The standard of care for women with stage III/IVA endometrial cancer following surgery has been chemotherapy and radiation to prevent recurrence. But in a surprising new finding, radiation combined with chemotherapy did not increase recurrence-free survival in these women, reports a National Cancer Institute-sponsored Gynecology Oncology Group study led by a Northwestern Medicine scientist/physician.
This is the first study comparing the combined regimen to chemotherapy alone. It will be published June 12 in the New England Journal of Medicine.
"The trial was supposed to be a positive trial demonstrating that the combined regimen was superior to chemotherapy given alone," said lead investigator Dr. Daniela Matei, a professor of medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine gynecological oncologist. "Our results indicate the combined regimen of radiation and chemotherapy did not result in an improvement in recurrence-free survival, and that chemotherapy alone remains the standard of care for stage III uterine cancer."
Matei also is the co-leader of the Translational Research in Solid Tumors Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Endometrial cancer, which begins in the uterus, is the most common gynecologic cancer with most cases occurring in women after age 55. About 62,000 new cases will be diagnosed this year. Occurrence of and mortality from endometrial cancer is rising, which may be tied to the obesity epidemic, Matei said.
Usually endometrial cancer presents with post-menopausal irregular bleeding. There is no screening, but any bleeding after menopause should trigger a doctor's visit and examination, Matei said. Most cases are diagnosed at an early stage and are cured with surgery alone.
The phase 3 trial randomly assigned 736 eligible patients to one of two possible treatment arms. A group of 346 received a combined treatment consisting of chemotherapy and radiation over 21 weeks, a second group of 361 women received chemotherapy alone over 17 weeks.
A median follow-up of six months after the randomized phase 3 trial showed the recurrence-free survival for the two arms of the trial were very similar: 59 percent for the group that got chemotherapy and radiation and 58 percent for chemotherapy alone.
Patients who received both chemo and radiotherapy had fewer recurrences in the pelvis, however this did not translate into improved recurrence-free survival, because there were relapses outside of the radiation field.
"For patients at high risk of a local relapse, radiation may be occasionally necessary to prevent pelvic recurrences," Matei said.
Radiation can cause immediate as well as chronic side effects that impact the quality of life of treated patients. These include diarrhea, low blood counts, urinary symptoms and others.
"An important consideration is the fact that concomitant delivery of chemo and radiotherapy can result in decreased tolerance of the treatment and incomplete delivery of chemotherapy," Matei said. "More than 25 percent of patients assigned to the combined arm were not able to complete chemotherapy on this study."
Radiation was historically used first, before it was recognized that chemotherapy has a role in the treatment of endometrial cancer. After chemotherapy was added to the treatment, radiation continued to be used as a standard approach.
Journal information: New England Journal of Medicine
Provided by Northwestern University