Radiotherapy in Metastatic Urothelial Carcinoma: Rationale and Clinical Applications

Abstract

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...

Upper Tract Urinary Carcinoma: A Unique Immuno-Molecular Entity and a Clinical Challenge in the Current Therapeutic Scenario

“…Among other therapeutic approaches, the role of RT is still marginal, both in metastatic BC and UTUC, being administered mostly with a symptomatic/ palliative intent. 97 The current evidence supports the use of RT to rapidly and effectively minimize tumor-induced urinary symptoms, such as hematuria, and demonstrates a similar symptom improvement following hypofractionated palliative RT compared to multifractionated treatments. 97 In addition, as reported by a recent Japanese study, in a selected patient population, consolidative RT (usually more than 50 Gy) may result in long-term disease control and improved quality of life.…”

“…97 The current evidence supports the use of RT to rapidly and effectively minimize tumor-induced urinary symptoms, such as hematuria, and demonstrates a similar symptom improvement following hypofractionated palliative RT compared to multifractionated treatments. 97 In addition, as reported by a recent Japanese study, in a selected patient population, consolidative RT (usually more than 50 Gy) may result in long-term disease control and improved quality of life. 98 Finally, although based on a small number of observations, a potential role of stereotactic body radiation therapy in specific cases of oligometastatic UC displaying distant node metastases, has been advised.…”

Efficacy of Combined Pembrolizumab and Pelvic Radiotherapy for Bladder Cancer With Rectal Metastases

“…Before treatment, anal pain was approximately 7/10 on the Numerical Rating Scale (NRS) even with tramadol hydrochloride and acetaminophen; however, after treatment, the NRS score was reduced to 2/10 without the use of analgesics. Vassiliou et al concluded that RT has the potential to synergize with immunotherapy to improve oncological outcomes in patients with localized or metastatic bladder cancer, and Palliative RT in the form of external beam irradiation in combination with chemotherapy, targeted therapies and, more recently, immunotherapy, offers palliation and relief from symptoms (13).…”

N6-methyladenosine (m6A) reader IGF2BP1 facilitates clear-cell renal cell carcinoma aerobic glycolysis

“…More precisely, clear cell renal cell carcinoma (ccRCC) is a higher invasive subtype of RCC, comprising 80–90% of RCC patients ( Liu et al, 2022b ; Pei et al, 2022 ). Unfortunately, the chemotherapy or radiotherapy is largely ineffective for all renal cancer subtypes ( Vassiliou et al, 2022 ; Yin & Zheng, 2022 ). Therefore, the immunotherapy or targeted therapy is a very valuable alternative strategy.…”