Local Radiotherapy for Urinary Bladder Cancer in Patients Not Eligible for Curative Treatment

Around 700 individuals in Sweden are diagnosed each year with muscle-invasive bladder cancer (MIBC), and a similar number die annually from the disease (SVF RCC 2023). With a median age at diagnosis approaching 76 years (Swedish National Quality Registry for Urothelial Carcinoma), the incidence is expected to rise as the population ages.

Due to advanced age and comorbidity, many patients are not eligible for the demanding multimodal treatments used with curative intent. Recently introduced systemic therapies for palliation, such as antibody-drug conjugates and immunotherapy, also require a WHO performance status \<2 and regular hospital-based administration. Consequently, up to 30% of patients receive no tumor-directed therapy at diagnosis (Swedish National Quality Registry for Urothelial Carcinoma).

Without treatment, MIBC often progresses rapidly, with a median overall survival of approximately 12 months in this cohort. Symptom burden is substantial, commonly involving pain, bleeding, and urinary tract obstruction, which frequently require repeated hospital admissions late in the disease trajectory.

Radiation therapy (RT) is an established curative modality in bladder cancer and is well documented for symptom palliation. In other malignancies, such as prostate cancer, limited radiation doses have been shown to prolong survival and reduce the development of distressing symptoms. Although some studies indicate similar benefits in bladder cancer, a clear survival effect has not been demonstrated, representing an important knowledge gap in the management of a common cancer type.

The LORUP project builds on existing translational research infrastructures to address this gap. Its aim is to develop a treatment strategy for MIBC patients unfit for curative therapy, focused on improving quality of life by reducing symptom burden and potentially prolonging survival, while maintaining a low treatment burden and minimal side effects.

• Disease specific Survival [Time frame: From date of randomization until the date of death by MIBC assessed up to a minimum of 36 months]
• Progression-free survival [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to a minimum of 36 months]
• Radiological progression-free survival [Time frame: Time from randomization to the date of the first documented radiological progression or death, whichever comes first, assessed up to a minimum of 36 months]
• Start of systemic anti-tumour treatment [Time frame: Time from randomization to start of systemic anti-tumour treatment assessed up to a minimum of 36 months]
• Health related quality of life, HRQoL [Time frame: Collected every fourth month throughout follow-up from randomization to 36 months of follow-up or until death of any cause, which ever comes first]
• Patient reported outcome, PRO [Time frame: Collected at every follow up (month 1, 2 and thereafter every 4th month from randomization) until last follow-up visit at 36 months or until death of any cause, which ever comes first]
• Early adverse events /late adverse event [Time frame: Collected at every follow up (month 1, 2 and thereafter every 4th month from randomization) until last follow-up visit at 36 months or until death of any cause, which ever comes first]
• Adverse event of special interest, AESI: [Time frame: Collected throughout follow-up for a minimum of 36 months or until death of any cause, which ever comes first]