Vaginal Brachytherapy Linked to Improved Survival in Endometrial Cancer

Jonathan Strauss, MD

Vaginal brachytherapy (VB) has been linked to improved survival in women with stage I endometrioid adenocarcinoma of the uterus, according to a large database analysis published in Cancer.¹

“Using the [National Cancer Data Base (NCDB)], we found that vaginal brachytherapy after hysterectomy for stage I endometrial cancer was underused as compared to modern consensus guidelines,” Jonathan Strauss, MD, senior author of the study, said in an interview with OncLive. “We also found, that, after controlling for other factors, the use of vaginal brachytherapy was associated with a survival advantage. This suggests that greater adherence to current guidelines may improve patient outcomes.”

There has been a significant absence of survival benefit associated with reduction in locoregional recurrence (LRR) in this patient population. Prior to the current study, a wealth of data generally supported the role of pelvic RT after total abdominal hysterectomy bilateral salpingo oophorectomy in early-stage endometrial cancer. Reductions in cumulative incidence of LRR were seen across many of these studies, but these results did not translate into statistically significant advantages in overall survival (OS).

The current study hypothesized that the dearth of significantly advantageous OS results in this space may be attributed to limited sample sizes in the currently available randomized trials and their corresponding lack of statistical power.

Therefore, in this trial, the NCDB was used to evaluate the effect of postoperative RT on morbidity in a large population of women with stage IA or IB endometrioid adenocarcinoma of the endometrium.

A total of 44,309 patients were divided into 4 treatment groups: those who received no RT, those who received pelvis RT, those who received VB, and those who received both pelvis RT and VB.

Among 33,380 women with stage IA disease, 8.9% received adjuvant VB alone, 1.8% received adjuvant pelvic RT alone, and 0.9% received a combination of the 2 therapies. The remaining 88.4% of women with stage IA disease did not receive any form of adjuvant RT.

Among 10,929 women with stage IB disease, 27.7% received adjuvant VB, 13.1% received adjuvant pelvic RT, and 7.5% received a combination of pelvic RT and VB. Approximately 52% of women with stage IB disease did not receive any adjuvant RT.

A multivariate regression analysis assessed demographic and clinical predictors of treatment. For both women with stage IA and IB endometrial cancer, comorbid disease, living farther from the hospital, and lower grade histology were significantly associated with the omission of RT.

Among only women with stage IA disease, age <50 years and smaller tumor size were associated with the omission of RT. Receipt of care at a community hospital and age >70 years were associated with the omission of RT in women with stage IB disease.

These data on patient and tumor factors of prognostic significance are consistent with findings from smaller clinical cohorts.

Survival was compared among treatment groups with the log-rank test and Cox proportional hazards regression, which controlled for demographic and clinical covariates.

The Cox regression analysis indicated that older age, higher grade, larger tumor size, and comorbid disease were all significantly associated with poorer survival in both women with stage IA and IB disease.

For women with stage IA endometrial cancer, lower education level, Medicaid or uninsured status, and living farther from the hospital were associated with poorer survival.

In patients with stage IA disease, adjuvant VB was significantly associated with improved survival (HR, 0.81; 95% CI, 0.67-0.97; P = .021). In women with stage IB disease, adjuvant VB was also found to be significantly associated with improved survival (HR, 0.62; 95% CI, 0.51-0.74; P <.001).

These results are quite similar to data found in an earlier and much smaller analysis of the Surveillance, Epidemiology, and End Results Program database, which demonstrated a survival advantage associated with the use of postoperative RT in women with stage IB disease.

The recent national consensus guidelines from the American Society of Radiation Oncology and ASCO have attempted to optimize the selection of postoperative therapy by balancing the benefits seen with a reduction in LRR and the treatment-associated toxicities. For women with low-risk stage IA endometrial cancer, the guidelines currently support observation without RT. On the other hand, VB is recommended for women with higher-risk stage IA or any stage IB disease, and pelvic RT is recommended for women at highest risk (stage IB with high-grade histology).

Across both groups of women with stage IA and IB disease, 88% and 52%, respectively, did not receive RT. Moreover, an examination of a subset of women with stage IB grade 2 and grade 3/4 endometrial cancer—a group of patients that all guidelines say should receive RT—50% and 41%, respectively, received no RT. These results point to a clear disparity between what national guidelines recommend and what is actually happening in common clinical practice in the United States.

This disparity could potentially be explained by the excessive toxicities associated with RT, which some may feel outweigh the oncologic benefits. For example, in PORTEC-1, a study that evaluated long-term outcomes and quality of life of in patients with endometrial carcinoma, a questionnaire-based analysis of the treatment-associated toxicity showed that the receipt of pelvic RT was associated with increased rates of urinary incontinence, diarrhea, and fecal leakage, as well as reduced scores on an index of physical functioning.

In PORTEC-2, a trial in which VB was compared with pelvic RT in patients with endometrial cancer, multiple quality-of-life measures were superior in the VB arm. These results, along with the findings in the current study, suggest that VB is the preferred RT approach.

However, the results of the current study seem to support the notion that the discrepancy between the national guidelines and common clinical practice is actually attributed to the statistical power of the moderately sized randomized trials that may be insufficient to detect an OS benefit.

1. Rydzewski NR, Strohl AE, Donnelly ED, et al. Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: a National Cancer Data Base Study [published online August 10, 2016]. Cancer. doi:10.1002/cncr.30228.

Compared with patients who received no form of radiotherapy (RT), adjuvant VB was associated with a 19% and 38% reduction in the risk of death in women with stage IA and stage IB disease, respectively. It was also discovered that use of vaginal brachytherapy was not consistent with guideline recommendations.