Brachytherapy Boosts Survival in Inoperable Endometrial Cancer

Kate Johnson

April 27, 2015

BARCELONA, Spain — Women with inoperable early-stage endometrial cancer survive longer if their treatment includes brachytherapy (BT) rather than external beam radiotherapy (EBRT) alone, according to a new analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database.

"Our results suggest that patients with medically inoperable stage I endometrial adenocarcinoma who are undergoing radiation should be treated with brachytherapy, if feasible," lead investigator Sahaja Acharya, MD, a resident physician in the Radiation Oncology Department of Washington University, in Saint Louis, Missouri, told Medscape Medical News.

The results were presented here at the European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum.

Although early-stage endometrial cancer is most commonly treated with total hysterectomy and bilateral salpingo-oophorectomy, about 10% of stage I disease is inoperable, either due to old age– related or obesity-related comorbidities, Dr Acharya explained.

Radiation is an alternative ― either external beam alone or brachytherapy, with or without EBRT ― but outcome data on these treatments are lacking, she said.

Better Outcomes Associated With Brachytherapy

The study included 460 patients from the SEER database who were diagnosed with stage I endometrioid adenocarcinoma and who underwent primary radiation between 1998 and 2011.

A total of 260 patients underwent EBRT alone; 200 received BT with or without EBRT. The percentage of patients undergoing BT ranged from 27% to 57% in any given year, with a slight downward trend during the study period, she noted.

After a mean follow-up of 35 months, the 3-year overall survival (OS) was 67% vs 40% favoring BT-treated patients (hazard ratio [HR], 0.67; P = .003).

Similarly, the 3-year cause-specific survival (CSS) was 82% vs 74% favoring BT-treated patients (HR, 0.61; P = .022).

There was a statistically significant difference in age between the two groups, with a median age of 76 years in the non-BT group and and 72 years in the BT group (P < .001). Because age and stage of disease are potentially confounding factors, the researchers performed an age- and stage-matched analysis in 304 patients.

This showed that the benefit of BT persisted for OS (HR, 0.62; P = .001) and CSS (HR, 0.57; P = .022).

"It is important to keep in mind that the improved outcomes are associated with brachytherapy, but no causal relationship can be made," said Dr Acharya.

It is possible that patients with more severe comorbidities were more likely to receive EBRT and that patients in the EBRT arm were treated with palliative rather than curative doses of radiation, but "the persistent difference in CSS suggests that BT may effect survival even for those deemed too sick to benefit from it," she commented.

However, "since the majority of BT patients also received EBRT, no conclusion can be made with regard to the impact of BT alone," she emphasized.

Adding Fuel to the Fire

"This study adds fuel to the argument that brachytherapy is paramount for inoperable endometrial cancer patients, where the potential for cure and risk of undertreatment are present," Sushil Beriwal, MD, associate professor of radiation oncology at the University of Pittsburgh School of Medicine, in Pennsylvania, told Medscape Medical News when approached for comment.

Dr Beriwal recently published a similar study using the National Cancer Data Base "in which we were able to account for different external beam radiation doses," he said. "Even when stratifying by external beam doses into palliative and more aggressive regimens, patients that received external beam radiation alone, without brachytherapy, had a higher risk of overall death on multivariable analysis," he said.

Dr Beriwal said that together, the two studies highlight two points: "the risks of abandoning brachytherapy and misjudging a patient's risk of death from other causes. In our study, we demonstrated that patients who received palliative external beam radiation had a higher risk of death, arguing that physicians are underestimating their risk of cancer-related death. Secondly, brachytherapy utilization appears low in a population that is potentially curable with this technique. Brachytherapy enables delivery of a high local dose to the uterine cavity, which is where endometrial cancer originates, illustrating its unique value in controlling disease. It is difficult to replicate this dose delivery through external beam radiation without putting nearby organs at risk."

Additionally, Dr Beriwal noted his group's recently published study of patients with stage I - II inoperable endometrial cancer who were treated with newer techniques of brachytherapy. "Specifically, patients were treated using image-guided brachytherapy, enlisting the aid of MRI. In that series, we showed high rates of disease control and very low rates of toxicity with this approach. Although the entire uterus was prescribed to receive a modest dose of radiation, the uterine cavity received almost three times as much, highlighting again the value of brachytherapy for this patient population."

Dr Acharya and Dr Beriwal have disclosed any no relevant financial relationships.

European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum: Abstract OC-0277. Presented April 26, 2015.


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