Time to metastasis predicts prognosis and improves the Bellmunt score in metastatic urothelial carcinoma

Abstract Prognostic models for metastatic urothelial carcinoma (mUC) have limited accuracy and additional clinically meaningful factors are needed to improve risk stratification. Time to metastasis from initial diagnosis (TTM) is an established prognostic variable in other urologic malignancies; however, its significance in mUC has not been fully defined. We conducted a retrospective multicenter study of 388 patients with mUC who received first-line platinum‑based chemotherapy to evaluate the prognostic impact of TTM and to develop a modified risk model incorporating this factor. Patients were categorized as having synchronous (TTM < 6 months) or metachronous (TTM ≥ 6 months) metastasis. Overall survival (OS) was the primary endpoint. In the multivariate analysis, liver metastasis, hemoglobin levels < 10 g/dL, and synchronous metastasis were independent predictors of shorter OS. Incorporating TTM into Bellmunt score significantly improved prognostic performance, increasing the C‑index from 0.575 to 0.613. Time‑dependent analyses demonstrated superior C‑indices for the modified scores at 12 and 24 months, and decision curve analysis showed a greater net clinical benefit. Net reclassification improvement was also significant, driven primarily by the event‑NRI. These findings indicate that TTM is an independent prognostic factor and that its incorporation enhances the clinical utility of Bellmunt score for risk stratification in mUC.