Metastasis-directed Therapy in the Management of Urothelial Carcinoma: A Systematic Review and Meta-analysis

Background and objective: In this prospectively registered meta-analysis (PROSPERO: CRD42024501283), we pooled data on patients treated with metastasis-directed therapies (MDTs) for metastatic urothelial cancer (mUC). Methods: On January 24, 2024, we searched PubMed (MEDLINE), Scopus, and Google Scholar for studies on consolidative MDT in patients with mUC. The search was updated on August 25, 2024. Reports of MDT for brain metastases were excluded. The survival data were synthesised with a distribution-free approach using individual patient data extracted from Kaplan-Meier plots. The risk of bias was assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Key findings and limitations: We included 19 retrospective and one prospective study, encompassing a total of 616 patients, published between 2003 and 2024. The median age ranged between 56 and 72 yr. Most patients were treated with surgical metastasectomy (73%), and approximately half received MDT as a first line of treatment for metastases. The pooled 2- and 5-yr overall survival (OS) rates were 64% (95% confidence interval [CI] 58–71%) and 38% (95% CI 33–45%). The median OS was 46.2 mo in patients treated for lung metastases (95% CI 28.7–62.6), 31.2 mo in those treated for lymph node metastases (95% CI 16.1–51.8), and 29 mo in those with mixed-location metastases (95% CI 23.8–38.4). The main limitations were heterogeneity, lack of data from comparative studies, and low quality of the evidence. Conclusions and clinical implications: Many patients with mUC selected for MDT achieve long-term survival, particularly those with lung metastases. Although a causal association cannot be established, MDT emerges as a promising research direction, especially in combination with novel systemic therapies capable of eliciting deep, sustained responses.