Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases

doi:10.1016/j.ygyno.2013.10.029

Gynecologic Oncology

Volume 132, Issue 1, January 2014, Pages 70-75

https://doi.org/10.1016/j.ygyno.2013.10.029 Get rights and content

Highlights

•
Stage, expression of estrogen/progesterone receptor (ER/PR) and nodal metastasis are significantly associated with overall survival in the univariate analysis.
•
Bilateral salpingo-oophorectomy (BSO) is an independent predictor for recurrence free survival but not overall survival.
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Analysis of 33 patients with recurrence, ER/PR and cytoreductive resection of recurred lesions is independent predictors for survival after recurrence.

Abstract

Objective

To assess prognostic factors associated with disease-related survival in endometrial stromal sarcoma (ESS) using the 2009 FIGO staging system.

Methods

From January 1990 to January 2012, 114 patients with ESS were identified at the Samsung and Asan Medical Center and data were retrospectively analyzed.

Results

Ten (8.7%) patients died of the disease and 33 (28.9%) patients relapsed. The 5- and 10-year overall survival (OS) rates for the entire cohort were 92.6% and 87.1%, respectively, and the 5- and 10-year recurrence-free survival (RFS) rates were 71.8% and 52.1%, respectively. The estimated median survival after recurrence for the 33 patients whose tumors relapsed was 133 months (95% CI, 7.7–258.4), and 5-year survival after recurrence was 68.9%. Stage I (P = 0.006), estrogen and/or progesterone receptor (ER/PR) positivity (P = 0.0027), and no nodal metastasis (P = 0.033) were associated with a good prognosis for OS in the univariate analysis. Ovarian preservation was revealed to be an independent predictor for poorer RFS (HR, 6.5; 95% CI, 1.23–34.19; P = 0.027). Positivity for ER/PR (HR, 0.05; 95% CI, 0.006–0.4; P = 0.006) and cytoreductive resection of recurrent lesions (HR, 0.14; 95% CI, 0.02–0.93; P = 0.042) were independent predictors of better survival after recurrence.

Conclusions

Stage, expression of ER/PR, and nodal metastasis are significantly associated with OS in ESS. Bilateral salpingo-oophorectomy (BSO) as the primary treatment and cytoreductive resection of recurrent lesions should be considered for improving survival of patients with ESS.

Introduction

Endometrial stromal sarcomas are rare, pure mesenchymal tumors, comprising about 0.2% of all uterine malignancies and 10–25% of all uterine sarcomas [1]. Endometrial stromal sarcomas were formerly divided into low-grade and high-grade tumors with the degree of differentiation determined by a threshold of 10 mitoses per 10 HPF [2]. However, high-grade tumors have distinct histology and clinical properties compared with low-grade tumors. Currently, the term endometrial stromal sarcoma (ESS) refers only to low-grade ESS according to the 2003 World Health Organization (WHO) classification.

ESSs are generally characterized by indolent behavior and a favorable prognosis. The 5-year overall survival (OS) rates of ESS patients is reported to be 80–100% [3]. In addition, in most patients, the disease is diagnosed at an early stage; 65–86% of ESSs were confined to the uterus at diagnosis [4], [5], [6]. However, late recurrence is common even in patients with early stage disease, with more than one-third of patients developing recurrent disease [3], [5], [6]. Surgery including total abdominal hysterectomy and bilateral salpingo-oophorectomy (BSO) is considered the standard initial therapy [1], [4], [7]. However, the merits of BSO in young premenopausal patients remain controversial. The role of lymphadenectomy and the prognostic significance of lymph node metastasis have not been clearly defined [3], [8], [9]. In adjuvant treatment, radiotherapy, chemotherapy, and hormonal therapy are the current options. However, the optimal adjuvant treatment remains unclear [7].

Due to the rarity of these tumors and the heterogeneity including high-grade tumors or various histologic subtypes of uterine sarcoma of published studies, existing data for ESS are limited to evaluations of the natural history and optimal management of ESS. Furthermore, there is no obvious consensus regarding prognostic factors for ESS.

Since 1988, uterine sarcomas including ESS had been staged by the same staging system as uterine corpus carcinoma. In 2009, the International Federation of Gynecologists and Obstetricians (FIGO) introduced a distinct staging system for leiomyosarcoma and ESS, and some studies have validated the new staging system for these tumors [10], [11].

Therefore, the aim of this multicenter study was to enhance understanding of ESS and to assess the prognostic factors associated with overall survival (OS), recurrence-free survival (RFS), and survival after recurrence in ESS by applying the 2009 FIGO staging system.

Section snippets

Study population

This multicenter retrospective study included patients with ESS (formerly low-grade endometrial stromal sarcoma) who were treated at the Samsung Medical Center (SMC, Seoul, Republic of Korea) and Asan Medical Center (AMC, Seoul, Republic of Korea). From January 1990 to January 2012, data of patients in whom ESS was diagnosed were collected from the electronic medical records under institutional review board approval at both institutions. We only included patients with low-grade tumors who had

Results

During this study period, a total of 117 patients with ESS were identified. Three patients were excluded because of concomitant gastric cancer (one patient) and correction of the histologic type to undifferentiated uterine sarcoma (two patients) by review of the pathology slides. The remaining 114 patients were included in the study.

Baseline characteristics of these patients are presented in Table 1. The median age at diagnosis of patients was 45 years (range: 18–74). Of the 114 patients, 88

Discussion

This study is one of the largest cohorts of homogenous ESS describing the prognostic factors with a comprehensive review of the clinical course of the disease according to the 2009 FIGO staging system. In this study we found that BSO was independently associated with good recurrence-free survival in patients with ESS. Particularly, in the premenopausal patients, BSO was significantly associated with longer RFS. In addition, patients who underwent cytoreductive resection of recurrent ESS

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system.
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The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease.
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LG-ESS has low metastasis rate. Surgical modalities and neoadjuvant therapies are recommended base on the stage of ESS. In the following study, we represent a case of incidental LG-ESS with bilateral ovarian invasion who was initially diagnosed as an ovarian mass.
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Citation Excerpt :
While some studies reported lymphadenectomy as an independent predictor of improved survival [11,12], others failed to show any impact of lymphadenectomy on disease outcomes [3,21,22]. LN metastasis in LGESS has been reported to range from 6.6% to 16.6% in previous studies [3,10,19], which was 14.8% in our study. Similar to studies of endometrial carcinoma [23,24], we found that more than a half of patients (75%) with pelvic LN metastasis had positive paraaortic LNs.
To investigate factors associated with refractory disease, recurrence, or death as well as disease-free survival (DFS) and overall survival (OS) in low-grade endometrial sarcoma (LGESS).
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¹: Contributed equally to this work.

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Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conflict of interest statement

Gynecol Oncol

Crit Rev Oncol Hematol

Ann Oncol

Gynecol Oncol

Ann Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Int J Gynaecol Obstet

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Eur J Obstet Gynecol Reprod Biol