Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development
Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies...
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| author | Whi-An Kwon Ho Kyung Seo Geehyun Song Min-Kyung Lee Weon Seo Park |
| author_facet | Whi-An Kwon Ho Kyung Seo Geehyun Song Min-Kyung Lee Weon Seo Park |
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| description | Urothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-d89cc12396154bedbc4487ecc466a4d32025-01-24T13:23:58ZengMDPI AGBiomedicines2227-90592025-01-011318610.3390/biomedicines13010086Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current DevelopmentWhi-An Kwon0Ho Kyung Seo1Geehyun Song2Min-Kyung Lee3Weon Seo Park4Department of Urology, Myongji Hospital, Hanyang University College of Medicine, Goyang-si 10475, Republic of KoreaDepartment of Urology, Center for Urologic Cancer, National Cancer Center, Goyang-si 10408, Republic of KoreaDepartment of Urology, Center for Urologic Cancer, National Cancer Center, Goyang-si 10408, Republic of KoreaDepartment of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang-si 10475, Republic of KoreaDepartment of Pathology, National Cancer Center, Goyang-si 10408, Republic of KoreaUrothelial carcinoma (UC) is the most common histological subtype of bladder tumors; however, bladder cancer represents a heterogeneous group of diseases with at least 40 distinct histological subtypes. Among these, the 2022 World Health Organization classification of urinary tract tumors identifies a range of less common subtypes of invasive UC, formerly known as variants, which are considered high-grade tumors, including squamous cell, small-cell, sarcomatoid urothelial, micropapillary, plasmacytoid, and urachal carcinomas, and adenocarcinoma. Their accurate histological diagnosis is critical for risk stratification and therapeutic decision-making, as most subtype histologies are associated with poorer outcomes than conventional UC. Despite the importance of a precise diagnosis, high-quality evidence on optimal treatments for subtype histologies remains limited owing to their rarity. In particular, neoadjuvant and adjuvant chemotherapy have not been well characterized, and prospective data are scarce. For advanced-stage diseases, clinical trial participation is strongly recommended to address the lack of robust evidence. Advances in molecular pathology and the development of targeted therapies and immunotherapies have reshaped our understanding and classification of bladder cancer subtypes, spurring efforts to identify predictive biomarkers to guide personalized treatment strategies. Nevertheless, the management of rare bladder cancer subgroups remains challenging because they are frequently excluded from clinical trials. For localized disease, curative options such as surgical resection or radiotherapy are available; however, treatment options become more limited in recurrence or metastasis, where systemic therapy is primarily used to control disease progression and palliate symptoms. Herein, we present recent advances in the management of urothelial and non-urothelial bladder cancer subtypes and also explore the current evidence guiding their treatment and emphasize the challenges and perspectives of future therapeutic strategies.https://www.mdpi.com/2227-9059/13/1/86antibody–drug conjugatesbladder cancerchemotherapyFGFR inhibitorsimmunotherapynon-urothelial cancer |
| spellingShingle | Whi-An Kwon Ho Kyung Seo Geehyun Song Min-Kyung Lee Weon Seo Park Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development Biomedicines antibody–drug conjugates bladder cancer chemotherapy FGFR inhibitors immunotherapy non-urothelial cancer |
| title | Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development |
| title_full | Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development |
| title_fullStr | Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development |
| title_full_unstemmed | Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development |
| title_short | Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development |
| title_sort | advances in therapy for urothelial and non urothelial subtype histologies of advanced bladder cancer from etiology to current development |
| topic | antibody–drug conjugates bladder cancer chemotherapy FGFR inhibitors immunotherapy non-urothelial cancer |
| url | https://www.mdpi.com/2227-9059/13/1/86 |
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