Photodynamic Therapy in Bladder Cancer Management: Integrated Innovations and Clinical Translation

Despite Bacillus Calmette-Guérin therapy, non-muscle invasive bladder cancer (NMIBC) has 60-70% recurrence rates, necessitating bladder-preserving strategies. Photodynamic therapy (PDT) advances through: (1) Third-gen photosensitizers (e.g., Ce6-PVP) showing 89% 1-year recurrence-free survival in Phase III trials via pH-responsive tumor targeting (tissue ratio 23:1); (2) Nanocarriers (e.g., folate-targeted Au@TNA) achieving >95% pathologic complete responses in BCG-unresponsive cases; (3) PDT-PD-L1 combinations increasing CD8+ T-cell infiltration 4.3-fold, attaining 94% complete remission in carcinoma in situ. Safety profiles reveal <3% severe adverse events (vs. 6.8% chemotherapy) with 84% cystectomy avoidance. Emerging innovations include glutathione-responsive activatable PSs (NCT05246774) and AI-driven light dosing. These developments establish PDT as a pivotal organ-sparing therapy for NMIBC.