Sentinel node biopsy for the management of early stage endometrial cancer: Long-term results of the SENTI-ENDO study

doi:10.1016/j.ygyno.2014.09.011

Gynecologic Oncology

Volume 136, Issue 1, January 2015, Pages 54-59

https://doi.org/10.1016/j.ygyno.2014.09.011 Get rights and content

Highlights

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Long-term results of SENTI-ENDO evaluating the impact of sentinel lymph node biopsy on endometrial cancer management and survival
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No difference in RFS according to SLN status was observed.
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The relevance of SLN biopsy on surgical management and indications for adjuvant therapies should be confirmed.

Abstract

Objective

We report the long-term results of the SENTI-ENDO study evaluating the impact of sentinel lymph node (SLN) biopsy on management and survival in patients with early stages of endometrial cancer (EC).

Methods

Patients with FIGO stage I–II EC underwent pelvic SLN biopsy after cervical dual injection (technetium and patent blue) and systematic pelvic node dissection. This study is a secondary endpoint reporting the long-term recurrence free survival (RFS) and the impact of the SLN procedure on adjuvant therapies.

Results

The median follow-up was 50 months (range: 3–77 months). Eighteen of the 125 patients (14.4%) experienced a recurrence. The 50-monthrecurrence-free survival (RFS) was 84.7% with no difference between patients with and without detected SLN (p = 0.09). Among patients with detected SLN (111), no difference in RFS was observed between those with and without positive SLN (p = 0.5). In the whole population, adjuvant therapy was performed in low-, intermediate- and high-risk groups in 31 of 64 patients (48.4%), 28 of 37 patients (75.7%) and 14 of 17 patients (82.3%), respectively (p = 0.0001). For the 111 patients with detected SLN, EBRT was performed in 27 of the 89 with negative SLN and in 11 of the 14 with positive SLN (p = 0.001). Chemotherapy was performed more frequently in patients with positive SLN (6/12, 50%) than in patients with negative SLN (7/56, 12.5%) (p = 0.009).

Conclusions

Our results support the impact of SLN biopsy on surgical management and indications for adjuvant therapies. Further studies are required to assess the clinical impact of the SLN biopsy in early stage EC.

Introduction

Endometrial cancer (EC) is the most frequent gynecological cancer in developed countries [1]. In France, more than 6500 new cases are diagnosed each year with an incidence similar to that observed in other European countries (UK), representing the seventh most common cause of death from cancer in women in western Europe [2].

At diagnosis, about three-quarters of patients with EC have disease confined to the uterine corpus. Classic management of early stages of EC is based on hysterectomy, bilateral salpingo-oophorectomy and pelvic +/− para-aortic lymphadenectomy [3]. Indications for adjuvant therapies depend on uterine findings and lymph node status [4]. Histological characteristics are recognized as being independent prognostic factors for survival and have given rise to the identification of three risk groups of relapse according to histology (type 1: endometrioid carcinoma, type 2: carcinosarcoma, clear cell or serous papillary carcinoma), tumor grade and depth of myometrial invasion [3], [5]. The five-year overall survival is 75% for all FIGO stages, and as high as 95% for early stages confined to the uterus.

Recently, two trials and a meta-analysis have been published suggesting that pelvic lymphadenectomy has no impact on overall and disease-free survivals in patients with early stage EC while exposing patients to the risk of complications [6], [7], [8]. However, these results have been discussed in light of studies demonstrating that pelvic and para-aortic lymphadenectomy is associated with longer overall survival for patients with intermediate- or high-risk EC [9]. Moreover, none of these data took into account the contribution of sentinel lymph node (SLN) biopsy in improving metastasis detection through ultrastaging [10]. Indeed, in a multicenter study evaluating the contribution of SLN biopsy in early stage EC, 17% of women had lymph node metastasis suggesting that SLN biopsy adds significant data to uterine findings to tailor adjuvant therapy [11]. Finally, Kitchener concluded that SLN biopsy could be a trade-off between systematic lymphadenectomy and no lymphadenectomy [12]. However, the impact of SLN biopsy on surgical management and indications for adjuvant therapies, and hence potentially on recurrence, has been poorly investigated to date. We report the long-term results of a prospective multicenter study on SLN biopsy in patients with early stages EC (SENTI-ENDO).

