Clinical indications and implications of metastasis-directed therapy and primary-site treatment in metastatic urothelial carcinoma.

Abstract

Metastatic urothelial carcinoma (mUC) is traditionally managed with systemic therapy; however, long-term disease control remains uncommon despite advances such as immune checkpoint inhibitors and antibody-drug conjugates. Interest has grown in integrating metastasis-directed therapy (MDT), including metastasectomy and stereotactic body radiotherapy (SBRT), and primary-site treatment (PST) in selected patients, aiming to reduce tumor burden, eliminate resistant clones, and enhance systemic therapy outcomes. Metastasectomy is not standard but may be considered for oligometastatic patients with good performance status and a favorable response to first-line therapy. Retrospective series have shown feasibility and durable control, especially with solitary lung or nodal metastases, although data are limited by selection bias and a lack of randomized trials. SBRT offers high local control and palliation, with a growing role in oligometastatic or oligoprogressive disease to delay progression and complement immunotherapy. PST after a favorable systemic response for metastatic bladder cancer, including conversion or consolidative cystectomy and palliative or ablative radiotherapy, provides additional disease control and symptom relief. In metastatic upper tract urothelial carcinoma, retrospective and SEER-based data studies similarly suggest a survival benefit from nephroureterectomy in selected patients. Circulating tumor DNA is emerging as a complementary biomarker for patient selection and response monitoring in advanced UC cases. Most evidence predates highly effective systemic therapies; thus, the clinical value and optimal integration of MDT and PST remain to be defined, requiring prospective validation and refined patient selection.