5-Aminolevulinic Acid-Based Fluorescence Guidance in Urologic Oncology: Current Status, Pitfalls, and Future Directions.

5-Aminolevulinic acid (5-ALA) induces tumor-selective accumulation of protoporphyrin IX (PpIX), enabling fluorescence-guided visualization of malignant tissue. In urologic oncology, the most established application is photodynamic diagnosis (PDD) during transurethral resection of non-muscle-invasive bladder cancer, in which fluorescence can identify occult carcinoma in situ and additional papillary lesions; however, specificity may decline in the presence of inflammation, recent instrumentation, or intravesical therapy. Renal applications are emerging: oral 5-ALA before partial nephrectomy can highlight some renal tumors, but fluorescence is often heterogeneous, can overlap with normal parenchyma, and is affected by histologic subtype, necrosis, blood attenuation, and device-dependent optics. Evidence in upper tract urothelial carcinoma and prostate cancer remains preliminary, with small cohorts and practical challenges in endoscopic or robotic workflows, alongside systemic adverse events such as hypotension and photosensitivity. This review synthesizes clinical and preclinical studies of 5-ALA-based fluorescence guidance across bladder, kidney, upper tract, and prostate malignancies, focusing on where the technology is ready for practice versus where it remains investigational. We discuss common pitfalls in interpretation and implementation and outline future directions, including quantitative fluorescence and spectroscopy, standardized dosing and imaging protocols, and prospective multicenter trials linking fluorescence guidance to residual disease, recurrence, margin status, and patient-centered outcomes.