Ask the Doctor

Summer 2008

Our questions for this issue of Outlook were answered by Dr. Michael Cookson, Professor of Urologic Surgery at Vanderbilt University in Nashville, Tennessee. We sincerely appreciate his sharing his opinions and impressions with us.

Q. Many people delay having a radical cystectomy until it is far too late. Are there any guidelines for a person to use when considering when to have the surgery?

A. In patients with muscle invasive bladder cancer who are medically fit to undergo major surgery, radical cystectomy remains a gold standard treatment option offering unparalleled local cancer control and cure when the tumor is contained within the specimen. While the decision to proceed with cystectomy for muscle invasive disease is not controversial, there is debate as to the timing of the surgery. Specifically, there has been an increasing awareness of the fact that delay in the cystectomy may result in more advanced pathologic staging as compared to those who undergo surgery in a more timely fashion. Most importantly, a delay of more than 3 months from the time of diagnosis to cystectomy has in some studies resulted in a worse cancer-specific survival as compared to those who undergo cystectomy earlier.

It is important to note, however, the limitations of some of these studies, as they may not address the reasons for delay (e.g. additional cardiac or pulmonary testing might be necessary). In addition, these studies do not address the role of neoadjuvant chemotherapy which has been associated with improved survival in patients with locally advanced tumors and may take up to three months to administer prior to surgery. Furthermore, these studies do not address the delay that may occur from the onset of symptoms such as hematuria until the referral to a urologist who performs the tests to determine whether the patient has bladder cancer. What is known, however, is that invasive bladder cancers are often aggressive and unnecessary delay in diagnosis or from the time of diagnosis until definitive treatment is often associated with worse outcomes. So, the take home message for patients is to not delay in notifying your physician if you are experiencing symptoms that may be related to the discovery of a bladder cancer. For patients with non-muscle invasive bladder cancer (NMIBC), the timing of cystectomy presents a more difficult situation. In this scenario in which the bladder tumor is not invading the muscle but is recurring and threatening to progress despite aggressive resection and intravesical therapy, there is a general reluctance by patient and clinician alike to remove the bladder. While all options for intravesical therapy including chemotherapy and immunotherapy (BCG) are beyond the scope of this article, suffice it to say that most patients who have recurrent high grade Ta, T1 (lamina propria involvement) or CIS 6 months after either two 6-week courses of BCG or maintenance BCG are at significant risk for tumor progression to invasive disease which could result in death from disease.

In summary, patients with muscle invasive bladder cancer should undergo prompt consideration for radical cystectomy. Once the decision is made, the surgery should be performed without unnecessary delay. Best outcomes are reported if the cystectomy is performed within 3 months of the diagnosis. This in no way should deter physicians or patients from important preoperative evaluations and/or second opinions regarding decision-making. Among patients with high-risk NMIBC, failure or recurrence after two-six week courses or maintenance BCG may be an indication for cystectomy. However, if salvage intravesical therapy is attempted, patients need to be followed closely to ensure that they are not progressing. Among patients with NMIBC, timely radical cystectomy should be considered an option in the setting of failed intravesical therapy.

Q. In terms of urinary diversions, aside from what is readily available today, are there any viable alternatives on the near horizon?

A. The past decade has seen significant advancements in bladder tissue engineering research, with the anticipation that it will ultimately provide functional tissue substitutes to replace diseased or dysfunctional tissues including bladder cancer. There have been some early reports of success with bladder augmentations and grafts using these techniques but to date there have been no attempts to use these methods in patients with bladder cancer requiring cystectomy. At present, the consensus is that progress being made towards bio-engineered bladders becoming a clinical reality once unresolved research and translational issues have been addressed. Currently, for patients undergoing cystectomy for bladder cancer there is no readily available substitute for bowel and there are no currently available artificial or synthetic bladders. For the foreseeable future, surgical improvements have been directed at laparoscopic and robotic-assisted radical cystectomy that may afford diversion via a smaller incision reduced convalescence and possibly improved functional outcomes. This is currently an evolving area of surgical research and will require performance in larger numbers of patients and longer follow-up before definitive conclusions can be made. However, the ideal bladder substitute remains elusive and the best current substitute regardless of choice of diversion is the patient’s own small or large intestine.