Background: Disitamab vedotin (DV, RC48-ADC) has shown promising efficacy and manageable safety as monotherapy or combined with immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) patients progressing after systemic chemotherapy. This study evaluates the efficacy and safety of RC48-ADC plus ICIs in metastatic upper tract urothelial carcinoma (mUTUC) in a real-world setting. Methods: This retrospective, multicenter study included 198 mUTUC patients treated with RC48-ADC plus ICI at 23 clinical centers between June 2021 and December 2023. Data were analyzed from July to September 2024. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to objective response, and treatment-related adverse events (TRAEs). Result: Among the patients, 122 (61.6%) received combination therapy as first-line treatment, while 76 (38.4%) as second-line or beyond. ORR was 58.6% (95% CI: 51.4–65.5), with a median PFS of 13.0 months; median OS was not reached. Subgroup analyses showed consistent ORR across all subgroups. Adverse events (AEs) occurred in 79.8% of patients, with grade 3–4 AEs in 19.7%. Common AEs included neuropathy (40.4%), fatigue (26.8%), alopecia (25.3%), and rash (21.7%). The main limitations of this study include its retrospective design and the population of the study only include patients from China, leading to potential selection bias. Conclusions: RC48-ADC combined with ICIs demonstrated robust antitumor activity and a favorable safety profile in real-world mUTUC, particularly in selected patient groups. Further studies are needed to explore its potential in this high-risk population.

Objective: The DNA methylation urine test, a noninvasive early detection method for upper tract urothelial carcinoma (UTUC), is currently in full swing. This study aimed to systematically assess its diagnostic performance on UTUC. Materials and methods: PubMed, Scopus, Embase, and Cochrane were our main databases when searching articles published from January 2000 to December 2023. Sensitivity and specificity were study primary endpoints. I ² was used to evaluated heterogeneity, meanwhile subgroup and meta-regression analyses were adopted to investigated the source of heterogeneity. Sensitivity analysis was performed to evaluate the result robustness, while Deeks’ funnel plot asymmetry test was for the publication bias. Results: Nine studies with 1326 patients were included. The pooled sensitivity was 0.89 (95% CI: 0.83–0.93) and specificity were 0.91 (95% CI: 0.83–0.96). The area under the receiver operating characteristic curve was 0.96 (95% CI: 0.93–0.97). Substantial heterogeneity was found during the data synthesis, whereas the pooled results remained robust in the sensitivity analysis. None of the potential covariates—urine sample collection method, population, country, methylation test method, or tumor grade—could account for the heterogeneity. Conclusion: DNA methylation urine test is a promising method with high efficiency for UTUC early detection. Nevertheless, owing to the significant heterogeneity, more well-organized studies are warranted to further explore its diagnostic efficiency and application context.