As a result, a substantial number of patients with MIBC do not receive curative-intent treatment due to concerns related to potential morbidity and quality-of-life changes from urinary diversion. Chemoradiation therapy (CRT) has emerged as an important bladder-preserving alternative, with pooled analyses of clinical trials reporting five-year CSS rates of approximately 71%.1 However, these results largely derive from select patients treated at high-volume academic centers, with older adults and those with greater comorbidity burden underrepresented, resulting in poor characterization of population-based CRT outcomes.
To address this gap, we designed an observational study using SEER-Medicare data based on the control arm of the SWOG/NRG 1806 trial, a contemporary randomized trial evaluating CRT with or without atezolizumab in MIBC.2 By applying target trial emulation principles described by Hernán and Robins, we aimed to describe high-fidelity population-based outcomes of CRT.3
Our study identified 283 patients aged 66–89 years (median age 78) treated with CRT for cT2–T4a N0 M0 urothelial bladder cancer from 2000 to 2017. The majority had T2 disease (87%) and received cisplatin-based concurrent chemotherapy (74%). The five-year CSS was 53%, and overall survival (OS) was 35%. The observed survival rates are notably lower than the 71% CSS and 57% OS reported in pooled trial data.1
Although these findings suggest that CRT performed in non-trial settings may be associated with worse oncologic outcomes than reported in seminal trials, caution must be employed when making such interpretations, as observed differences may be due to several factors. First, differences between trial and non-trial populations may contribute to the observed outcome differences. In addition, methodological limitations related to SEER-Medicare preclude complete specification of CRT protocols as utilized in seminal trials, including radiation therapy dosing and delivery, timing of concurrent chemotherapy administration, and treatment completeness, as well as identifying palliative-intent chemoradiation regimens. Finally, differences in clinical staging between real-world and trial settings may also contribute, with occult higher-stage disease potentially misclassified as T2 in administrative data.
Among the prognostic factors we examined, female sex was independently associated with an increased risk of cancer-specific mortality, consistent with emerging data suggesting sex-based differences in response to trimodality therapy.4 This finding warrants further investigation, as it may reflect differences in stage at presentation, tumor biology, or treatment response. We also observed that lower neighborhood education level was independently associated with worse cancer-specific and overall survival, which is consistent with prior literature linking lower socioeconomic status to disparities in cancer care access, treatment at high-volume centers, and stage at diagnosis.5
Collectively, our findings highlight the need for prospective studies and ongoing population-based monitoring of CRT outcomes in older adults. As CRT utilization grows due to positive findings from recent trial data and advances in immunotherapy, understanding the gap between trial efficacy and real-world effectiveness will be essential to optimizing outcomes for patients undergoing bladder-preserving treatment.6
Written by: Piroz Bahar and Boris Gershman, MD
- Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
- Mak RH, Hunt D, Shipley WU, et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014;32(34):3801–9.
- SWOG/NRG S1806. Randomized phase II/III trial of chemoradiotherapy with or without atezolizumab in localized muscle-invasive bladder cancer. ClinicalTrials.gov identifier NCT03775265.
- Hernán MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol. 2016;183(8):758–64.
- Ballas LK, Navarro S, Luo C, et al. Disparities in male versus female oncologic outcomes following bladder preservation: a population-based cohort study. Cancer Med. 2021;10(9):3004–12.
- Cheng E, Soulos PR, Irwin ML, et al. Neighborhood and individual socioeconomic disadvantage and survival among patients with nonmetastatic common cancers. JAMA Netw Open. 2021;4(12):e2139593.
- Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, Atduev V, Göger YE, Rausch S, Kang SH, Loriot Y, Bedke J, Galsky MD, O'Donnell PH, von Amsberg G, Alimohamed N, Sulimka G, Gupta S, Paramonov V, Nakane K, Mihm M, Meng C, Huang CD, Ramamurthy C, Homet Moreno B, Ullén A; KEYNOTE-905/EV-303 Investigators. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Feb 18. doi: 10.1056/NEJMoa2511674. heng E, Soulos PR, Irwin ML, et al. Neighborhood and individual socioeconomic disadvantage and survival among patients with nonmetastatic common cancers. JAMA Netw Open. 2021;4(12):e2139593.