Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience

doi:10.1016/j.ygyno.2017.08.021

Gynecologic Oncology

Volume 147, Issue 2, November 2017, Pages 315-319

https://doi.org/10.1016/j.ygyno.2017.08.021 Get rights and content

Highlights

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Modern stage II endometrial cancer is defined only by cervical stromal invasion.
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Patients received surgical staging and adjuvant radiation with or without chemo.
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Five-year rates of disease-free and overall survival were 68% and 75%.
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The primary mode of disease recurrence was distant metastases.
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Our data suggests recurrence risk may depend on radiation modality.

Abstract

Purpose

Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion.

Materials and methods

Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990–2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test.

Results

110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT ± BT, with 13.6% receiving BT alone. With a median follow-up of 64.6 months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy.

Conclusions

This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases.

Introduction

Endometrial cancer remains the most prevalent female gynecologic malignancy, comprising 7% of new cancer cases in the US in 2017 [1]. Cancer staging is a critical part of management, allowing for proper risk stratification and determination of primary and adjuvant treatments. Comprehensive surgical staging is the current standard of care for endometrial cancer, typically involving simple hysterectomy and bilateral salpingo-oophorectomy, with persisting debate over the benefit of lymph node dissection [2], [3]. The most widely used system for surgical staging was initially defined by the Féderation Internationale de Gynécologie et d'Obstétrique (FIGO) in 1988. In the most recent FIGO annual report on endometrial cancer in 2006, 12% of surgically staged endometrial cancer patients were found to present with stage II disease [4].

FIGO staging of endometrial cancer was revised in 2009 to more accurately reflect the limited prognostic impact of cervical glandular involvement, and stage II disease was defined as cervical stromal invasion only [5]. This revision comes with a need for re-evaluation of appropriate management, as there is currently a paucity of data available on this updated population. Prior studies on stage II endometrial cancer were limited by a majority of cases having glandular invasion without stromal involvement, potentially inflating outcomes more so than those with the modern definition of stage II disease [6], [7], [8], [9].

Following surgery, current options for adjuvant radiation treatment of stage II endometrial cancers include external beam radiation therapy (EBRT), vaginal brachytherapy (BT), or a combination of the two. Several large randomized studies, including GOG 99 and ASTEC, have shown that EBRT is superior to no treatment in reducing the risk of pelvic recurrences in stage I and II endometrial cancers [9], [10]. In accordance with these findings, guidelines recommend the use of adjuvant radiation for the prevention of locoregional recurrence [4], [11]. The 2014 ASTRO guidelines recommend adjuvant EBRT with BT for stage II endometrial cancer, with the possibility for BT alone if ≥ 10 lymph nodes were dissected and negative [12], [13]. However, there are no randomized trials comparing radiation modalities specifically for disease with cervical stromal involvement, and existing randomized trials have included few patients with modern stage II cancer.

The purpose of this study is therefore to evaluate recurrence patterns, overall survival, and the impact of adjuvant therapy in women with modern stage II endometrial cancer who underwent surgical staging and treatment.

Section snippets

Materials and methods

In this IRB-approved study, we retrospectively identified patients diagnosed with endometrial cancer at UPMC Hillman Cancer Center institutions between 1990 and 2013. All of the patients analyzed had surgically staged 2009 FIGO stage II disease, defined as cervical stromal invasion. Surgical staging involved a minimum of simple hysterectomy ± lymph node dissection, while radical hysterectomy was only performed for patients with clinically overt stage II disease. Pathology reports were reviewed

Patient characteristics

Among 1412 patients diagnosed with endometrial cancer, 110 (7.8%) patients with 2009 FIGO stage II disease were identified with a median age of 64 years. Patient characteristics are summarized in Table 1. All underwent surgical staging with 91.4% of patients and 8.6% of patients undergoing simple and radical/modified radical hysterectomy, respectively. FIGO grade distribution was as follows: 23.6% were grade 1, 39.1% were grade 2, and 37.3% were grade 3/adverse histology. The most common subtype

Discussion and conclusions

For endometrial cancer, stage II disease is an uncommon presentation, with estimated prevalence likely below 12% given the exclusion of cervical glandular involvement in modern 2009 FIGO staging [4]. Thus, most prospective trials on adjuvant treatment for endometrial cancer have elected to lump stage II patients in with stage I patients. In ASTEC, < 1% of patients had cervical stromal involvement [10]. Only 9% of patients in GOG 99 had stage II disease, with no differentiation made between

Declaration

Data were presented as an oral presentation at the 2016 American Society for Radiation Oncology (ASTRO) annual meeting in San Antonio, TX.

Conflicts of interest notification

Acute or potential conflict of interest does not exist.

