Combination cancer therapy salvages bladder.

An experimental approach to invasive bladder cancer may spare the bladder yet save the patient.

For the past 20 years, surgeons have treated such malignancies by removing the entire bladder. Although that traditional approach results in a 50 percent survival rate after five years, patients must live with the discomfort of urine-collecting bags that never quite work the way a healthy bladder does.

Oncologist Donald S. Kaufman and his colleagues at the Massachusetts General Hospital in Boston didn't want to jeopardize their patients' survival, but they did want to avoid radical surgery if possible. So they devised a regimen designed to preserve the bladder while launching a blitz on the cancer.

This year, an estimated 52,300 people in the United States will develop bladder cancer. About 30 percent of that group would be candidates for the experimental regimen, Kaufman estimates.

The Boston team recruited 53 people with invasive bladder cancer, in which the disease has spread to the bladder's muscular wall. All 53 then underwent a procedure called transurethral resection, in which surgeons guide a slender fiberoptic scope through the urethra to the bladder. Aided by a video display of the bladder's interior, surgeons then manipulate tiny instruments to remove the tumor. Afterwards, patients received an initial blast of several different types of chemotherapeutic drugs, as well as radiation therapy.

For patients who showed any signs that their cancers had not responded, the team recommended complete removal of the bladder, the traditional operation known as radical cystectomy. Rather than risk a recurrence of cancer, eight patients opted for this operation.

In 34 cases, patients either responded well to early therapy or couldn't tolerate such a drastic operation. They went on with the experimental treatment, which consisted of more chemotherapy and radiation, the researchers report in the Nov. 4 NEW ENGLAND JOURNAL OF MEDICINE.

Eleven other patients couldn't complete the experimental regimen. Some couldn't tolerate the harsh chemotherapy or radiation therapy, and others refused to undergo a radical cystectomy when doctors advised such a course.

Overall, out of the 53 patients studied, 28 (53 percent) were alive after about four years, when a follow-up examination was conducted. In addition, 24 of the 53 (45 percent) showed no visible evidence of a recurring tumor, the researchers note.

Of the 34 who completed the experimental protocol, 28 tolerated the full doses of chemotherapy and radiation. Of these, 25 (89 percent) remained free of bladder cancer, the team reports. These patients all had the added bonus of a functioning bladder, Kaufman points out.

Overall, the results of this pilot study suggest that this attempt to spare the bladder compares favorably with the surgeon's knife. Yet Kaufman points out that the study didn't include a control group and thus the survival statistics might be influenced by an unknown bias.

These results may force oncologists and surgeons to reevaluate their approach to invasive bladder cancer, comments oncologist Howard I. Scher of the Memorial Sloan-Kettering Cancer Center in New York City. The findings argue against "the automatic reaction of many people, which is to just remove [any] bladder with signs of muscle invasion," Scher says.

In the future, doctors may base their decisions about a bladder cancer regimen on the tumor's molecular characteristics, Scher adds. People with highly aggressive tumors may get a cystectomy, whereas others will start with a bladder-salvaging approach. Scher wrote an editorial that appears in the same issue.

Meanwhile, the Boston researchers continue to monitor their patients. Will some of these same people remain cancer-free for eight years or longer? "All I can say is that I'm hopeful," Kaufman says.