A Systematic Review of Intracavitary Therapies for Upper Tract Urothelial Carcinoma

BACKGROUND AND OBJECTIVE: Radical nephroureterectomy is the standard of care for management of upper tract urothelial carcinoma (UTUC), but treatment-associated morbidity is not uncommon. Intracavitary therapy has emerged as a less invasive alternative for selected cases, particularly carcinoma in situ (CIS) and low-grade papillary tumors. We conducted a systematic review to evaluate the outcomes, recurrence rates, and adverse events associated with intracavitary therapy (immunotherapy or chemoablation) for UTUC. METHODS: The review protocol was registered on PROSPERO and adhered to PRISMA guidelines. The MEDLINE, Embase, and Cochrane databases were searched in October 2024 using terms related to UTUC and intraluminal therapy. Both randomized and nonrandomized studies and single-arm studies were included. KEY FINDINGS AND LIMITATIONS: We included 11 articles reporting on nine unique studies (368 patients in total) in the review. Four studies were in upper tract CIS and five were in papillary UTUC. For CIS, Bacillus Calmette-Guérin immunotherapy resulted in a CR rate ranging from 72.7% to 100%, and a 12-mo persistent response rate of 63.6-80%. For gemcitabine-docetaxel instillation in upper-tract CIS, the recurrence-free survival rate at 12 mo was 78%. For papillary UTUC, chemoablation with mitomycin gel (UGN-101) achieved CR rates of 36.4-57.7%, with 12-mo recurrence-free survival rates ranging from 13.6% to 53.1%. Adverse events included ureteric stricture (4.5-10%), hematuria (3.1-32.8%), and loin pain (18.8-34.4%). CONCLUSIONS AND CLINICAL IMPLICATIONS: Intracavitary therapy for UTUC in the form of BCG for CIS and mitomycin C for papillary disease shows considerable efficacy, with acceptable safety profiles. These therapies represent a renal-preserving alternative for patients unfit for surgery or at high risk of renal failure, and the evidence supports their use in carefully selected patients.