Brachytherapy-chemotherapy combination not superior to radiation alone for recurrence-free and overall survival; radiation alone demonstrated better pelvic control, fewer severe side effects.

In a new phase 3 trial report from the National Clinical Trial Network group, NRG Oncology, recurrence-free and overall survival rates for women with stage I-II high-risk endometrial cancer were not superior following vaginal cuff brachytherapy plus chemotherapy when compared with pelvic radiation therapy. Risks of pelvic and para-aortic nodal recurrence and frequency of short-term side effects were greater for the brachytherapy-chemotherapy approach. High completion rates for each treatment arm suggest that both therapies are well-tolerated by patients.

Findings were presented at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Clinical trials in the early 2000s (e.g., Gynecology Oncology Group (GOG)-99, PORTEC) found that external beam radiation therapy to the pelvis following surgery to remove early-stage endometrial cancer reduced tumor recurrence rates compared with post-surgical observation alone, which established adjuvant pelvic radiation as the standard treatment for stage I-II patients. In recent years, however, many physicians have begun treating early-stage patients at higher risk of recurrence with an alternative approach of vaginal cuff brachytherapy followed by chemotherapy. GOG-249 was designed to directly compare the two approaches.

“Our trial clearly demonstrates that adjuvant pelvic radiation should remain the standard of care for high-risk, early-stage endometrial cancer patients. It also suggests that the trend in our field of abandoning pelvic radiation in favor of chemotherapy-brachytherapy combinations for high-risk patients is premature and not supported by clinical evidence,” said Marcus Randall, MD, FASTRO, lead author of the study and a professor of radiation medicine at the University of Kentucky in Lexington. “The cohort of women with high-risk histologies did not demonstrate any benefit from the addition of chemotherapy, but they did experience worse nodal control rates and more short-term side effects.”

GOG-249 was a phase 3 randomized trial designed to test whether adjuvant brachytherapy plus chemotherapy improved recurrence-free survival compared with the standard treatment of pelvic radiation for early-stage, high-risk endometrial cancer. Eligible patients included women with high-risk stage I-II histology, including stage II tumors, stage I-II serous or clear-cell carcinomas and stage I endometrioid tumors if the patient demonstrated clinic-pathologic features associated with a high risk of recurrence, based on criteria established in the GOG-33 trial and used in the GOG-99 trial.

Most patients (74%) had stage I disease and endometrioid histology (71% vs 15% serous and 5% clear-cell carcinomas). The median patient age was 63 years. All patients underwent hysterectomy prior to radiation or chemoradiation therapy.

One of two treatment arms was randomly assigned to patients: adjuvant external beam RT to the pelvis (PXRT) or vaginal cuff brachytherapy plus chemotherapy (VCB/C). The PXRT group (n=301) received a median radiation dose of 45 Gray (Gy) delivered over five weeks through standard four-field radiation or intensity-modulated radiation therapy (IMRT). Patients with serous, clear-cell or stage II tumors were eligible for a vaginal cuff brachytherapy boost, and 35% of the cohort received this additional therapy. The VCB/C group (n=300) received either high-dose rate (HDR) or low-dose rate (LDR) brachytherapy followed by three cycles of chemotherapy including paclitaxel (175 mg/m 2–3 hour) and carboplatin (AUC 6–21 days). Nearly all 601 patients accrued for the trial completed treatment (91% PXRT, 87% VCB/C).

There were no statistically significant increases in recurrence-free survival (RFS) or overall survival (OS)