Cretostimogene Grenadenorepvec

Non-muscle-invasive bladder cancer (NMIBC) accounts for roughly 75% of newly diagnosed bladder cancer and associates with high risk of recurrence and progression. Intravesical therapy remains the cornerstone of NMIBC management following transurethral resection of bladder tumor (TURBT). For low-risk NMIBC, immediate single instillation of chemotherapy after TURBT effectively reduces recurrence. Intermediate-risk patients could benefit from either intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) instillation, with emerging therapies such as UGN-102 chemoablation showing promise. For high/very high-risk NMIBC, full-dose, 3-year BCG instillation remains the standard of care, However, global BCG shortages and treatment failures have prompted the need for alternative strategies. Optimization of BCG regimens, such as two induction courses, may preserve efficacy while improving feasibility. Moreover, alternative agents such as sequential gemcitabine and docetaxel instillation have demonstrated favorable outcomes in both BCG-naïve and BCG-unresponsive patients. For those with BCG failure, a number of novel therapies are under active investigation. Gene therapy (nadofaragene firadenovec), oncolytic viral therapy (CG0070), interleukin-15 superagonist (Nogapendekin alfa-inbakicept), and innovative drug delivery systems (TAR-200) have shown encouraging clinical potential in this population. This review provides an overview of current intravesical treatment strategies for NMIBC across different risk groups and highlights promising new approaches aimed at overcoming the limitations of BCG therapy.

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.