Challenges and opportunities in the management of non-urothelial bladder cancers. (2023)

• Record Type: Journal Article
• Authors: Brown, Jacqueline T.; Narayan, Vikram M.; Joshi, Shreyas S.; Harik, Lara; Jani, Ashesh B.; Bilen, Mehmet Asim
• Is Part Of: Cancer treatment and research communications. Number 34(2023)
• Publication Date: 2023
• Subjects: Non-urothelial bladder cancer -- Rare bladder cancer -- Cystectomy -- Immunotherapy -- Chemotherapy
• DOI: 10.1016/j.ctarc.2022.100663
• Languages: English
• ISSNs: 2468-2942

Abstract

Highlights: Non-urothelial bladder cancers are rare and typically excluded from enrollment in prospective clinical trials. Treatment is often extrapolated from expert opinion and retrospective data. Squamous cell carcinoma, adenocarcinoma, and small cell carcinoma of the bladder are three such non-urothelial tumors that warrant special consideration given divergence in biology and subsequent management compared to urothelial carcinoma. This review takes a comprehensive look at these three non-urothelial cancers and summarizes the literature on their management in both the localized and metastatic settings as well as future directions and ongoing clinical trial opportunities. Abstract: Urothelial carcinoma accounts for approximately 90% of all bladder cancer diagnoses. Localized, muscle-invasive disease is often managed with a multidisciplinary approach including either neoadjuvant chemotherapy (NAC) followed by radical cystectomy or concurrent chemoradiation, whereas multiple immunotherapies and novel antibody drug conjugates have recently joined platinum-based chemotherapy as standard of care therapy for metastatic disease. However, the clinical trials leading to these standards often require majority if not complete urothelial histology for eligibility. As many as one quarter of patients diagnosed with bladder cancer will have either divergent differentiation of their urothelial carcinoma or an alternate epithelial tumor such as squamous cell carcinoma, adenocarcinoma, or small cell carcinoma; even more rare are non-epithelial tumors such as sarcoma. The rarity of these diseases and their general exclusion from treatment within prospective clinical trials has created a challenging situation where treatment plans are often derived from case series or extrapolated from other disease types and outcomes are poor compared to pure urothelial carcinoma. In this review, we summarize the existing data on the diagnosis and treatment of epithelial, non-urothelial bladder cancers including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma in their localized and advances stages. We will also review the current clinical trial landscape investigating novel approaches to these diseases.