Bladder Sparing Debated at Chicago ‘Shootout’

CHICAGO—Although there has been a trend toward organ conservation in the treatment of cancer at many body sites, including the breast, head and neck, and esophagus, bladder sparing has been viewed differently, particularly in the United States.

“Radical cystectomy at the present time is still considered to be the standard of care in this country because it yields the best survival results, lowest local recurrence rates, and lowest incidence of metastatic disease,” said Donald G. Skinner, MD, professor and chairman, Department of Urology, University of Southern California Norris Cancer Center.

However, according to Anthony L. Zietman, MD, associate professor of radiation oncology, Harvard Medical School, radiation-based therapy may be useful for many of the 12,000 patients diagnosed each year with muscle-invading bladder tumors as long as the bladder-sparing approach does not inordinately delay salvage cystectomy.

Drs. Skinner and Zietman debated the role of bladder conservation therapy for transitional cell carcinoma of the bladder at the Chicago Prostate Cancer Shootout III Plus Bladder Conference, sponsored by the Chicago Urological Society, Chicago Radiological Society, and Chicago Medical Society.

The Case Against

Bladder conservation has not been routinely accepted in the United States because radical cystectomy “is exceedingly effective in preventing late recurrence and the development of metastatic bladder cancer,” Dr. Skinner said.

Based on his investigations of 1,050 bladder cancer patients treated with radical cystectomy and followed for at least 8 years, Dr. Skinner has found that patients have an 80% to 90% chance of disease-free survival at 5 years if cystectomy is performed when cancer is confined to the bladder. If the procedure is performed when cancer extends outside the bladder wall, patients have a 65% chance of being alive at 5 years with no evidence of recurrent disease.

In addition, cystectomy plus dissection of positive pelvic lymph nodes has a 30% overall 5-year survival rate, 35% if up to five nodes are positive, and 17% if six or more nodes are involved.

Bladder-sparing protocols do not yield similar results, Dr. Skinner said. Single-modality radiotherapy has a 5-year survival rate below 50% in most series. “Even when neoadjuvant chemotherapy is given before hyperfractionated radiotherapy, survival does not improve,” he said.

Most of 116 patients in an Austrian trial of bladder conservation continued to deteriorate despite 4 to 6 months of treatment with doxorubicin, cisplatin (Platinol), and radiotherapy, and one third of the patients ended up undergoing cystectomy anyway. “Bladder conservation doesn’t solve the problem,” Dr. Skinner said, “because if you leave the bladder in place, the risk of disease progression continues.” Moreover, with the addition of surgical reconstructive techniques that create continent urinary diversion, patients’ overall quality of life after radical cystectomy has improved.

“The Kock technique, which transforms a long segment of intestine into a sphere, eliminates the need for a stoma and catheter, and protects against recurring pyelonephritis, leakage, and post-procedure nephrectomy,” he said.

Dr. Zietman acknowledged that there are many legitimate concerns associated with bladder conservation: Local control is poor after radiotherapy; cystectomy, if it eventually proves to be necessary, may be inordinately delayed; bladder conservation is time-consuming and expensive; and due to high radiation doses, the bladder may be left functionally worthless. However, he pointed out that these issues can be addressed satisfactorily by adopting an approach he calls response evaluation.

The protocol involves transurethral resection of the bladder tumor followed by radiotherapy at 40 Gy, chemotherapy, and cystoscopic evaluation. Patients who have a complete response on cystoscopy receive consolidation chemoradiation and adjuvant chemotherapy. Patients who show no response undergo radical cystectomy and adjuvant therapy. All patients have routine surveillance thereafter.

A total of 162 patients were treated with this protocol at Massachusetts General Hospital (MGH) between 1986 and 1995. The majority (78%) had T2-T4 tumors. At 5 years, 54% were still alive and 42% still had their native bladder. Although 36% of the patients required cystectomy, the procedure was not excessively delayed; 35 of 58 patients had cystectomy immediately after cystoscopic evaluation revealed they had not responded completely to induction chemotherapy and radiotherapy.

Although local control of bladder cancer is uncommon after single-modality radiotherapy, the bladder conservation protocol utilized at MGH is trimodal, and at least 71% of patients have a complete response. The frequency of superficial relapse is a problem, occurring on average in 20% of the patients who have undergone bladder conservation in trials conducted by MGH, RTOG, and in Paris.

Dr. Zietman pointed out, however, that superficial recurrence is treated effectively with BCG and transurethral resection. Local control may be improved in the future by the use of accelerated radiotherapy, radiotherapy-sensitizing agents, and fluorouracil, he said.

When recurrences are not detected soon enough for salvage cystectomy, “there is the misery of uncontrolled pelvic disease,” Dr. Zietman said. The rate of total pelvic failure (including involvement of the pelvic sidewall and perirectal recurrence) after the MGH approach to bladder conservation is only about 10%, however, which is “competitive with the pelvic failure rate following radical cystectomy,” he said.

Because high doses of radiation render the bladder dysfunctional and cause bladder contraction, MGH’s bladder conservation protocol restricts the amount of radiation that is delivered. Comparatively speaking, the radiotherapy doses are lower than those given to men with prostate cancer. As a result, in the reported series, less than 2% of patients required cystectomy for bleeding or bladder contracture.

“MGH’s trimodal bladder conservation protocol admittedly is time consuming and expensive, but so is radical cystectomy,” Dr. Zietman said. “If you count the patients who have chemotherapy, radical cystectomy is not one-stop shopping.”

Not all patients with muscle-invading tumors are candidates for bladder conservation, however, such as patients with hydronephrosis who are unlikely to achieve local control. Whether bladder conservation patients lose the opportunity to receive a neobladder is debatable, he said, because creation of a neobladder is still possible after patients have received radiotherapy doses up to 40 Gy.

Although some patients receive systemic chemotherapy unnecessarily, Dr. Zietman believes this is acceptable as long as chemotherapy involves platinum, which is well tolerated. Other potential drawbacks to bladder conservation are the need for a multidisciplinary team and a motivated, compliant patient.

Dr. Zietman concluded, “For clinically staged patients, the bladder-sparing approach gives survival similar to that of cystectomy because cystectomy is not delayed very long in patients who require it. In the majority of patients, radical cystectomy is avoided, a functional bladder is maintained, and uncontrolled pelvic failure is rare.”