A Systematic Review of Novel Intravesical Approaches for the Treatment of Patients with Non-muscle-invasive Bladder Cancer

BACKGROUND AND OBJECTIVE: Intravesical therapy is central to managing non-muscle-invasive bladder cancer (NMIBC); yet, recurrence and progression remain common, underscoring the need for new treatments. This systematic review evaluates clinical trials of novel intravesical therapies for all risk categories of NMIBC.

METHODS: A comprehensive literature search was conducted to identify the clinical trials assessing the effectiveness, safety, and tolerability of intravesical therapies for NMIBC. The search focused on studies published from 2020 to 2024, including trials on bacillus Calmette-Guérin (BCG)-unresponsive/refractory disease as well as on BCG-naïve and intermediate-risk patients. Mechanisms of action and drug delivery methods were summarized. No statistical syntheses were performed due to limited comparative data.

KEY FINDINGS AND LIMITATIONS: Out of 2998 studies identified, 36 reported on efficacy and safety, and six provided patient-reported outcomes (PROs). Intravesical therapies included BCG-based therapies, chemotherapy combinations, chemical-drug conjugates, thermogels, hyperthermic chemotherapy, osmotic pumps, and gene therapy. Initial response rates ranged from 42% to 85% for BCG-unresponsive/refractory patients and from 65% to 100% for treatment-naïve patients. The 12-mo recurrence-free survival rates ranged from 22% to 83% and 39% to 92%, respectively. Progression and severe toxicity (grade ≥3) were rare (0-17% and 0-20%, respectively). PROs were stable. The limitations included early-phase studies, heterogeneous outcome assessments, and a need for research on long-term durability, comparative effectiveness, quality of life, and cost.

CONCLUSIONS AND CLINICAL IMPLICATIONS: This systematic review highlights the promising efficacy and tolerability of novel intravesical therapies for NMIBC. However, further research is needed to refine treatment strategies and assess long-term outcomes, quality of life, and economic factors. Future studies should include multiarm, multistage designs with a focus on patient-centered outcomes.