# Prognostic Impact of Adjuvant Immunotherapy in Patients with High-Risk Upper Tract Urothelial Cancer: Results from the ROBUUST 2.0 Collaborative Group

## TL;DR

This study found that immunotherapy after surgery does not improve survival for high-risk upper tract urothelial cancer patients.

## Contribution

The study provides real-world evidence that adjuvant immunotherapy may not benefit high-risk UTUC patients.

## Key findings

- Adjuvant immunotherapy was not associated with improved recurrence-free or overall survival.
- Lymph node involvement remained a strong predictor of poor survival outcomes.
- No significant benefit was observed from adjuvant immunotherapy in this patient group.

## Abstract

This study investigated the effect of immunotherapy on outcomes in patients with high-risk upper tract urothelial carcinoma (UTUC) following surgery. Using a large multi-institutional database, outcomes were compared between patients treated with immunotherapy and a matched group who received no additional therapy. Matching was based on tumor category, lymph node involvement, and prior chemotherapy. Results showed no significant improvement in recurrence-free or overall survival with immunotherapy. However, the presence of cancer in lymph nodes remained a strong predictor of poor survival. These findings suggest that immunotherapy may not provide added benefit in the current setting and highlight the need for better risk-based treatment strategies in high-risk UTUC.

Background/Objective: The impact of adjuvant immunotherapy (IO) on the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. This study examines the association of adjuvant IO with oncologic outcomes in patients with high-risk UTUC. Methods: This retrospective study reviewed patients with high-risk UTUC treated with adjuvant IO using the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST) database. Propensity-score-matched analysis (nearest-neighbor algorithm, caliper 0.1) was conducted to compare patients receiving adjuvant IO versus those who did not, with matching based on pathologic T and N category and receipt of neoadjuvant chemotherapy. Associations between adjuvant IO and urothelial recurrence-free survival (URFS), non-urothelial recurrence-free survival (NRFS), and overall survival (OS) were estimated using a Cox proportional hazards model. Results: Seventy-five patients received adjuvant IO following nephroureterectomy (median four cycles, including eleven (14.7%) nivolumab, thirty-one (41.3%) pembrolizumab, four (5.3%) atezolizumab, and twenty-nine (38.6%) other agents. These patients were matched to 68 patients without adjuvant therapy. Median follow-up times were 17 (IQR, 10–29) months and 20 (9–44) months for IO and no adjuvant therapy, respectively. Multivariable analysis revealed that adjuvant IO was not associated with URFS, NRFS, or OS. Pathologic nodal involvement (HR 7.52, p < 0.001) was the only independent predictor of worse OS. Conclusions: In this real-world retrospective data set, adjuvant IO does not have an impact on oncologic outcomes of UTUC patients following extirpative surgery.