Oral 5-aminolevulinic acid in simultaneous photodynamic diagnosis of upper and lower urinary tract transitional cell carcinoma - a prospective audit

Ahmad, Sarfraz, Aboumarzouk, Omar, Somani, Bhaskar, Nabi, Ghulam and Kata, Slawomir Grzegorz (2012) Oral 5-aminolevulinic acid in simultaneous photodynamic diagnosis of upper and lower urinary tract transitional cell carcinoma - a prospective audit. BJU International, 110 (11 Pt B), E596-600. (doi:10.1111/j.1464-410X.2012.11326.x).

Abstract

The idea of using photosensitizing agents to enhance visualization of cancer tissue dates back to 1900. 5-Aminolevulinic acid (5-ALA) was first suggested for photodynamic diagnosis (PDD) of transitional cell cancer (TCC) of the bladder in 1992. Since then, PDD with intravesical application of 5-ALA or its ester hexaminolevulinate (Hexvix) has proven to be superior over standard white-light cystoscopy in detection of carcinoma in situ and dysplasia as well as enhancing margins of TCC. PDD of upper urinary tract TCC is under-studied because of trouble with delivery of the photosensitizer. Fluorescence after oral 5-ALA was initially reported in 1956. Oral 5-ALA for photodynamic therapy was suggested for upper urinary tract TCC in 1998 and for refractory non-muscle invasive bladder cancer in 2001. A study in 2012 on oral and intravesical application of 5-ALA for bladder PDD showed no difference in diagnostic accuracy for each modality. To our knowledge our series is the first report on use of oral 5-ALA for PDD in detection of upper urinary tract tumours. We published our initial results in 2010. We think that our recent audit is quite encouraging. PDD ureterorenoscopy resulted in detection of additional urothelial tumours that could have been missed by the conventional white-light endoscopy. We suggest that this technique should be used in large multicentre trials to replicate our results.

Objective: to evaluate the diagnostic accuracy of photodynamic diagnostic ureterorenoscopy after oral administration of 5-aminolevulinic acid (5-ALA) for upper urinary tract urothelial cancers.

Patients and methods: in this audit, twenty-six patients underwent thirty-nine procedures (cystoscopy/ureterorenoscopy) following oral administration of 5-ALA for photodynamic diagnosis (PDD). • Twenty mg/kg body weight of 5-ALA was given orally 3-4 hours prior to the planned endoscopic visualisation. • Following standard white light cystoscopy and ureterorenoscopy, photodynamic diagnostic endoscopy was performed using D-light system (Olympus PDD cystoscope and 7.5Fr KARL STORZ PDD Flex-X ureterorenoscope) to detect fluorescence. • Biopsies were carried out from all suspicious areas, noting if lesions were detected under white or blue light or both.

Results: a total of sixty-two biopsies were performed for suspicious urothelial lesions (35 bladder, 26 ureter/renal pelvis and 1 from prostatic urethra). • Of the 35 bladder biopsies, 11 lesions were seen under both white and blue light and 91% of these were malignant. • While 24 (68.5%) biopsies were taken from lesions seen only under blue light and 45.8% of these were malignant. • Similarly, of the 26 ureteric/renal pelvicalyceal biopsies, 11 were concurrent in both white and blue light and 100% of these were malignant. • While 10 (38.5%) lesions were seen only under blue light and 70% of these were malignant.

Conclusions: photodynamic diagnosis using oral 5-ALA is safe and feasible with additional advantages of detecting lesions not visualised with conventional white light endoscopy. • This may translate into more complete treatment thereby decreasing subsequent recurrences and possibly progression of the upper urinary tract urothelial cancers.

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