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Preoperative chemotherapy can improve survival for patients with locally advanced bladder cancer

Preoperative chemotherapy can improve survival for patients with locally advanced bladder cancer compared with surgical treatment alone, according to an article in the August 28th issue of the New England Journal of Medicine.

In the 11-year study of 307 patients, American researchers found that patients who received preoperative chemotherapy lived an average of 31 months longer than patients who were treated with surgery alone. In addition, patients treated with surgery alone had a 66 percent higher likelihood of bladder cancer-related mortality than patients who had the combination therapy.

"This is an important advance because the study shows a significant and clinically meaningful improvement in survival among patients who received chemotherapy before surgery," said the study's principal investigator, H. Barton Grossman, M.D. "Treatment of this disease varies across the country, but we believe neoadjuvant chemotherapy should be used more frequently to treat patients with locally advanced bladder cancer," he added.

Bladder cancer, considered a worldwide problem, is a leading tobacco-related cancer. In the United States, it is the fourth most common cancer in men and the eighth most common in women. Approximately 57,000 Americans will be diagnosed with bladder cancer in 2003 and an estimated 12,500 people will die of the disease.

Because of its tendency for local and metastatic spread, researchers have investigated a number of therapies to treat transitional cell bladder cancer that has invaded the bladder muscle and, therefore, is considered locally advanced. Studies to date have found that radiation therapy before surgery did not improve outcome.

After chemotherapy proved beneficial in patients with metastatic bladder cancer, the researchers began a randomized study in 1987 testing survival in patients who received surgery alone versus patients treated with 3 preoperative cycles of combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. The study included 126 institutions around the country.

In all, 154 patients were assigned to receive surgery as primary treatment and 153 patients received combination therapy. At the end of the study, researchers found that median survival between the two groups was significantly different. Patients treated with surgery lived a median of 41 months compared to 77 months in patients treated with chemotherapy followed by surgery.

When the investigators looked at death rates from bladder cancer, they concluded that more patients treated with surgery alone died of the disease, and they died at a faster rate -- 77 patients died of bladder cancer in the surgery arm compared with 54 in the combination treatment group. Patients treated with surgery alone had a 66 percent greater risk of dying from bladder cancer than patients who received preoperative chemotherapy.

When overall death rates were considered, the differences were not as significant, Grossman said. After follow-up of more than 8 years in each group, 90 deaths occurred in the combination therapy arm compared with 100 deaths in the surgery arm. "These patients are generally older and may die of other causes, but the chance of surviving was higher in the neoadjuvant group," he said.

The patients who did best were those who had no cancer left in the bladder at the time of surgery. At the time of surgery, 38 percent of patients treated with preoperative chemotherapy had no evidence of cancer remaining in the bladder compared with 15 percent of patients who did not receive preoperative chemotherapy.

"There were significantly more patients in the neoadjuvant group who had no residual disease compared to the surgery group and those are the patients that have much better survival. The chemotherapy effectively down-staged their cancer," noted Grossman. "Ten years after treatment, some of those patients are still alive, so neoadjuvant chemotherapy before surgery provided a cure for them."


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