Pooled results: external beam radiotherapy no benefit to OS in endometrial cancer

Adjuvant external beam radiotherapy should not be part of routine treatment for women with intermediate- or high-risk early-stage disease.

External beam radiotherapy showed no benefit to OS, disease-specific survival and disease-specific recurrence-free survival in early endometrial cancer at intermediate or high risk of recurrence, according to a meta-analysis based on pooled results of the ASTEC and EN.5 trials.

Researchers analyzed the results of both trials, which randomly assigned women with early-stage endometrial cancer and pathological features suggesting intermediate or high risk of recurrence and death to external beam radiotherapy or observation after surgery.

The pooled results included 905 women from 112 centers in seven countries. Four-hundred fifty-three patients were randomly assigned to observation and 452 to external beam radiotherapy. The target dose of radiotherapy was 40 to 46 Gy in 20 to 25 daily fractions to the pelvis; patients received treatment five times per week. Baseline data for both arms were mostly balanced, though a higher percentage of high-risk women were included in the observation arm compared with the radiotherapy arm (25% vs. 20%).

Toxicity and mortality

The percentage of women who experienced acute toxicity was higher in the external beam radiotherapy arm compared with observation (57% vs. 27%). Similarly, severe or life-threatening toxicity occurred in three women from the observation arm vs. 14 women from the radiotherapy arm. Late toxicity, which consisted mostly of gastrointestinal or urogenital toxicities, were more common in the radiotherapy arm compared with observation (61% vs. 45%). Severe late toxicity occurred in 15 women from the observation arm vs. 30 from the radiotherapy arm. Life-threatening toxicity occurred in four women, all of whom received radiotherapy.

Median follow-up was 58 months at which time 135 patients had died; 68 from the observation arm and 67 from the radiotherapy arm. According to the researchers, the OS curves provided no evidence of a difference between the two arms; the HR was 1.05 (95% CI, 0.75-1.48). Five-year OS was 84%.

Twenty-six deaths unrelated to disease or treatment occurred in the observation arm and 22 occurred in the radiotherapy arm; however, 42 patients from the observation arm and 45 from the radiotherapy arm died from disease or treatment. Using the non-disease and treatment-related deaths as a competing risk, an analysis yielded a HR of 1.13 (95% CI, 0.74-1.72). Five-year disease-specific survival was 90% in the observation arm and 89% in the radiotherapy arm.

No benefits from external beam radiotherapy

According to the researchers, tests for interaction for OS (P=.83) and disease-specific survival (P=.45) suggested that external beam radiotherapy provided no different effects based on intermediate- or high-risk subgroups. Similarly, tests for interaction for OS (P= 0.79) and disease-specific survival (P=.22) did not suggest a different effect of external beam radiotherapy on women who had lymphadenectomy as part of primary surgery.

“Combining these findings with data from other trials, we can exclude even a very small benefit of radiotherapy on OS,” the researchers wrote.

They updated a meta-analysis of pooled data, including the ASTEC and EN.5 results, and found that the effect of external beam radiotherapy on OS yielded an HR of 1.04 (95% CI, 0.84-1.29). The results ruled out an absolute benefit of more than a 3% increase in OS from adjuvant pelvic radiotherapy, according to the researchers.

In an accompanying editorial, Michael Höckel, MD, and Nadja Dornhöfer, MD, department of obstetrics and gynecology at the Women’s and Children’s Center at the University of Leipzig in Germany, addressed the future of endometrial carcinoma treatment.

“Appropriate studies need to explore whether locoregional tumor control can be improved and distant metastases prevented by better surgery and different systemic therapies.”