Oncological Outcomes and Safety Profiles of Adjuvant Nivolumab in Muscle-Invasive Urothelial Carcinoma.

OBJECTIVES: Perioperative immunotherapy has become the standard of care in patients with high-risk muscle-invasive urothelial carcinoma (MIUC). This study aimed to clarify oncological outcomes and safety profiles of adjuvant nivolumab therapy in MIUC, focusing on upper tract urothelial carcinoma (UTUC).

METHODS: This multicenter study comprised 97 patients undergoing removal of primary tumors, followed by adjuvant nivolumab therapy with a potential follow-up period ≥ 12 months. Patients were divided according to the primary tumor location: bladder cancer (BC), n = 66 (68%); UTUC, n = 31 (32%). Multivariable Cox regression analyses were applied to identify prognostic factors for disease-free survival (DFS).

RESULTS: Before surgery, 38% of patients had an estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2, but this proportion increased to 57% at nivolumab initiation with 19% of UTUC having eGFR < 30. The overall DFS at 6 months was 61.5%. DFS did not differ significantly between BC and UTUC (p = 0.83). On multivariable analyses, a higher absolute eosinophil count was significantly associated with worse DFS (HR 2.24; 95% CI, 1.24-4.03, p = 0.007), while primary tumor location was not. Immune-related adverse events (irAEs) of adrenal insufficiency and hypophysitis occurred in 8% and 4% of patients, respectively, with grade ≥ 3 occurring at 3.3-18.3 months.

CONCLUSIONS: Adjuvant nivolumab therapy may provide comparable oncological outcomes between BC and UTUC. Baseline eosinophil count was an independent prognosticator for DFS. The incidences of adrenal insufficiency and hypophysitis appeared higher in our real-world data. Clinicians should recognize these irAEs due to nonspecific symptoms and considerable variability in time of onset.