Two common adjuvant treatments for women with early endometrial cancer—removing the pelvic lymph nodes or external beam radiotherapy (EBR)—should not be part of routine care, according to two articles published online before print Dec. 13 in The Lancet.
The articles were written by Ann Marie Swart, MD, Medical Research Council Clinical Trials Unit in London and Professor Henry Kitchener, University of Manchester in the United Kingdom (U.K.), and colleagues on behalf of the ASTEC study group and the ASTEC/EN.5 writing committee.
The first article examined the benefits of removal of the pelvic lymph nodes (pelvic lymphadenectomy), in addition to the standard treatments of hysterectomy and removal of both ovaries and both fallopian tubes (bilateral salpingo-oophorectomy/BSO).
Removal of the pelvic lymph nodes has been used to establish whether or not there is disease outside the uterus and is also a therapeutic procedure. In the randomized trial, the researchers analyzed 1,408 women from 85 centers in the U.K., Poland, South Africa and New Zealand with endometrial cancer believed to be localized.
Of these, 704 were randomly assigned to standard surgery (hysterectomy and BSO, peritoneal washing, and palpation of para-aortic nodes; while the other 704 were assigned to standard surgery plus pelvic lymphadenectomy. The primary outcome was survival.
The researchers found that, after a median follow-up of approximately three years, 88 women in the standard surgery died compared with 103 in the lymphadenectomy group. When looking at the combined chances of death or recurrent disease, 144 women in the lymphadenectomy group experienced one or the other, compared with 107 in the standard group — an increased risk of 35 percent for women having their pelvic lymph nodes removed, according to the results.
The authors concluded that the results showed shown no evidence of a benefit for systematic lymphadenectomy for endometrial cancer in terms of overall, disease-specific, and recurrence-free survival.
In the second article, the effects of EBR were examined. EBR was offered to women who have had successful surgery (hysterectomy/BSO) for early endometrial cancer, but are considered to have an increased risk of recurrence due to their particular cancer pathology. The authors analyzed 789 women from the ASTEC study plus a further 116 from the EN.5 study, from 112 centers in the U.K., Canada, Poland, Norway, New Zealand, Australia and the United States.
The patients were randomly assigned after surgery to observation (453 women) or to EBR (452). EBR was delivered in 20 to 25 daily fractions up to the target dose. The primary outcome was survival.
The researchers found that, after a median follow-up of 58 months, 68 women in the observation group died, compared with 67 in the EBR group. There was no evidence that overall survival was higher in the EBR group, and five-year overall survival was 84 percent in both groups. When combined in a meta-analysis with other trials, the results showed no benefit for overall survival for EBR. With brachytherapy (placement of a small radioactive pellet near to the cancer site) used in 53 percent of women in the trial, the local recurrence rate in the observation group at five years was 6 percent.
According to the authors, the ASTEC/EN.5 trial has shown no evidence of a benefit for external beam radiotherapy for early endometrial cancer at intermediate or high risk of recurrence, in terms of overall, disease-specific, and disease-specific recurrence-free survival.
“Combining these findings with data from other trials, we can exclude even a very small benefit of radiotherapy on overall survival. Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment to improve survival for women with early endometrial cancer at intermediate or high risk of recurrence, and brachytherapy might be preferred for local control,” they noted.