Distinct irAEs patterns are further influenced by treatment context (77, 78), as dual checkpoint blockade (PD-1 plus CTLA-4, IO–IO) is frequently used in RCC but not established as standard for other GU cancers such as bladder cancer, where guidelines recommend PD-1/PD-L1 monotherapy (e.g., pembrolizumab, avelumab maintenance) due to excess toxicity without proven survival benefit. The gene discussed is CTLA4; the disease is urinary bladder cancer.