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Adjuvant Radiotherapy in Stage II Endometrial Cancer: Selective De-intensification of Adjuvant Treatment
2023, Clinical Oncology
Citation Excerpt :
For stage II with POLE mutation, there is guideline support to considering omission of adjuvant therapy, which is even further de-escalation than explored in the current study population [19]. Most patients in the current study were treated with FP-EBRT + VBT, in line with other retrospective studies [14,17]. MP-EBRT ± VBT boost was only used at one of the regional centres.
Risk stratification, including nodal assessment, allows for selective de-intensification of adjuvant radiotherapy in stage II endometrial cancer. Patterns of treatment and clinical outcomes, including the use of reduced volume ‘mini-pelvis’ radiotherapy fields, were evaluated in a population-based study.
All patients diagnosed with pathological stage II endometrial cancer between 2000 and 2014, and received adjuvant radiotherapy in a regional healthcare jurisdiction were reviewed. Registry data were supplemented by a comprehensive review of patient demographics, disease characteristics and treatment details. The Charlson Comorbidity Score was calculated. Survival and recurrence data were analysed.
In total, 264 patients met the inclusion criteria. Most patients had endometrioid histology (83%); 41% of patients had International Federation of Gynecologists and Obstetricians grade 1 disease. Half (49%) had surgical nodal evaluation; 11% received chemotherapy. Most patients (59%) were treated with full pelvic radiotherapy fields ± brachytherapy. Seventeen per cent of patients received mini-pelvis radiotherapy ± brachytherapy, whereas 24% received brachytherapy alone. Five-year recurrence-free survival was 87% for the entire cohort, with no significant difference by adjuvant radiotherapy approach. Only one patient receiving mini-pelvis radiotherapy ± brachytherapy recurred in the pelvis but outside of the mini-pelvis field. Recorded late toxicity rates were highest for full pelvis radiotherapy + brachytherapy.
Risk stratification in a real-world setting allowed for selective de-intensification of adjuvant radiation with equivalent outcomes for stage II endometrial cancer. Mini-pelvis radiotherapy combined with brachytherapy is effective in highly selected patients, with the potential to decrease toxicity without compromising local control. Brachytherapy should be considered in low-risk stage II patients.
Vaginal brachytherapy alone for patients with Stage II endometrial cancer with inner half cervical stromal invasion
2019, Brachytherapy
Citation Excerpt :
There are now several series in the literature supporting conservative management for patients with Stage II endometrial cancer with favorable pathologic features. Low rates of recurrence with use of VB alone have been reported in single- and multi-institutional series (9–14,16,19,20). Reported risk factors for recurrence are similar to those for Stage I disease and include age, grade, depth of myometrial invasion, LVSI, and completeness of nodal dissection.
The purpose of this study was to review outcomes of women with Stage II endometrial carcinoma with inner half cervical stromal invasion treated with adjuvant vaginal brachytherapy (VB) alone.
A single-institution retrospective chart review identified consecutive patients with Stage II endometrial cancer and inner half cervical stromal invasion treated with VB alone from 2011 to 2015. Patients who received chemotherapy or external beam radiotherapy were excluded. Patient and disease characteristics were collected. Association between variables and outcomes were assessed using Fisher's exact or Wilcoxon rank sum test.
Fifty-seven patients were identified over 5 years with a median followup of 46.8 months. Carcinoma was endometrioid Grade 1 (43.9%), 2 (36.8%), 3 (5.3%), or serous (14.0%). Depth of myometrial invasion was inner half in 75.4%. Lymphovascular invasion was seen in 28.1%, and lymph node assessment was performed in 43.9% of patients. The median depth of cervical stromal invasion was 1.25 mm (n = 48 patients). The median percentage of the cervical stromal wall invaded by tumor (obtained in 40 patients) was 16.7%. Seven (12.3%) patients recurred at a median of 16.9 months. Five-year estimates of progression-free survival and overall survival were 81.5% and 78.5%, respectively. The only factor associated with recurrence, progression-free survival or overall survival on bivariate analysis was high-grade (Grade 3 or serous) disease (p = 0.031).
VB alone can be considered for Stage II patients with inner half cervical stromal invasion and Grade 1–2 disease. Systemic therapy may be required for patients with Grade 3 and serous histology as 75% (3/4) of these recurrences were outside the pelvis.
The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study
2018, Brachytherapy
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Given the increasingly recognized role of systemic treatment in node-positive patients (5), these studies failed to answer the question of optimum radiation therapy treatment regimens or treatment type for Stage II disease. Few studies to date have evaluated the role of radiation therapy for this subset of patients, although retrospective series suggest that BT alone may be sufficient for this patient population (6–10). One of the largest retrospective studies in this population shows that vaginal BT offers local control rates comparable to that offered by BT and EBRT with lower rates of toxicity (7, 10).
The optimum adjuvant treatment for Stage II endometrial cancer patients is unknown. External beam radiation therapy (EBRT) is often considered the standard of care; however, retrospective series suggest that brachytherapy (BT) alone may be sufficient for selected patients. As randomized data are lacking, we used a large database to explore this question.
The National Cancer Data Base was queried for patients with pathologic International Federation of Gynecology and Obstetrics Stage II disease. Demographic, clinic-pathologic, and treatment details were compared between patients. Multivariable analysis was used to determine factors associated with receiving radiation therapy (RT). To account for imbalances between groups, a matched-pair analysis was completed.
Eight thousand one hundred forty patients were included. RT was associated with overall survival (OS), with EBRT (hazard ratio [HR] 0.64), BT (HR 0.47), and combination (HR 0.54) showing increased OS on univariate analysis. Facility, urban location, diagnosis year, hysterectomy type, and chemotherapy did not reach significance. On multivariate analysis, RT was associated with OS, with EBRT (HR 0.69), BT (HR 0.60), and combination (HR 0.54) showing benefit. Using propensity-score matching, RT continued to show improved OS regardless of type: BT (82% vs. 73% 5-year OS) and EBRT (77% vs. 71%). BT as compared to EBRT had equivalent survival (81% vs. 79%, not statistically significant).
This study of over 8,000 patients demonstrates that adjuvant RT confers a survival benefit in Stage II endometrial cancer and supports the continued use of RT in these patients. BT alone may be reasonable in carefully selected patients.
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A population-based study of outcomes in adjuvant radiotherapy for stage II endometrial carcinoma
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Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience

Highlights

Abstract

Purpose

Materials and methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Patient characteristics

Discussion and conclusions

Declaration

Conflicts of interest notification

Am. J. Obstet. Gynecol.

Int. J. Gynaecol. Obstet.

Int. J. Gynaecol. Obstet.

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Ann. Oncol.

Pract. Radiat. Oncol.

Adv. Radiat. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.