Fluorescence-guided local therapy for bladder and upper urinary tract cancer: a narrative review

Fluorescence-guided surgery using photodynamic diagnosis (PDD) has reshaped the local management of urothelial cancer by overcoming the limitations of white light endoscopy. Leveraging tumor-selective protoporphyrin IX accumulation after 5-aminolevulinic acid (ALA) or hexaminolevulinate (HAL) administration, PDD reliably highlights flat and subtle lesions that are frequently missed under white light, particularly carcinoma in situ. This narrative review synthesized randomized trials, patient-level meta-analyses, multicenter cohorts, and real-world studies to assess the diagnostic and therapeutic potential of PDD across the bladder and upper urinary tract. In non-muscle-invasive bladder cancer, PDD-assisted transurethral resection of bladder tumor improves resection completeness, reduces residual tumor, but its impact on recurrence remains inconsistent. In upper tract disease, integrating PDD into ureteroscopic assessment and laser ablation enhances margin definition and early oncologic control, complementing nephron-sparing strategies. Although Japanese experience with oral ALA and European experience with intravesical ALA or HAL collectively highlight the clinical utility of PDD, differences in their safety profiles, particularly in terms of the risk of hypotension associated with oral ALA administration, underscore the need for careful perioperative risk stratification. Fluorescence-guided local therapy represents a pragmatic, organ-preserving advancement in urothelial oncology and a template for the broader adoption of optical molecular guidance in cancer surgery. Thus, it serves as a bridge between molecular imaging and minimally invasive oncology.