Narrative review on immune-related adverse events (irAEs) of immune checkpoint inhibitors in the adjuvant therapy of urological cancers.

Abstract

Background and objective: Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC). Their expanding use in the adjuvant setting, aimed at eliminating micrometastatic disease post-surgery, holds significant promise. However, balancing potential survival benefits with the risk of immune-related adverse events (irAEs) in patients who are otherwise disease-free requires careful consideration. This review evaluates current evidence on adjuvant ICIs in UC and RCC, with emphasis on clinical efficacy, irAE profiles, and strategies for mitigating toxicity.

Methods: A targeted literature search was performed across PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, supplemented by manual review of American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference abstracts, to identify relevant studies on adjuvant ICI therapy in urological malignancies between 24 September 2024 and 25 January 2025. Relevant data on efficacy, safety, and irAE management were synthesized to highlight critical findings and research gaps.

Key content and findings: Adjuvant ICIs have shown meaningful improvements in disease-free survival for patients with high-risk UC and RCC. Grade ≥3 irAEs, particularly endocrine toxicities such as hypothyroidism, adrenal insufficiency, and hypophysitis, are relatively frequent and often irreversible, necessitating lifelong hormone replacement and long-term follow-up. Although some trials have not demonstrated overall survival advantages, emerging evidence suggests biomarkers such as circulating tumour DNA (ctDNA) could guide more precise patient selection. Optimising irAE management is pivotal, as these events can significantly affect quality of life in a population that may remain disease-free.

Conclusions: Adjuvant immunotherapy represents a potentially significant advance in UC and RCC, offering improved outcomes for select patients. Yet, the persistent nature of irAEs calls for vigilant surveillance, robust biomarker development, and integration of patient-reported outcomes to ensure informed clinical decision-making. The next frontier will rely on better risk stratification and toxicity mitigation to translate disease-free gains into durable, life-extending benefits. Future research that refines patient selection criteria and irAE management will be crucial for translating these survival gains into long-term benefits and shaping evidence-based guidelines in urological oncology.