Introduction: We present a case of cystitis, which was considered to be an immune‐related adverse event associated with nivolumab administration.Case presentation: A 47‐year‐old man suffered from sudden onset urinary symptoms after 18 cycles of nivolumab treatment for stage IV pulmonary adenocarcinoma. Urine culture and urine cytology were both negative. The symptoms were inferred to be related to nivolumab administration, and a bladder biopsy under spinal anesthesia was performed. The histopathological examination showed the evidence of allergic‐related cystitis. We planned to administer corticosteroids, but the urinary symptoms disappeared after the bladder biopsy. Nivolumab treatment was continued without recurrent bladder symptoms.Conclusion: We reported a case of cystitis after treatment with nivolumab, which served as a reminder to consider the possibility of immune‐related adverse events as a potential cause for any symptoms that develop during treatment with immuno‐oncology drugs.

Importance: Metastatic urothelial carcinoma (mUC) presents a therapeutic challenge with poor outcome. Enfortumab vedotin has emerged as a promising treatment, necessitating a comprehensive evaluation of its effectiveness and safety.Objective: To synthesize the available evidence on enfortumab vedotin, both as monotherapy and in combination with pembrolizumab, as an mUC treatment for the purpose of guiding clinical decision-making and future research.Data Sources: Cochrane Library, MEDLINE (via PubMed), Google Scholar, and Web of Science were searched from database inception to August 31, 2024. Major conference abstracts from 2019 to 2024 were also included. Search strategy used a combination of Medical Subject Heading terms and free-text keywords related to mUC and enfortumab vedotin.Study Selection: Randomized clinical trials and prospective studies investigating enfortumab vedotin in adult patients with mUC were included. Eleven studies met the inclusion criteria.Data Extraction and Synthesis: Two independent reviewers extracted data and assessed study quality using the Cochrane Risk of Bias tool 2 and Risk of Bias in Non-Randomized Studies of Interventions tool. The meta-analysis used a random effects model, while a network meta-analysis was performed using a frequentist approach.Main Outcomes and Measures: Primary outcomes were disease control rate (DCR), objective response rate (ORR), and 1-year survival rate.Results: The 11 included studies (3 randomized clinical trials [27.3%] and 8 nonrandomized prospective studies [72.7%]) involved 2128 patients. Of these patients, 563 (26.5%) received enfortumab vedotin plus pembrolizumab, 814 (38.3%) received enfortumab vedotin without pembrolizumab, and 751 (35.3%) received chemotherapy. Enfortumab vedotin plus pembrolizumab was associated with a pooled DCR of 86% (95% CI, 83%-89%), ORR of 68% (95% CI, 64%-71%), and a 1-year survival rate of 79% (95% CI, 75%-82%). Enfortumab vedotin monotherapy had a pooled DCR of 73% (95% CI, 70%-76%), ORR of 43% (95% CI, 40%-47%), and a 1-year survival rate of 52% (95% CI, 48%-56%). Network meta-analysis revealed that enfortumab vedotin plus pembrolizumab significantly outperformed chemotherapy in ORR (odds ratio [OR], 3.47; 95% CI, 1.49-8.09; P = .004) and 1-year survival (OR, 2.32; 95% CI, 1.75-3.06; P < .001).Conclusions and Relevance: In this systematic review and meta-analysis, enfortumab vedotin plus pembrolizumab showed high response rates in first-line settings, while enfortumab vedotin monotherapy was associated with clinical benefit in later lines of therapy. These findings underscore the importance of personalized treatment approaches, and future research is warranted to refine enfortumab vedotin–based therapies for mUC management.

Background/Objectives: Urothelial carcinoma (UC) treatment has been transformed by immunotherapy and antibody-drug conjugates (ADCs). This review evaluates the current evidence for these approaches and identifies future directions. Methods: We conducted a structured review of clinical trials, meta-analyses, and guidelines published until early 2025. Results: Immune checkpoint inhibitors have established benefits across multiple settings: post-platinum therapy (pembrolizumab, nivolumab), maintenance therapy (avelumab), adjuvant settings for high-risk muscle-invasive disease (nivolumab), and BCG-unresponsive non-muscle-invasive disease (pembrolizumab). Enfortumab vedotin (targeting Nectin-4) has proven effective in post-platinum/post-immunotherapy. Most significantly, enfortumab vedotin plus pembrolizumab has redefined first-line treatment with unprecedented survival benefits (median OS 31.5 months vs. 16.1 months with chemotherapy; HR 0.47), and nivolumab plus gemcitabine-cisplatin improved outcomes in cisplatin-eligible patients. Key challenges include managing unique toxicity profiles, optimizing treatment sequencing, and developing reliable biomarkers. Conclusions: Combination approaches offer the most promising path forward, with future research needed on resistance mechanisms, biomarker development, and expanding these therapies to earlier disease stages.