Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: Results of the randomised MRC ASTEC and NCIC CTG EN.5 trial

Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 3, 2007

Presenter: J. Orton
Presenter's Affiliation: Medical Research Council Clinical Trials Unit, London, UK
Type of Session: Scientific


  • Endometrial cancer is the most common gynecologic cancer among women in North America and affects over 40,000 women per year.
  • 75% of endometrial cancer cases present with disease confined to the uterus and surgery is the mainstay of therapy.
  • Patients with pathologic features that place them at a high risk for relapse generally receive adjuvant pelvic radiotherapy; however, there is limited data demonstrating an overall survival benefit to this treatment approach.
  • Adjuvant external beam radiotherapy may be over-treatment for FIGO stage I patients with endometrial cancer.

Materials and Methods

  • Patients who underwent surgery were then randomized to either external beam radiation therapy or no further treatment.
  • The median radiation dose delivered was 45 Gy in 1.8 Gy fractions.
  • Patients with stage IC/IIA disease or grade 3 disease were eligible for this trial.
  • Brachytherapy was allowed if it was used in both arms and decided upon before randomization.
  • Patients with positive para-aortic nodes were excluded although patients with positive pelvic nodes were considered eligible.
  • 452 patients were randomized to the EBRT arm and 453 were randomized to the surgery alone arm.
  • Patients and tumor related factors were well balanced between the two arms.
  • Median follow-up is 51 months.


  • Any grade 3 or 4 late toxicity was seen in 3% of the surgery alone arm and 7% of the radiation arm.
  • 5 year overall survival was the same in both arms at 84% (HR 1.02, p=NS)
  • Recurrence free survival was the same in both arms (HR 0.97, p=NS)
  • There was a significant decrease in isolated vaginal or pelvic recurrences in the EBRT arm (HR 0.53, p=0.038).
  • There was no evidence found that the effect of EBRT was more or less pronounced when looking at various subgroups as defined by: age, performance status, nodal involvement, depth of invasion, grade or extent of disease.
  • There was a trend towards improved survival with EBRT in centers that used brachytherapy with EBRT, but this was not statistically significant.

Author's Conclusions

  • There is no evidence that EBRT improves overall survival, disease free survival, or recurrence free survival.
  • 5 year overall survival was 84% in both arms.
  • 5 year disease free survival was 89% in both arms.
  • Toxicity was more commonly reported in the EBRT arm.
  • External beam radiotherapy alone is not indicated in the treatment of women with early stage endometrial cancer with an intermediate risk for relapse.
  • Further refinement of which subgroups of women might benefit from treatment would require an individual patient data meta-analysis of multiple trials.

Clinical/Scientific Implications

The authors of this trial attempted to sort out the role of adjuvant external beam radiotherapy for the treatment of early stage endometrial cancer with an intermediate risk of relapse. A critique of this study is that radiation was not standardized between centers. The suggestion that brachytherapy combined with external beam radiation may improve survival compared to surgery alone (although not statistically significant) is intriguing particularly since many American centers use vaginal brachytherapy +/- external beam radiation for these patients. In fact, many clinicians do not routinely use pelvic external beam radiation for any patients unless they have IC/IIA grade 3 disease. It is very difficult to sort out which particular subgroups of patients could benefit from pelvic radiation given the fact that differences in risks of relapse are fairly small between each subgroup of patients identified. The authors are correct to conclude that further refinement of which women may benefit from external beam therapy will require a meta-analysis because there just aren't enough patients in each particular subgroup of the trials that have been performed to give us the statistical power necessary to answer the question. Many of these patients may not need external radiation, and could do just fine with no further therapy or vaginal brachytherapy alone. However, more study is needed to define the selected subpopulations that may benefit from external beam therapy as it is clear treating the entire population of women is not of benefit. 

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