Urothelial Carcinoma In Situ: Advances in Diagnosis and Management

Carcinoma in situ (CIS) of the urinary tract is an aggressive, flat, high-grade form of non-muscle-invasive urothelial carcinoma, associated with a high risk of recurrence and progression. Its diagnosis remains challenging due to the absence of specific symptoms and the frequent overlap with benign inflammatory lesions. Although intravesical Bacillus Calmette-Guérin (BCG) remains the standard of care, many patients experience relapse or develop BCG-unresponsive disease, for which effective alternatives are urgently needed. Recent advances in diagnostic techniques, such as narrow band imaging and photodynamic diagnosis, have improved detection accuracy, while novel therapeutic strategies, such as immune checkpoint inhibitors, thermo-chemotherapy, intravescical gene therapy (nadofaragene firadenovec), IL-15 superagonists (eg, ALT-803), and oncolytic viral therapies (eg, CG0070), are expanding the treatment landscape. Furthermore, emerging molecular and immune-related biomarkers may help predict response to therapy and guide personalized management. This review summarizes current evidence on the biology, diagnosis, and treatment of CIS, highlighting key challenges and future directions in the effort to improve patient outcomes and reduce the need for radical cystectomy.