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Oncology Times:
doi: 10.1097/01.COT.0000285941.36972.8d
Article

NCCN Bladder Cancer Guidelines: Options for Chemotherapy, Organ‐Sparing Strategies

Susman, Ed

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HOLLYWOOD, FL—Doctors writing bladder cancer treatment guidelines for the 19-member National Comprehensive Cancer Network (NCCN) suggested that some evidence exists for use of organ-sparing therapy as an option for patients with higher-grade tumors.

“The most controversial area we faced on the guideline panel was how to deal with selective bladder sparing,” said the Chairman of the committee, James Montie, MD, Professor of Urologic Oncology at the University of Michigan Comprehensive Cancer Center in Ann Arbor, speaking here at the NCCN's most recent annual conference.

“Most urologists remain pretty skeptical about the widespread application of this. But it is undeniable that there is provocative data in a selected group of patients. How we select that group of patients who might respond is going to be a challenge for the future.”

Alan Pollack, MD, PhD, Chairman of the Department of Radiation Oncology at Fox Chase Cancer Center in Philadelphia, who presented the committee's thoughts on bladder-sparing therapy, said that studies appear to show that in carefully selected patients, the outcomes with bladder-sparing techniques appear to be comparable to those with radical cystectomy.

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No Consensus

“The topic of bladder preservation is indeed a controversial area,” Dr. Pollack said. “There was no consensus on the panel as to whether bladder preservation was an acceptable alternative to cystectomy. I think there are enough data to support bladder preservation in selected patients.”

Options for treatment of T2 tumors are radical cystectomy, segmental cystectomy, and selective bladder sparing, he noted. Patients who had successfully undergone a maximal transurethral resection or patients who have had a complete response to chemotherapy might be considered candidates for bladder-sparing therapy.

Strategies for treating patients after resection of the tumor include radiation therapy alone, radiotherapy combined with chemotherapy, and even transurethral resection of the bladder alone, he said.

For patients with T3-T4a tumors, options include radical cystectomy, chemotherapy, and selective bladder sparing with selection criteria similar to those for T2 grade malignancies.

“I would argue that maybe T2-T3a rather than T3-T4a is a better separation point,” he said, noting that T3-T4a tumors seem to behave differently.

“That should be kept in mind when considering bladder preservation. For very selective patients with early disease, these may be the patients who do best with bladder preservation,” he noted.

Dr. Pollack said that even for patients with T4b stage bladder tumors, there is a possibility for bladder preservation, “but as primary treatment these patients do very poorly.”

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25% Opt for Preservation

Overall, clinical studies appear to show that about 25 percent of patients with muscle-invasive bladder cancer opt for bladder-preservation therapy, and survival can be as high as 50 to 75 percent depending on tumor grade and other treatments, such as use of chemotherapy and radiation, Dr. Pollock said.

“What we have seen happen over the last several years is a movement from treatment with transurethral resection only, partial cystectomy only, or radiation only to the incorporation of chemotherapy in the treatment of muscle-invasive bladder cancer.”

In bladder cancer, chemotherapy's traditional role has been as a palliative treatment, said Gary Hudes, MD, Director of Genitourinary Malignancies at Fox Chase.

But Dr. Hudes said there are numerous areas in the guidelines where chemotherapy could fit in as data are analyzed from ongoing clinical trials evaluating double- and triple-combination chemotherapy strategies.

In palliation treatment for patients with bladder cancer metastases, caution should be used in trying multidrug treatments, Dr Hudes said.

“Patients with visceral metastases respond less often and have greater toxicity and have shorter survival with platinum-based regimens. Regimens with low toxicity are recommended for these patients in palliative treatment.”

Figure. James Montie...
Figure. James Montie...
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Figure. Gary Hudes, ...
Figure. Gary Hudes, ...
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He said studies of chemotherapy as neoadjuvant treatment show some evidence of increasing survival among cystectomy patients with T2-T3 tumors and those at high risk based on pathologic findings post-cystectomy.

“All panel members agreed that there are certain situations where adjuvant or neoadjuvant chemotherapy may be appropriate,” he said.

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Diagnosis, Treatment with Cystoscopy

Treatment of bladder cancer should actually begin at the time the urologist makes the initial cystoscopy, Dr. Montie said.

“A great deal of information is obtained from that first cystoscopy. Low-grade cancers have a very typical appearance, and essentially every urologist can identify them and then you can tailor the evaluation based on general appearance of the lesion. On the other end of the spectrum, the invasive cancers have a typical appearance. You can tell right off the bat in the office that this is going to be a bad tumor.”

Figure. Alan Pollack...
Figure. Alan Pollack...
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The initial transurethral resection of a bladder tumor should be done both as a staging procedure and as a therapeutic procedure, he said. “For many, many patients—probably the majority of patients—that is all that needs to be done, and they don't move on further down the algorithm towards more aggressive treatments.”

The NCCN guidelines call for lifetime surveillance of patients with bladder cancer, even in cases in which the likelihood of recurrence is low, he reported.

“There have been well-documented recurrences in the bladder and upper tract after prolonged disease- free intervals of even five to 10 or more years. Currently most urologists do a cystoscopy with a flexible cystoscope in the office with very minimal discomfort in men. It's not particularly pleasant, but it is no worse than sigmoidoscopy or colonoscopy.”

Industrial and research personnel are working on developing urine tests for bladder cancer detection and surveillance, but Dr. Montie said none of them have performed well enough to allow for discontinuation of flexible cystoscopy for follow-up.

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Imaging Still Required

“One other issue that has been built into the guidelines that has been controversial in the past is upper tract imaging throughout the natural history for patients who keep their bladder,” he said. “Low-grade patients have a relatively low risk of upper tract tumors, in the range of only two to four percent.”

But he said that even that low a percentage really means that the patients are at a risk that is actually 50 times greater than the normal population.

Dr. Montie said that patients with bladder carcinoma in situ have a significantly higher risk for upper-tract tumors, possibly as high as 10 to 25 percent in the five years following apparent successful treatment with Bacillus Calmette-Guerin (BCG), the attenuated strain of bovine Mycobacterium bovis used to produce an anticancer immune response.

“What we may be doing with BCG,” he suggested, “is ridding the patient's bladder of carcinoma in situ but allowing the natural history of some upper tract of prostatic-urethral disease to become evident down the line. So certainly in patients who have had carcinoma in situ, upper-tract imaging is necessary.”

© 2002 Lippincott Williams & Wilkins, Inc.

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