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Women with stage I endometrial cancer do not need additional treatment with external beam radiation therapy. In fact, blended data from two trials suggest it may do more harm than good.
The two trials—A Study in the Treatment of Endometrial Cancer (ASTEC) from the United Kingdom and the National Cancer Institute of Canada Clinical Trials Group EN.5 trial—found external beam radiation therapy (EBRT) conferred no overall survival benefit after complete surgical removal of all visible tumor, and that the associated toxicity was more than twice as common, Dr. Ann Marie Swart said in a press briefing. Nor was EBRT of any benefit in reducing recurrence.
Consequently, "external beam radiation therapy is not routinely recommended," said Dr. Swart of the Medical Research Council Clinical Trials Unit, London, which funded ASTEC.
The results were hailed by Dr. Julie R. Gralow of the University of Washington, Seattle, who moderated the briefing. "This is very exciting news in the gynecologic oncology field. Almost 40,000 women in the United States alone are diagnosed with endometrial cancer and uterine cancer each year. About three-quarters of these women would qualify for this trial because their tumors are confined to the uterus. This is a lot of radiation we can avoid."
ASTEC and EN.5 started independently, but it was decided "very early on" to combine the analysis and monitoring, Dr. Swart said. Between October 1996 and April 2005, 905 women with stage I endometrial cancer were randomized to EBRT (452 patients receiving 40-46 Gy in 20-25 fractions to the pelvis) or to no further treatment (453 patients) until recurrence. Brachytherapy to the vagina was given to 52% of the patients in both arms.
At 51 months of follow-up, 5-year survival was 84%; 5-year disease-specific survival 89%; and 5-year recurrence-free survival 78% with no difference between arms. However, 56% (253) of patients given EBRT experienced toxicity vs. 24% (109) in the no-EBRT arm; rates of grade 3/4 toxicity were 7% (32) and 3% (15), respectively.
Dr. Swart noted the Post-Operative Radiation Therapy for Endometrial Carcinoma (PORTEC-1) trial, and Gynecologic Oncology Grop (GOG)-99 trial had similar findings. "Looking at the results in over 2,000 women from these trials, the hazard ratio is 1.02, which equals a 0.2% difference in overall survival in favor of EBRT. The good news from this trial is that women with early-stage endometrial cancer have quite good outcomes without EBRT, and these are women with a median age of about 65 years," she said.
Orton J. et al. Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: Results of the randomised MRC ASTEC and NCIC CTG EN.5 trial. Abstract 5504.
Commentary |
This study by Orton and colleaguesfocused on what role, if any, external beam radiation therapy (EBRT) has in patients with intermediate-risk endometrial carcinoma. This was defined as including patients having either FIGO stage IA or IB, endometrial carcinoma that was either grade 3 or papillary serous histology, and all patients with stage IC or IIA disease. Overall survival for this group of patients has been estimated to be 85%, and this study produced a very similar 5-year survival of 84%. When disease-specific survival was evaluated, again there was no significant difference with an overall 5-year disease-specific survival of 89%. The only significant difference favoring the use of EBRT was a decrease in the frequency of isolated vaginal or pelvic initial recurrences; that is, 4% with EBRT vs. 7% without (hazard ratio 0.53, P = .038). The study also showed no evidence that the effect of EBRT was smaller or greater in subgroups defined by age, performance status, nodal involvement, depth of invasion, grade, or extent of disease. The investigators presented a meta-analysis of the three major randomized trials that looked at the role of EBRT in intermediate-risk endometrial carcinoma: this study, GOG 99, and the PORTEC study. None found radiation had an impact on overall survival, but toxicity was substantially greater. These three trials make a convincing case that there is no role for EBRT in intermediate-risk endometrial carcinoma. — J. Tate Thigpen, M.D.
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