Bladder Cancer

Whole bladder photodynamic therapy with 5-aminolevulinic acid using a white light source.

Author(s): Waidelich R, Beyer W, Knüchel R, Stepp H, Baumgartner R, Schröder J, Hofstetter A, Kriegmair M.

To determine whether whole bladder photodynamic therapy after intravesical administration of 5-aminolevulinic acid using a white light source would destroy urothelial carcinoma. We sought to define the optimal target group of patients for this therapy. The side effects of treatment were also assessed. METHODS: We performed whole bladder photodynamic therapy with 100 J/cm(2) white light 2 to 4.5 hours after intravesical administration of 17% 5-aminolevulinic acid in 12 patients with recurring, multifocal, Stage pTa, grade I to III, urothelial tumors of the bladder and carcinoma in situ. RESULTS: Immediately after whole bladder irradiation, histologic examination of biopsies taken from flat suspicious lesions showed no viable cells; remnants of malignant cells were found in papillary tumors. Of the 12 patients, 11 returned for follow-up examination. At a median follow-up of 18 months (range 3 to 25), 3 of the 7 patients with carcinoma in situ and 2 of the 4 patients with papillary tumors were free of disease. In all patients, urinary frequency and urgency subsided within 3 weeks. No decreased bladder capacity or systemic side effects were observed. CONCLUSIONS: Our preliminary data show that whole bladder photodynamic therapy with intravesically applied 5-aminolevulinic acid using a white light source is effective in destroying flat malignant lesions of the bladder such as carcinoma in situ. The procedure is easy to perform and is not associated with any major side effects. The findings warrant long-term and multicenter studies.


Clinical Pharmacokinetics of 5-Aminolevulinic Acid in Healthy Volunteers and Patients at High Risk for Recurrent Bladder Cancer

Author(s): James T. Dalton, Charles R. Yates, Donghua Yin, Arthur Straughn, Stuart L. Marcus, Allyn L. Golub and Marvin C. Meyer

5-Aminolevulinic acid (ALA) is a precursor of protoporphyrin IX (PpIX) that is being evaluated for use in photodiagnosis and phototherapy of malignant and nonmalignant disorders. Previous clinical studies using topical, oral, and intravesical administration have been conducted in attempts to determine the optimal route of administration for ALA. The purpose of these studies was to examine the systemic pharmacokinetics and elimination of ALA, the bioavailability of ALA after oral and intravesical doses, and the factors that affect ALA concentrations in the bladder during intravesical treatment. The disposition of ALA was evaluated in six healthy volunteers receiving single intravenous and oral doses (100 mg) and eight patients at high risk for recurrent bladder cancer receiving an intravesical dose (1.328 g) of ALA. The mean (±S.D.) plasma area under the plasma concentration-time curve from time 0 to infinity of PpIX (0.20 ± 0.11 µg · h/ml) after intravenous administration of ALA was not significantly different from that observed after oral administration of ALA (0.15 ± 0.11 µg*h/ml; P = 0.49). ALA terminal half-life was approximately 45 min after intravenous or oral administration. The oral bioavailability of ALA was approximately 60%. After intravesical administration, urine production was largely responsible for decreases in ALA concentration in the bladder, with less than 1% being absorbed into the systemic circulation. In summary, oral and intravenous administration of ALA at these doses results in modest plasma levels of PpIX. Regional administration (i.e., intravesical) of ALA resulted in a significant pharmacokinetic advantage, with urinary bladder being exposed to concentrations approximately 20,000-fold higher than systemic circulation.


The role of photodynamic diagnosis in the contemporary management of superficial bladder cancer

Author(s): Sunjay Jain and Roger C. Kockelbergh

Photodynamic diagnosis (PDD) for bladder tumours was reported as long as 40 years ago, but the modern era was heralded with the first clinical report of the use of 5-aminolaevulinic acid (5-ALA) as a photosensitizing agent. Numerous studies have followed, most promoting the increased sensitivity that PDD offers in detecting bladder cancer. However it is still not in widespread use, perhaps because clinicians are unsure of exactly which patient groups are best served by this technique. This review will attempt to clarify, using the evidence available, where exactly PDD fits into the options available to contemporary urologists.