No Benefit With External-Beam Radiation for Endometrial Cancer

Allison Gandey

June 22, 2007

June 22, 2007 (Chicago) — A new trial is calling into question the decades-long tradition of combining radiation and surgery for patients with early endometrial cancer. Researchers here at the American Society of Clinical Oncology 43rd Annual Meeting report that adjuvant external beam radiation does not extend survival or reduce recurrence but does boost the risk for adverse effects.

"We've been able to look at that 30- or 40-year tradition to see whether it's supported by data, and we've shown that it is not supported by evidence," said senior investigator Peter Blake, MD, working on behalf of a group from the Medical Research Council Clinical Trials Unit, in London, United Kingdom, and the National Cancer Institute of Canada Clinical Trials Group, in Toronto, Ontario. "Physicians can now look at not offering adjuvant radiotherapy for intermediate-risk endometrial cancer patients who've had successful surgery," he noted during an interview.

Ann Marie Swart, MRCP, a senior clinical epidemiologist and 1 of the trial collaborators, presented the findings at a news conference. "Our study is the first to question the impact of radiotherapy on these women," Dr. Swart told Medscape. "The trend to withdraw conventional treatment has already started to happen, but I think now clinicians can be much more confident in doing so."

Colleague Jane Orton, MD, from the group gave the presentation for meeting attendees. The Adjuvant External Beam Radiotherapy in the Treatment of Endometrial Cancer (ASTEC) trial, combined with the Canadian study known as EN.5, represents the largest such analysis to date. The prospective, randomized trial enrolled 905 women with early-stage endometrial cancer. About half of patients received radiation while the rest did not.

Overall Survival and Recurrence Did Not Differ Significantly Between Groups

After a median follow-up of 51 months, overall survival and recurrence did not differ significantly between the 2 groups. Five-year overall survival was 84% in both groups. The proportion of women who were recurrence-free after 5 years was also similar, at 79% for women who received radiation vs 76% for those who did not.

"We were surprised at how well the patients as a whole did," Dr. Blake told Medscape. "When we designed this study in the mid-1990s, we were not expecting to see such high survival rates, and I think to some extent this is reflecting modern imaging techniques and much more accurate histological assessments," he said.

"This is exciting news out of the gynecological community," press briefing moderator Julie Gralow, MD, from the University of Washington, in Seattle, told reporters. "We can avoid giving patients radiation without any complications."

Discussing the findings at the meeting, Aaron Wolfson, MD, from the University of Miami, in Florida, presented several drawbacks to the study. He pointed out that 18% of patients in the external-beam-radiation group did not undergo protocol-specified therapy. He says that details of the treatment were not given with regard to field arrangements and beam energies — a fact that obscures complete evaluation of the toxicity data. And he noted that specific sites of failure in both study groups were not presented — especially concerning extrapelvic relapses.

"The Orton study also demonstrates that adjuvant external-beam-radiation therapy increases the risk of acute grade 1 and 2 adverse events but does not significantly increase early or late grade 3 or 4 toxicities," Dr. Wolfson added.

Acute and Late Toxicity

Adverse Events No External-Beam-Radiation Therapy (n=453), n (%) With External-Beam-Radiation Therapy (n=452), n (%)
Acute toxicity (post surgery and radiotherapy) 120 (26) 271 (60)
Worst score    
Mild 77 (17) 140 (31)
Moderate 38 (8) 111 (25)
Severe or life threatening 3 (<1) 19 (4)
Late toxicity grade 3/4 (3) (7)

Patient Outcomes After 51 Months of Follow-up

Outcome Total (n=905), n (%)
Alive 774 (86)
Dead 131 (14)
Cause of death  
From disease or treatment after recurrence 90
Other cause without recurrence 41

"The trial does not address what type of adjuvant therapy would be needed to improve overall survival in patients," Dr. Wolfson said at the meeting. "But it does suggest that external-beam-radiation therapy does not improve overall survival or disease-specific or recurrence-free survival." He says that further refinement of which subgroups of women might benefit from treatment would require an individual patient data meta-analysis.

"We've made tremendous progress in detecting and treating many cancers unique to women," Dr. Gralow told reporters. This study and others bring the field even closer to the goal of getting the best possible results with the fewest adverse effects, she said.

"We'll certainly have to rethink how we manage early-stage disease," Dr. Blake told Medscape. "The other thing we've shown in this study is that the great majority of patients who relapse have metastatic disease and do not relapse in the pelvis. Future treatments, I believe, will have to be systemic therapies used for patients identified most likely with more sophisticated algorithms than we've used in the past."

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 5504. Presented June 3, 2007.

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