Research indicates that women with locally advanced endometrial cancer are at high risk for both local and systemic recurrence. “Historically, these patients received external beam pelvic radiotherapy, which decreased the risk of pelvic relapse,” says Daniela Matei, MD. “In recent years, it became clear that addition of systemic chemotherapy to radiotherapy reduces the rate of distant metastasis and should be incorporated in the treatment schema. Systemic chemotherapy had been compared to radiotherapy in a previous randomized trial for women with locally advanced uterine cancer and was found to lead to better overall survival and progression free survival. While adding the two modalities of treatment seemed like the rational solution to achieve optimal outcomes, only a randomized clinical trial could help definitively answer this question.”
For a study published in the New England Journal of Medicine, Dr. Matei and colleagues tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival than six cycles of combination chemotherapy alone in patients with stage III-IVA endometrial carcinoma. Secondary endpoints were overall survival, acute and chronic toxicities, and quality of life.
“At 60 months, 59% and 58% of patients were alive, recurrence free on the combined regimen and chemotherapy alone arms, respectively,” explains Dr. Matei. “Addition of radiation to chemotherapy caused a significant decrease in the incidence of vaginal recurrence and pelvic or para-aortic node recurrences, thus providing better local control of the disease. Despite this, the overall risk of relapse was similar between the groups, because the risk for distant recurrence was higher in the combined therapy arm. Exploratory analyses did not identify any subgroup of patients who may have benefited from the combined approach compared with chemotherapy alone. Additionally, constitutional, gastrointestinal, renal/genitourinary, and musculoskeletal adverse events were more frequent in patients receiving the combined therapy. Indices of quality of life were measured and found to be slightly lower in this group as well.”
Dr. Matei notes that future research in this area should assess the addition to chemotherapy of biological agents that inhibit key pathways driving disease progression. In the meantime, she says the findings support that treatment of women with locally advanced endometrial cancer focus on chemotherapy completion.
Rebecca Shover