ANAHEIM, CA (UroToday.com) - Dr. Michael O'Donnell presented a State-of-the-Art lecture "Novel Treatment Approaches to Superficial TCC" at the Tuesday Plenary Session of the AUA in Anaheim, May 22, 2007.

He began by showing the EORTC risk stratification tables for non-invasive bladder cancers. Dr. O'Donnell showed the 12% absolute reduction in TCC recurrence with a single dose of post-TUR intravesical chemotherapy. This is part of the EAU guidelines and he hopes it will be endorsed by the AUA. He talked about the importance of re-resection for T1 bladder cancer. In up to 25-50% of cases, there will be upstaging to T2 disease.

Regarding chemotherapy, MMC effectiveness is improved when it is more concentrated and used in a dehydrated patient to avoid dilution in the bladder. Alkalinization of the urine also helps. Microwave chemothermotherapy consists of a microwave catheter with circulating chemotherapy. This looks promising, he said. BCG maintenance is important for reducing risk of disease progression and to improve outcomes over MMC. However, the best regimen is not known. Tolerability of BCG is improved using dose reduction (30-50% decreased toxicity). Decreasing dwell time and slow-rate dosing (giving it every other week) help as well. Giving the fluorquinolone antibiotic ofloxacin after therapy reduced the toxicity in one study.

Combining BCG with IFN for refractory patients improves outcomes, likely by a synergistic suppression of IL-10. A 60% CR rate was found in BCG naïve patients and 44% in BCG failures. BCG plus IFN should not be used in those with 2 BCG related failures, as they are not very effective. Gemcitabine has a favorable toxicity and a different mechanism of action. However, the only study that looked at it in the salvage setting showed only a 7% durable CR. In a study performed at Columbia University, intravesical docetaxel for BCG failures demonstrated a 33% CR rate at 14 months. He said that non-vesicant agents may demonstrate higher tolerability and efficacy and this is under investigation. This would include combinations using adriamycin, gemcitabine, docetaxel, and mitomycin, for example.

Two groups have reported gene therapy strategies. One is using adenoviral IFN gene therapy. It results in strong IFN presence in the bladder over 7 days. The second is replication competent GMCSF adenovirus with preferential expression in Rb altered cells. This is presently in clinical trial. A variety of other novel agents are presently underdevelopment.

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Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

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