The Management Of BCG Failure In Non-muscle-invasive Bladder Cancer: An Update

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 14 Jun 2010 - 0:00 PDT


UroToday.com - A major dilemma among patients with non-muscle-invasive bladder cancer (NMIBC) and their physicians is the choice of an appropriate course of action following failure of intravesical bacillus Calmette-Guerin (BCG). Although classified the same, NMIBC actually consists of 2 biologically different diseases; 1) low-grade NMBIC who are likely to recur but rarely progress and 2) high-risk T1 bladder cancer and/or carcinoma in situ (CIS or TIS) which often progresses to an aggressive muscle-invasive life threatening disease.

Approximately 30-40% of patients do not respond to BCG therapy signifying that treatment options should be customized between these 2 patient types. Urologists commonly administer BCG as a first-line therapy in low-grade disease with BCG failure carrying a risk of recurrence and rarely progression. A set treatment regime for patients with high-grade non-muscle invasive T1 disease remains to be determined. Controversy exists over immediate cystectomy or administration of BCG.

Immediate cystectomy offers the best chance for survival but is often associated with impaired quality of life. In addition, factors such as patient age, comorbidity and individual preference also play a factor. BCG responders, on the other hand, retain their bladder and are spared cystectomy complications maintaining their quality of life. However, there is a chance of BCG failure and the narrow window of curability may be lost.

There have been several factors that explain BCG failure such as 1) insufficient or excess BCG affecting the efficacy of the immune response; 2) premature evaluation; 3) under appreciating occult invasive or metastatic disease; 4) failure of BCG contact with the target. In addition, there have been tremendous efforts in defining BCG failure and when to abandon BCG in favour of another strategy. The Canadian Guidelines for Treatment of Non-Muscle-Invasive Bladder Cancer have defined BCG failure.

While guidelines provide a good definition of BCG failure, unfortunately BCG failure cannot be accurately predicted on an individual basis. Nevertheless, with clinical and histologic parameters, risk groups should be identified because the window of curability in patients with BCG failure is narrow in the case of tumour progression to muscle-invasive cancer. Such window should be immediately targeted if possible for optimal outcome, either with conservative treatments with immunotherapy or with cystectomy.

Immunotherapy agents include agents such as Urocidin, interferon-α and Vicinium. Risk factors include presence of CIS, early recurrence, recurrent vs. progressive tumor, T1 substage and gender. For patients with CIS or high-risk tumors failing BCG, the guidelines recommend cystectomy as the treatment of choice. However, cystectomies are often associated with impaired quality of life compared with conservative therapy. Thus, it remains necessary for the clinical research community to identify new methods where patients are able to keep their bladders while simultaneously keeping their tumors under control.

Written by Alexandre R. Zlotta, MD, FRCSC as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

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