Pelvic Radiation Therapy Preferred Over Brachytherapy Plus Chemotherapy in Treatment of High-Risk Endometrial Cancer


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Marcus Randall, MD

Marcus Randall, MD

VAGINAL CUFF BRACHYTHERAPY plus chemotherapy failed to show superiority over pelvic radiation therapy for women with high-risk stage I–II endometrial cancer in a phase III trial.1 Furthermore, vaginal cuff brachytherapy plus chemotherapy led to more pelvic and para-aortic nodal recurrences and more frequent acute toxicity compared with pelvic radiation therapy. These findings, which support pelvic radiation therapy as the preferable option in this setting, were presented at the 2017 American Society for Radiation Oncology (ASTRO) Annual Meeting. 

“This large randomized phase III study did not demonstrate the superiority of vaginal cuff brachytherapy and chemotherapy over pelvic external radiation therapy. Relapse-free survival and overall survival are not improved by vaginal cuff brachytherapy. This conclusion applies to all subgroups analyzed, including patients with serous and clear cell histology. Pelvic radiation therapy remains an appropriate—and probably preferable—treatment for high-risk, early-stage, endometrial carcinoma,” said lead author Marcus Randall, MD, Markey Foundation Endowed Chair and Professor, Department of Radiation Medicine, University of Kentucky Health Care, Lexington. 

“Better treatment strategies to address the risk of systemic disease will be necessary to improve outcomes,” Dr. Randall added. 

RADIATION THERAPY AFTER CHEMOTHERAPY IN ENDOMETRIAL CANCER

  • In patients with high-risk, early-stage endometrial cancer, pelvic radiation therapy is preferred to brachytherapy/chemotherapy, according to the results of a randomized phase III trial.
  • Relapse-free survival was identical for these strategies.
  • Brachytherapy/chemotherapy led to more vaginal and para-aortic nodal failures and had greater acute toxicity.
  • The frequency of long-term toxicity was similar in the two arms.
  • Better approaches are needed to reduce recurrence, but for now, pelvic radiation therapy is the preferred choice, taking into consideration cost, side effects, and the complexity of the procedure.

Management of high-risk endometrial cancer is controversial, he explained. Most recurrences occur at the vaginal cuff, although metastatic disease occurs in one of five high-risk patients, he added. In recent years, there has been a trend toward an increased use of vaginal brachytherapy to address the risk of recurrence in the vaginal cuff. “Vaginal brachytherapy in high-risk patients is more experimental but nevertheless is becoming more commonly used,” Dr. Randall revealed. 

Study Details 

NRG ONCOLOGY investigators conducted the phase III randomized, multicenter GOG-249 trial to determine whether adjuvant brachytherapy/chemotherapy was superior to adjuvant pelvic external radiotherapy. The primary outcome measure was relapse-free survival; secondary endpoints were overall survival, patterns of failure, and toxicity/functioning. 

The study enrolled 601 patients randomized to receive either brachytherapy plus chemotherapy (paclitaxel/carboplatin for 3 cycles) or pelvic external radiation (64% were treated with conformal radiation and 36%, intensity-modulated radiation therapy). “This was the first Gynecologic Oncology Group trial to allow intensity-modulated radiation therapy,” Dr. Randall noted. 

Seventy-five percent of patients had stage I disease, and 25% had stage II disease. The median age was 62 years. Both groups had a similar mix of histology (about 15% serous and about 5% clear cell). Lymph node dissection was not required but was performed in 89% of patients. Median follow-up was 53 months. 

Key Findings 

PATIENT ACCRUAL was from March 2009 to February 2013. Of the 601 patients enrolled, 527 were treated with follow-up available (259 in the pelvic radiotherapy group and 268 in the brachytherapy/chemotherapy group). Completion rates for prescribed therapy were 91% for pelvic radiotherapy and 87% for brachytherapy/chemotherapy. The 36-month relapse-free survival rate was identical in the two arms: 82%. 

Median overall survival at 3 years was 91% for pelvic external radiation and 88% for brachytherapy/chemotherapy, representing a nonsignificant numeric trend. Outcomes were similar for both strategies in all prespecified subgroups. 

Pelvic and para-aortic nodal failures were more common in the brachytherapy/chemotherapy arm at 5 years: 9.2% vs 4.4%, respectively. No difference between the groups was observed for the rate of vaginal recurrence and distant recurrence: 2.5% and 18%, respectively, in both arms. 

“Pelvic radiation therapy remains an appropriate—and probably preferable—treatment for high-risk, early-stage, endometrial carcinoma.”
— Marcus Randall, MD

Brachytherapy/chemotherapy increased the rate of acute toxicity. Grade 3 or higher acute toxicity occurred in 187 patients compared with 32 patients treated with pelvic external radiotherapy. The rate of late grade 3 or higher toxicity was similar in the two arms: 37 patients and 35 patients, respectively. 

“Researchers can now focus on determining the optimal radiation dosing and fractionation schedules for various patient subgroups, as well as refining the techniques we use to deliver external-beam therapy to the pelvis and to continue to investigate therapies to decrease distant failures in this high-risk group,” Dr. Randall proposed. 

‘Value’ of Therapy 

Paul Harari, MD

Paul Harari, MD

COMMENTING ON THIS STUDY, ASTRO President Paul Harari, MD, said. “We want to serve our patients with the highest-quality cancer treatment and remain conscious of the side-effect profile and cost value. This study demonstrates the value of pelvic radiation to exert effective local tumor control in patients with high-risk endometrial cancer. These data encourage practitioners who may have adopted approaches that utilize more lengthy, complex, and costly regimens to at least consider that this simple regimen of pelvic irradiation may in fact be the most cost-effective and valuable for patients.” 

Dr. Harari, who moderated the press conference where these findings were discussed, is the Jack Fowler Professor and Chairman of the Department of Human Oncology at the University of Wisconsin School of Medicine and Public Health, Madison. ■

DISCLOSURE: Drs. Randall and Harari reported no conflicts of interest. 

REFERENCE 

1. Randall M, Filiaci V, McMeekin D, et al: A phase III trial of pelvic radiation therapy versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy in patients with high-risk, early stage endometrial cancer: A Gynecology Oncology Group study. 2017 ASTRO Annual Meeting. Abstract LBA1. Presented September 25, 2017. 


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