Elsevier

Gynecologic Oncology

Volume 113, Issue 3, June 2009, Pages 316-323
Gynecologic Oncology

Stage II endometrioid adenocarcinoma of the endometrium: Clinical implications of cervical stromal invasion

https://doi.org/10.1016/j.ygyno.2009.03.007Get rights and content

Abstract

Objectives

Endometrioid adenocarcinoma of the endometrium (EEC) is the most common histologic type of endometrial cancer, with stage being the most critical prognostic factor. Cervical involvement (CI), divided into IIA (epithelial involvement) and IIB (stromal invasion), is overall associated with decreased survival (70 vs 90%). However, the impact on prognosis of sub-stages IIA vs IIB is unclear. The purpose of this study was to investigate the prognostic significance of cervical involvement as well as its substaging in patients diagnosed with EEC.

Methods

Eighty-one patients treated for stage II EEC were identified (1993–2003) in our institution. They were stratified into Group 1 (46) with available slides for review and Group 2 (35) with information obtained from the pathology report. All pathology reports, for all 81 patients, contained information on cervical glandular and stromal involvement. In Group 1, 1 to 6 slides of cervix (mean 3) were reviewed. Tumors were classified as Stage IIA or IIB according to the most recent FIGO criteria. Stromal invasion (SI) in Group 1 tumors was sub-classified in 4 subgroups based on depth of invasion; A) ≤ 1 mm; B) > 1 mm and ≤ 3 mm; C) > 3 mm and ≤ 5 mm and D) > 5 mm. Other histopathologic parameters evaluated include grade, depth of myometrial invasion (MI), and lymphovascular invasion (LI). Clinical data included age, type of surgery, type of radiation, and survival. Statistical analysis was performed.

Results

Patients ranged in age from 33–91 (median 64) years. In Group 1, 11 patients had stage IIA and 35 stage IIB tumors. Depth of SI ranged from 1–12 mm (mean 3.4 mm). The pathologists reviewing the slides in Group 1 agreed with the initial reported description of cervical glandular and stromal involvement. In Group 2, 15 patients had stage IIA and 20 stage IIB tumors with no further information regarding depth of SI. In Group 1, 12 EECs were Grade 1, 29 Grade 2, and 5 Grade 3. Thirty tumors had < 50% MI, 15 showed > 50% MI and LVI was present in 11. In Group 2, 13 tumors were Grade 1, 13 Grade 2, and 9 Grade 3. Twenty-one had < 50% or no MI and 9 showed LVI. Median follow-up was 73 (range 5–210) months. Five- and 10-year survival rates were 83% and 78% for patients with stage IIA and 71% and 65% for stage IIB EECs respectively. By univariate analysis, age, MI, LVI and type of treatment affected survival but not substaging into IIA vs IIB or depth of SI. By multivariate analysis, only age (p = 0.001), LVI (p = 0.017), and type of treatment (p = 0.022) were predictors of survival in stage II EECs.

Conclusions

This study showed that the distinction between stage IIA and IIB or depth of SI does not affect survival in patients with EEC. LVI and type of hysterectomy performed were predictors of survival in stage II EECs. Our results suggest that substaging should be eliminated, women with suspect cervical SI should be offered a radical hysterectomy, and that the presence of LVI may be a useful tool in guiding recommendations about the need for adjuvant radiation therapy.

Introduction

Endometrial cancer is the most common female gynecologic cancer in the United States, and the second most common among women living in the Western world [1]. The International Federation of Gynecology and Obstetrics (FIGO) introduced a major modification to the staging system in endometrial cancer 20 years ago, changing it from a clinical to a surgical staging system. Parameters included are depth of myometrial invasion, cervical involvement as well as extrauterine extension [2]. Other parameters not related to staging but that have also been proved to have prognostic significance include histologic grade, histologic type, lymphovascular invasion among others [2]. While patients with low-grade endometrial cancers confined to the uterine corpus (Stage I) usually have good prognosis with an estimated 5-year survival rate exceeding 90%, in patients with high grade tumors or with tumors showing deep myometrial and/or lymphovascular invasion the 5-year survival rates may be as low as 40% [3], [4], [5], [6].

In approximately 10% of patients, endometrial carcinoma (6–20% in different series) involves the uterine cervix. These patients have an estimated 70% 5-year survival rate [7]. However, there is a relative lack of consensus as to what represents the most appropriate management strategy for these patients; simple extrafascial vs radical hysterectomy; role and type of radiation therapy (brachytherapy alone, teletherapy alone, teletherapy and brachytherapy combined), and use of pre-operative radiation therapy for occult Stage II disease. The literature is flawed with controversy, largely because: 1) most studies are retrospective and have included patients whose tumors were not comprehensively staged to fulfill FIGO criteria; 2) studies have been often multi-centered; and 3) they have included patients with clinical but not surgical Stage II tumors. The infrequent occurrence of cervical involvement by endometrial carcinoma has made it impossible to accrue enough patients to study these different management strategies prospectively. Finally, no studies have focused on the clinical validity of stage II subdivision, IIA vs IIB, to the best of our knowledge.

The purpose of this study was to investigate the prognostic significance of cervical involvement in patients diagnosed with endometrioid endometrial adenocarcinoma (EEC). Specifically, we aimed to further investigate the potential role of depth of cervical stromal invasion, and to correlate these findings with histologic grade, myometrial invasion and lymphovascular invasion, parameters closely related to survival in patients with EEC. Herein, we present a single institutional series of patients with Stage IIA and IIB EEC, whose tumors were similarly staged and treated by one of six gynecologic oncologists, and whose radiation therapy, if administered, was delivered by one of three radiation oncologists from the assumed institution. We intend to report on surgical, pathologic, and therapeutic factors for both Stage IIA and IIB EECs, as well as other important clinical outcomes, such as complications from single vs dual modality therapies, patterns of recurrence and survival.

Section snippets

Materials and methods

After protocol approval by the Institutional Review Board (IRB) we searched the Cancer Registry for all women diagnosed and treated for FIGO Stage II EEC at the Massachusetts General Hospital between 1993 and 2003.

All pathology reports were reviewed. Patients were stratified into Group 1, if slides were available for re-review or Group 2 if information was obtained from the pathology report. Re-review of archival material was performed by two independent pathologists (EO and SS). In these

Clinical findings

Between 1993 and 2003, a total of 1485 patients with endometrial cancer were diagnosed and treated at our institution. FIGO Stage II tumors represented 10.4% (n = 142) of the overall group and of those, EECs constituted 70% (n = 98). Three patients underwent pre-operative radiation therapy, one patient died before surgical treatment and 13 additional patients had a second gynecologic or non-gynecologic primary malignant tumor and were excluded from the study. The patients' tumors were similarly

Discussion

We report a series of patients with FIGO surgicopathologically designated stage II EEC treated at our institution. In this study, the distinction between stage IIA and IIB or depth of SI does not affect survival in patients with EEC. However, LVI and type of hysterectomy performed had an impact on survival. In this series, the percentage of patients with stage II tumors (10.4%) is in agreement with the findings reported in the literature [4]. However, in contrast to many previous studies, all

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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