survival were assessed, and differences by arm were reported using the Log-rank test statistic. A protocol-specified intention-to-treat analysis based on all randomized patients and a one-sided alpha = 0.05 test was performed.
The mean age of the 203 patients enrolled (99 taking specialty immunonutritional supplements and 104 taking oral nutritional supplements) was 68.8 years, 20% were female, and 5% were black. Five patients did not meet the eligibility criteria (one patient taking specialty immunonutritional supplements and four patients taking oral nutritional supplements) but were eligible for the intention-to-treat design.
Seventeen patients withdrew consent before the day 30 evaluation, and eight patients were not evaluated. Thus, n = 178 (90 in specialized immunonutrition and 88 in oral nutrition support) were evaluable for the primary outcome at day 30. The proportion of patients who experienced a Clavien-Dindo grade ≥ 1 complication was 62.2% in specialized immunonutrition and 58.0% in oral nutrition support. In multivariate regression, there was no between-group difference in grade ≥ 1 complications (OR 1.18; 95% CI, 0.64-2.18; one-sided p = 0.71). There were no between-group differences in high-grade complications at day 30, all complications or high-grade complications at day 90, or overall.
To date, of all 203 patients, 17 patients receiving specialized immunonutritional agents and 26 patients receiving oral nutritional agents have progressed or died, with 2-year progression-free survival rates estimated to be 77% and 68%, respectively (one-sided p = 0.16). Nine patients receiving specialized immunonutritional agents and 17 patients receiving oral nutritional agents have died, with 2-year overall survival rates estimated to be 87% and 78%, respectively (one-sided p = 0.07).
This study had several limitations: (i) survival outcomes are exploratory and not yet mature and should be interpreted with caution (assessment of 2-year protocol-specified survival outcomes with full follow-up is planned), (ii) the focus on overall complication rates may dilute more specific effects on infection rates and muscle mass and therefore requires further analysis, and (iii) nutritional biomarker data on adherence were collected but have not yet been evaluated.
Dr. Hamilton-Reeves discussed the key findings from S1600, evaluating the impact of immune-enhancing nutrition on radical cystectomy outcomes, and concluded his presentation with the following key message:
- In patients with bladder cancer undergoing radical cystectomy, there was no difference in Clavien-Dindo complication grade by type of dietary supplement.
- Fewer patients in the specialized immunonutrition group experienced disease progression or died, although the difference was not statistically significant.
- Survival follow-up will continue for three years after enrollment.
- Future studies are needed to understand dietary interactions on cancers that are sensitive to immune modulation.
Presenter: Jill Hamilton Reeves, PhD, RD, CSO, Associate Professor, University of Kansas Medical Center, Kansas City, Missouri
Written by: Zachary Klassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, Twitter account @zklaassen_md during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Friday, May 31 – Tuesday, June 4, 2024, in Chicago, Illinois.
References:
- Hamilton-Reeves JM, Bechtel MD, Hand LK, et al. “Effect of immunonutrition on immune responses and infection rates during cystectomy: a pilot randomized controlled clinical trial.” EUR Urol2016 Mar;69(3):389-392.
- Hamilton-Reeves JM, Stanley A, Bechtel MD, et al. “Perioperative immunonutrition modulates the inflammatory response after radical cystectomy: results of a pilot randomized controlled clinical trial.” J Urol2018 Aug;200(2):292-301.
