HOUSTON –– Treating locally advanced bladder cancer with neoadjuvant chemotherapy –– chemotherapy before surgery –– can offer longer life to patients compared to the standard treatment of surgery alone, according to a study published in the August 28 issue of the New England Journal of Medicine.
In the 11-year study of 307 patients, conducted by the Southwest Oncology Group (SWOG) and led by an investigator at The University of Texas M. D. Anderson Cancer Center, researchers found that patients who received neoadjuvant chemotherapy lived an average of 31 months longer, and that those treated with surgery alone had a 66 percent greater chance of dying from bladder cancer 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,” says the study’s principal investigator, H. Barton Grossman, M.D., professor of urology at M. D. Anderson.
“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 says.
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 in women. According to the American Cancer Society, approximately 57,000 people are expected to be diagnosed with bladder cancer in this country in 2003 and an estimated 12,500 people will die of the disease.
Because of its tendency to spread, researchers have investigated a number of therapies to treat transitional cell bladder cancer (the most common form of the disease) which 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.
With chemotherapy proving beneficial in patients with bladder cancer that had spread to other organs, SWOG began a randomized study in 1987 testing survival in patients who received surgery alone, versus patients treated with a three cycles of a chemotherapy combination known as M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) before surgery. 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 to 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 neoadjuvant chemotherapy, according to the research team.
When overall death rates were considered –– death from any cause, not just bladder cancer –– the results were not as significant, Grossman says. After follow-up of more than eight years in each group, 90 deaths occurred in the combination therapy compared with 100 deaths in the group treated with surgery, meaning that patients who received surgery had a 33 percent greater chance of dying than patients treated with combination therapy, says Grossman. “These patients are generally older and may die of other causes, but the chance of surviving was higher in the neoadjuvant group,” he says.
Patients who did best of all were those who had no cancer left in the bladder at the time of surgery, the researchers concluded. At the time of surgery, significantly more patients (38 percent) had no evidence of cancer remaining in bladder tissue, compared to 15 percent of patients who did not have prior 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,” says Grossman. “Ten years after treatment, some of those patients are still alive, so neoadjuvant chemotherapy before surgery provided a cure for them.”
The study was supported by grants from the National Cancer Institute.