New research from the Southwest Oncology Group (SWOG) shows that patients who undergo surgery for bladder cancer could significantly improve their chances for survival if they receive chemotherapy first.
In a clinical trial involving 307 patients with locally advanced bladder cancer, patients given chemotherapy plus radical cystectomy surgery had a median survival of 77 months compared to 46 months for those who were treated with surgery alone.
The enhanced survival of those who received combination therapy correlated with the absence of detectable cancer in the muscle tissue of the bladder at the time of surgery.
Dr. Catherine Tangen, an investigator in the Public Health Sciences Division, co-authored the study, which appears in the Aug. 28 issue of the New England Journal of Medicine. The study was lead by Dr. H. Barton Grossman at the M.D. Anderson Cancer Center in Houston and involved researchers at nine other institutions and participants at 126 hospitals. Tangen is a biostatistician in SWOG's statistical center, which is housed jointly within the PHS Division and Cancer Research and Biostatistics, a Seattle nonprofit company.
Tangen said that the 11-year study should help to resolve some of the controversy about the value of adding a chemotherapy regimen to radical cystectomy surgery.
"There have been a lot of conflicting studies involving many different chemotherapy regimens used either before (neoadjuvant) or after (adjuvant) cystectomy," she said. "In the past, it's been difficult for both doctors and patients to consider adding chemotherapy to what is a very debilitating surgical procedure. But this study provides compelling evidence that patients can significantly improve their survival, and that the chemotherapy is well tolerated. It gives us a good starting point to begin other studies of regimens that may have even fewer side effects than the drugs used in this clinical trial."
Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women in the United States. The American Cancer Society estimates that this year, 57,400 new cases of bladder cancer will be diagnosed and about 12,500 people will die of the disease.
Anatomy of therapy
If the cancer is invasive, patients undergo a radical cystectomy, which includes removal of the entire bladder, nearby lymph nodes, part of the urethra (the tube through which urine leaves the body) and sometimes, parts of nearby organs to which the cancer may have spread. Patients treated with this procedure either must wear a bag outside the body to collect urine or have surgery to create internal pouches from intestinal tissue for urine collection.
Despite this aggressive therapy, patients with locally advanced bladder cancer have about a 50 percent chance that their disease will spread to distant sites in the body. The SWOG clinical trial was designed to test whether survival rates for those who undergo radical cystectomy could be improved by first treating patients with three cycles of a mixture of methotrexate, vinblastine, doxorubicin and cisplatin (a combination known as MVAC), drugs that might destroy microscopic traces of cancer that had migrated to bodily sites outside the bladder.
Among the 307 trial participants, half were randomly assigned to a group treated with radical cystectomy alone and half were assigned to a group treated with the drug regimen prior to surgery. Patients were followed for more than eight years after treatment. The median survival was 46 months for patients treated with surgery alone and 77 months for those treated with chemotherapy plus surgery. After five years, 57 percent of the patients in the combination-therapy group were alive compared to 43 percent for those treated only with surgery.
Of the patients who received combination therapy, 38 percent had muscle biopsies free of detectable disease at the time of surgery, compared to 15 percent of those who had surgery alone.
"The survival benefit of chemotherapy was strongly correlated with the absence of tumor pathology in the muscle," Tangen said. "Our next step, already underway in an ongoing SWOG study, is to examine other drug combinations that can cause this effect in an even greater percentage of patients while causing fewer side effects."