Urothelial carcinoma is the most common type of bladder cancer including upper urinary tract urothelial cell carcinoma (renal pelvis and ureters) and urethral carcinoma. It exhibits high mortality and morbidity rates and is usually diagnosed at a late, incurable stage, carrying a poor prognosis. Local symptoms in patients with metastatic urothelial carcinoma (mUC) have an adverse impact on quality of life (QoL) and are associated with frequent hospitalizations. Herein, we review the role of palliative radiotherapy in mUC as the means to ameliorate a wide range of symptoms, seeking optimum patient stratification, even though the latter should be balanced against any acute or late toxicity that may arise. For this, links to the molecular biology of mUC are explored and QoL assessments are presented. To maximize patient benefit from radiotherapy, we conclude that multi-modal datasets need to be re-visited to better inform multi-center studies where policy makers, health professionals, researchers, and patient groups meet. Radiotherapy either as a monotherapy or alongside systemic therapy may serve as an added value.Urothelial carcinoma (UC) is considered as the most common tumor type that arises from the urinary tract and may present either as bladder carcinoma (BC), upper urinary tract urothelial cell carcinoma (UTUC), or urethral carcinoma (1). BC has been reported as the 10th most common cancer worldwide in 2020 and the 6th most common tumor type in the USA, occurring mainly in older people, with a median age at diagnosis of 73 years (2-4). In developed countries, UTUC shows a lower incidence than that of BC and the ratio of the UC incidence in the renal pelvis, ureter, and bladder is approximately 3: 1: 51 (5, 6). About 25% of patients with UC present with metastatic disease. The 5-year survival for this group of patients is only 7.7% (SEER statistics; 2, 3, 7, 8).Systemic therapy remains the cornerstone in the management of patients with mUC. Prior to the development of effective chemotherapy, median survival for mUC patients rarely exceeded 3 to 6 months (9). In the last few years, a revolution was witnessed in this field, with platinum-based chemotherapy, therapy with checkpoint inhibitors, and more recently immunotherapy, all giving promising results (10). Although the role of radiotherapy is limited in the management of mUC patients in the context of improving survival, its addition to our therapeutic toolbox offers considerable symptomatic relief especially in patients with hematuria and bone metastases (11, 12).Our aim was to feature the role of radiotherapy (RT) in mUC, emphasizing the new RT techniques available and offer guidelines on how to apply this treatment modality in different clinical scenarios. To this end, the underlying molecular enigmas and quality of life (QoL) endpoints cannot be overlooked. To maximize patient benefit from RT, either as a monotherapy or alongside systemic therapy, we conclude that multi modal datasets need to be re-visited to better inform multicenter studies where polic...