Intractable Overactive Bladder (OAB)…What next?
By Kristin Jenkins

Quebec City, Que. – When it comes to overactive bladder (OAB) does “refractory” equal “failure?”

“Refractory,” according to Dr. Roger Dmochowski, director of the Vanderbilt Continence Center, Nashville, TN, is defined by the patient’s symptoms and what she’s been exposed to, including anti-cholinergic medication.

“Many patients fail on medication because they don’t comply with dosing instructions,” Dr. Dmochowski told delegates to this year’s meeting here of Urogynecology Quebec 2007.  Dr. Dmochowski is also professor in the department of urology at Vanderbilt University Medical Center.

In evaluating “failure,” it is important to look at numerous factors involved, he said. In some patients, failure is the result of not complying with strategies such as s timed voiding. Sometimes, there are practical reasons for OAB, including a missed diagnosis of excessive fluid intake, bladder cancer or diabetes. There may also be atopine resistance related to obstruction, aging or a neurogenic condition.

When treatment for OAB fails, said Dr. Dmochowski, there are several options. They include reassurance, increasing the dose of drug or adding another drug, changing the drug or adding another type of therapy, right up to surgery.

Importantly, said Dr. Dmochowski, patients should be given the expectation of improvement rather than “cure.” Why? Because treatment doesn’t reflect the complex etiology of idiopathic OAB. “We are stuck with this shotgun approach to therapy which is obviously deficient,” noted Dr. Dmochowski.

InterStim, an “innovative” therapy described 25 years ago and approved by the FDA in 1997, is the main type of neuromodulation done in the Western world to date. Consisting of percutaneous nerve evaluation (PNE) followed by IPG and lead implantation, “We don’t really understand how it works,” said Dr. Dmochowski.

In PNE, the patient should demonstrate an objective improvement in at least one of the following:

* urge incontinence (reduction in UUI episodes)

* urge-frequency (reduction in number of voids per day; micturition volume per void; or degree of urgency prior to void).

Symptomatic improvement is common after IPG implantation, with reports of up to 76% clinical success at six months. This is defined as a 50% or more reduction in leaking episodes per day.

However, noted Dr. Dmochowski, lead migration remains one of the big problems associated with neuromodulation. Not only is this unpredictable but also it results in a dramatic return of symptoms. Device revision is common and some patients develop pain at the site or with stimulation. This treatment is also very expensive and many refractory patients do not “pass” test stimulation and thus are not candidates for implantation.

Botulinum Toxin A, the most potent biologic toxin known to man, inhibits acetylcholine release at the presynaptic cholinergic junction and results in reversible paralysis.  For OAB patients unresponsive to standard medical therapy, Botulinum toxin A or “Botox” can be injected directly into the submucosa of the bladder.

The 20-year experience with Botox indicates that it is a safe and effective treatment for OAB, although many patients become symptomatic after 6-9 months due to axonal sprouting. This is also an expensive treatment. Each treatment requires 100 to 300 units of Botox, at a cost of $420 per 100 units.

With augmentation cystoplasty, a surgical option for patients with OAB, 30% require long-term self-catheterization, a result some patients find acceptable. Long-term failure seen with this approach may be due to histologic changes, said Dr. Dmochowski.

In future, tissue engineering may be a way to augment lower urinary tract function, using biological scaffolding to address dysfunction.  And while there are many challenges to this approach, “The future may lie in these evolutions rather than in what we are doing right now,” said Dr. Dmochowski. “We need to keep our minds open to the benefits.”