FIGO stage IIIC endometrial carcinoma: Prognostic factors and outcomes

Abstract

Objectives

Investigate the clinicopathologic characteristics, nodal distribution, and postoperative treatment of patients with FIGO stage IIIC endometrial carcinoma and determine patterns of recurrence and survival.

Methods

A retrospective review of 85 patients who underwent surgical staging with lymph node dissection at a single institution between 1979 and 2005 was performed. Data collected from patient charts included demographics, treatment, recurrence and survival. Variables were compared using the log-rank and X2 tests, and multivariate analysis was performed.

Results

Of 1487 patients who underwent surgical staging for endometrial cancer, 104 (7.0%) were diagnosed with stage IIIC disease and 85 of these were analyzed. Stage was determined by positive pelvic lymph nodes (PLN) in 54 patients, and positive para-aortic lymph nodes (PaLN) ± PLN in 31 patients. With a median follow up of 50 months, 5-year overall survival (OS) was 61.3%, recurrence-free survival (RFS) was 58.0%, and disease-specific survival (DSS) was 71.9%. Median OS, RFS and DSS were 131 months, 131 months, and not attained, respectively. Five-year OS and RFS with positive PaLN were 48.8% and 44.4% respectively, compared to 69.7% and 65.6% with positive PLN only. On multivariate analysis, age, non-endometrioid histology, and > 50% invasion were significantly associated with OS; age and non-endometrioid histology were associated with RFS. Disease recurred in 21 patients (24.7%): 15 distant, 4 abdominal, 1 para-aortic, and 1 pelvic. Disease recurred outside the field of radiation in all patients.

Conclusions

Endometrial cancer patients with FIGO stage IIIC had a 5-year OS of 61.3%, a RFS of 58.0% and a DSS of 71.9% in this series. Because of the high proportion of distant sites of recurrence (71.4%), recurrence outside the radiation field (100%), and mortality after recurrence (86.3%), multimodality therapy should be considered.

Introduction

Endometrial carcinoma is the most common gynecologic malignancy in the United States, with an estimated 40,100 new cases diagnosed in 2008. Most patients are diagnosed with early-stage disease, which is cured in the majority of patients with surgery alone [1]. The presence of extrauterine disease significantly affects recurrence rates and survival, which emphasizes the importance of identification of sites of disease spread and provision of appropriate adjuvant postoperative therapy [2], [3], [4], [5], [6].

In 1987, the Gynecologic Oncology Group (GOG) published results of Protocol 33, which investigated the usefulness of surgical staging in patients with endometrial cancer clinically confined to the uterus. They found that 22% of the 621 patients had extrauterine disease, including disease spread to the pelvic lymph nodes in 9% and to the para-aortic lymph nodes in 5%. In response to this report and others, the International Federation of Gynecology and Obstetrics (FIGO) changed to a surgical staging system in 1988 [7]. The performance of pelvic and para-aortic lymphadenectomy as part of surgical staging of endometrial cancer has increased due to reports showing both diagnostic and therapeutic advantages [3], [8], [9], [10]. In patients with stage IIIC disease, resection of para-aortic lymph nodes in particular has been shown to give a therapeutic advantage [11], [12], [13], [14], [15], [16].

The mainstay of adjuvant treatment for advanced endometrial cancer has been radiation. Small et al. and others showed tolerable toxicity and good pelvic and abdominal locoregional control with whole abdomen radiation. More recently, adjuvant treatment for patients with advanced disease has included both radiation and chemotherapy. In GOG 122, patients with advanced endometrial cancer treated with chemotherapy (cisplatin and doxorubicin) had an improved OS and PFS compared to those undergoing whole abdomen irradiation [17].

The objectives of this study are to analyze the overall survival (OS), recurrence-free survival (RFS) and disease-specific survival (DSS) of a large series of patients with stage IIIC endometrial cancer at a single institution where lymphadenectomy was performed for almost all patients with endometrial cancer since 1979, to describe prognostic differences based on location of lymph node metastases, and to analyze patterns of recurrence in relationship to treatment provided.