Site-specific heterogeneity in treatment response among patients with metastatic bladder cancer: implications for oligometastatic disease-a retrospective cohort study

Oligometastatic bladder cancer (OMBC) has emerged as a potential clinical entity in which selected patients may benefit from metastasis-directed local therapy in addition to systemic treatment. However, the definition of OMBC remains controversial, particularly regarding whether metastases at all anatomical sites should be considered within the oligometastatic spectrum. This study aimed to evaluate whether bladder cancer metastases at different anatomical sites respond differently to local treatment strategies and whether these metastatic sites are suitable for inclusion within the conceptual framework of OMBC.

A total of 105,554 patients diagnosed with bladder cancer between 2000 and 2021 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Clinical characteristics, metastatic patterns, treatment modalities, and overall survival were collected. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify prognostic factors in patients with metastatic bladder cancer.

Multivariate analysis showed that bone [hazard ratio (HR) 1.789, 95% confidence interval (CI): 1.680-1.904], brain (HR 1.799, 95% CI: 1.482-2.184), liver (HR 1.884, 95% CI: 1.751-2.028), and lung metastases (HR 1.825, 95% CI: 1.713-1.944) were significantly associated with overall survival, whereas distant lymph node metastases were not (HR 1.053, 95% CI: 0.983-1.127). Systemic therapy was associated with improved survival in most metastatic patients, except those with brain metastases. Chemotherapy improved survival across all metastatic sites. Radiotherapy was associated with improved survival only in patients with bone (HR 0.606, 95% CI: 0.497-0.739) or liver metastases (HR 0.820, 95% CI: 0.677-0.993). Surgery targeting distant metastatic sites did not improve prognosis, and surgical intervention for distant lymph node metastases was associated with shorter overall survival (HR 1.406, 95% CI: 1.078-1.833).

Although most patients with metastatic bladder cancer benefit from systemic therapy or chemotherapy, only patients with bone or liver metastases appear to derive benefit from targeted local radiotherapy. These findings underscore the heterogeneity of metastatic bladder cancer and suggest that the metastatic site should be considered in future research aimed at refining the definition of OMBC.