Stage IVA/IVB urothelial bladder cancer (UBC) has a historically poor prognosis. With the rapid evolution of systemic therapies, establishing real-world outcomes from the preceding era is critical. We aimed to define treatment patterns, survival, and prognostic factors in a large single-center cohort, providing a benchmark against which modern advances can be measured.
We retrospectively reviewed patients with Stage IVA/IVB UBC who initiated first-line systemic therapy between January 2010 and December 2022. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods. Multivariable Cox models identified independent prognostic factors.
A total of 159 patients (Stage IVA, n = 60; Stage IVB, n = 99) were included, with a median age of 69 years and 75% male. After a median follow-up of 86.2 months for survivors, median OS was 23.0 months for Stage IVA versus 7.4 months for Stage IVB (p<0.001). Response rates were 53.3% and 18.2%, respectively. Among Stage IVA patients, a multimodality approach incorporating radical cystectomy was associated with favorable long-term survival in a highly selected subgroup, with a median OS of 65.0 months. In propensity score-weighted analysis, median OS was 54.0 months for the surgical group versus 14.0 months for systemic therapy alone (p < 0.001). On multivariable analysis, poor ECOG performance status (3-4) independently predicted worse OS (HR 2.70, p = 0.012).
Survival in Stage IV UBC differs markedly by substage. Selected Stage IVA patients may achieve long-term survival with aggressive multimodal therapy including cystectomy. These outcomes provide a historical benchmark, highlighting the impact of novel therapies.
Clinical genitourinary cancer. 2026 Mar 16 [Epub ahead of print]
Ali Mushtaq, Emily C Zabor, Bridget Adcock, Aastha Dhakal, Naveen Rehman, Muaz Alsabbagh Alchirazi, Moath Albliwi, Hadil Zureigat, Monica Lee, Ahmed Nabil Mohamed Hassan, Heya Batah, Preeyal Patel, Meera Patel, Sara F Haddad, Nicole Vincek, Moaath Khader Mustafa Ali
Department of Internal Medicine, Cleveland Clinic, Cleveland, OH., Department of Quantitative Health Sciences, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address: .