Elsevier

Gynecologic Oncology

Volume 92, Issue 3, March 2004, Pages 744-751
Gynecologic Oncology

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study

https://doi.org/10.1016/j.ygyno.2003.11.048Get rights and content

Abstract

Background. Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease).

Methods. Four hundred forty-eight consenting patients with “intermediate risk” endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup.

Results. Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P = 0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH = 0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P = 0.557).

Conclusions. Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.

Introduction

Every year more than 36,000 women are diagnosed with adenocarcinoma of the endometrium [1]. Historically, many of these women have received postoperative radiation based on the belief that this treatment would decrease relapses [2], [3], [4], [5]. Data supporting this routine treatment are largely from single-institution retrospective reports [6], [7]. There seems to be increasing agreement that women presenting with noninvasive endometrial adenocarcinoma are at such a low risk of recurrent disease that radiation therapy (RT) should not be included in their treatment plan. The use of radiation therapy for International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult) remains controversial in endometrial adenocarcinoma [10], [11]. Creutzberg et al. [8] examined this question in a prospective randomized study. Their data suggested that postoperative radiation therapy reduces locoregional recurrence in stage I endometrial carcinoma but is not indicated in women under 60 years and those with grade 2, superficially invasive tumors. Analysis of their study is limited as complete surgical staging was not an entry requirement and the actual number of women with FIGO stage I endometrial adenocarcinoma remains unclear. To address the utility of postoperative radiation therapy in women with stage IB, IC, and II (occult) endometrial cancer, the Gynecologic Oncology Group (GOG) initiated this study.

Section snippets

Materials and methods

For this study, intermediate risk endometrial adenocarcinoma was defined based on data from a surgical staging protocol (GOG # 33) [9]. These data suggested that all women found to have any degree of myometrial invasion with adenocarcinoma of any grade and no evidence of lymph node involvement (International Federation of Gynaecology and Obstetrics [FIGO] stage IB, IC, IIA (occult), and IIB [occult]) should be considered as a member of the intermediate risk group, expected to have a 5-year

Results

Between June 1987 and July 1995, 448 women were entered into this study. After central evaluation, 392 women (88%) were determined to be eligible. Of the 56 women found to be ineligible (25 assigned to NAT and 31 assigned to RT), the GOG Gynecologic Oncology Committee determined that 38 women (8.5%) had incomplete staging; the majority had unilateral, instead of the required bilateral lymph node sampling. The remaining 18 women (4%) were found to have an ineligible histology or FIGO stage. All

Discussion

The role of adjuvant postoperative irradiation has been studied previously in two large randomized trials, neither of which required detailed surgical staging evaluation. A Norwegian from the 1970s followed 540 stage I endometrial cancer patients who were randomly assigned to receive either vaginal irradiation alone (control group) or vaginal plus external pelvic radiation therapy [23]. The latter group had fewer vaginal and pelvic recurrences (1.9 versus 6.9% P < 0.01) than the control group,

Acknowledgements

Supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). The following Gynecologic Oncology Group institutions participated in this study. University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, University of Minnesota Medical

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