Brachytherapy Yields Better Survival in Endometrial Cancer

From Medscape Education Clinical Briefs
Brachytherapy Yields Better Survival in Endometrial Cancer CME/CE

News Author: Kate Johnson
CME Author: Charles P. Vega, MD



Endometrial cancer is associated with high rates of morbidity and mortality, and women with stage III or IV cancer, in which the tumor has extended outside of the uterus, are at particularly high risk for worse outcomes. These cases often involve multiple modalities to treat the cancer. A previous systematic review by Galaal and colleagues, which was published in the May 2014 issue of the Cochrane Database of Systematic Reviews, evaluated the efficacy of adjuvant chemotherapy among women with stage III or IV endometrial carcinoma.

The review focused on 4 randomized trials, which involved a total of 1269 women. Adjuvant chemotherapy was associated with significantly better results for overall survival and progression-free survival compared with adjuvant radiotherapy, regardless of stage III or IV cancer status. This benefit came at the price of higher rates of hematologic and neurologic adverse effects, and a fivefold increase in the rate of treatment discontinuation in comparing chemotherapy with radiotherapy. Limited data suggested that treatment with cisplatin/doxorubicin/paclitaxel yielded similar rates of progression-free survival as cisplatin/doxorubicin treatment, with more adverse effects associated with triple therapy.

Stage I endometrial cancer is usually treated with surgery, but can other treatments be effective for women who cannot undergo surgery because of medical reasons? The current study by Acharya and colleagues evaluates this issue.
Study Synopsis and Perspective

Women with inoperable early-stage endometrial cancer survive longer if their treatment includes brachytherapy rather than external beam radiotherapy 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, approximately 10% of stage I disease is inoperable, either because of comorbidities related to advanced age or those related to obesity, Dr Acharya explained.

Radiation is an alternative -- either external beam alone or brachytherapy (with or without external beam radiotherapy) -- 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 external beam radiotherapy alone; 200 received brachytherapy with or without external beam radiotherapy. The percentage of patients undergoing brachytherapy 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 rate was 67% vs 40% favoring brachytherapy-treated patients (hazard ratio [HR], 0.67; P = .003).

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

There was a statistically significant difference in age between the groups, with a median age of 76 years in the nonbrachytherapy group and 72 years in the brachytherapy group (P < .001). Because age and stage of disease are potentially confounding factors, the researchers performed an age-matched and stage-matched analysis in 304 patients. This showed that the benefit of brachytherapy persisted for overall survival (HR, 0.62; P = .001) and cause-specific survival (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 external beam radiotherapy and that patients in the external beam radiotherapy arm were treated with palliative rather than curative doses of radiation, but "the persistent difference in CSS [cause-specific survival] suggests that BT [brachytherapy] 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 [external beam radiotherapy], 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 2 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 to 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 [magnetic resonance imaging]. 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 no relevant financial relationships.

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