Section snippets

Patients and methods

This prospective study was approved by our Institutional Review Committee (Ile de France 1, CPP 0711481) and registered on ClinicalTrials.gov under NCT00987051. From July 2007 to August 2009, all patients with EC seen at one of the nine participating centers were considered for enrollment. Inclusion criteria were: endometrial carcinoma confirmed by biopsy, patients over 18 years affiliated to the French Health Care System and speaking and reading French, invasive cancers (FIGO stages I and II

Adjuvant therapies and follow-up

Based on definitive histology, three risk groups according to the ESMO guidelines for EC were defined as follows [3]: low risk (type 1 EC, stage IA grade 1 or 2); intermediate risk (type 1 EC, stage IA grade 3, or stage IB grade 1 or 2); and high risk (type 1 EC, stage IB grade 3, or type 2 EC of any stage and grade). For patients with low-risk EC, no adjuvant therapy was recommended. For patients with intermediate-risk EC, a vaginal brachytherapy (VBT) was recommended. For patients with

Impact of SLN biopsy on surgical management and adjuvant therapies

Among the 125 patients included in the study, preoperative assessment of EC risk groups was available in 82 (65.6%). Preoperative histological grade was not available in 43 cases (mainly due to insufficient tissue in Pipelle endometrial sampling). Among these patients, the number of patients with low-, intermediate- and high-risk EC was 35, 24 and 23 (64 type 1 and 18 type 2 EC), respectively. Ten of the 23 patients with high-risk EC underwent a systematic PAAL (Table 1).

Three (33.3%) of the

Discussion

Despite the publication of two randomized trials showing that there is no advantage in performing systematic lymphadenectomy in patients with early stage EC, there is persistent debate about the relevance of including lymphadenectomy in standard management of EC [6], [7], [8], [11], [12]. In our first report, we demonstrated that SLN biopsy adequately predicts lymph node status especially for patients with type 1 EC and that lymph node involvement was more accurately detected by ultrastaging

Role of the funding source

The SENTI-ENDOstudy was funded by a grant from the Programme Hospitalier de Recherche Clinique PHRC 2006 (Ministère de la Santé), and sponsored by “Assistance publique — Hôpitaux de Paris”. Data was collected by the Unité de Recherche Clinique de l'Est Parisien (URCEST: TS, NM, IZ, SB, FA), and analyzed and interpreted independently. The report writing was led by ED. The corresponding author had full access to all of the data and the final responsibility to submit for publication. All authors

Conflict of interest statement

All authors confirm that they have no conflict of interest.

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To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC).
We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling.
Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups.
Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.
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The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades.
Mapping sentinel lymph nodes in early-stage ovarian cancer (MELISA) trial - a further step towards lymphadenectomy replacement
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Sistematic pelvic and para-aortic lymphadenectomy is part of the staging surgery for early-stage epithelial ovarian cancer, with no therapeutic value. The Mapping Sentinel Lymph Nodes In Early-Stage Ovarian Cancer (MELISA) trial prospectively assessed the SLN detection rate and the diagnostic accuracy of the SLN mapping technique in patients with early-stage epithelial ovarian cancer.
This prospective, single-arm study included patients diagnosed with early-stage epithelial ovarian cancer (FIGO stages I and II), via either primary surgery or re-staging surgery. SLN mapping was performed by injecting 0.2 mL of 37-mBq ^99mTc-nanocoloid albumin and 2 mL of 2.5 mg/mL indocyanine green into the infundibulopelvic and utero-ovarian ligaments. After removal of SLNs, a complete systematic pelvic and para-aortic lymphadenectomy was performed. SLN Ultrastaging analysis was applied. The primary outcome was the overall SLN detection rate, either with one or both tracers. Secondary outcomes were the diagnostic accuracy of detecting lymph node metastases and factors that may influence SLN detection.
Thirty patients were included. SLNs were identified in 27 patients (90%). Detection rates in primary and re-staging surgery were 89% and 92%, respectively. Para-aortic drainage was the predominant lymphatic spread, observed in 26 of 27 patients. Ultrastaging pathologic reports listed 1 SLN with macrometastasis, 1 with micrometastasis, and 5 with isolated tumor cells; the sensitivity of SLN mapping was 100%, with a false-negative rate of 0%. Univariate analysis showed a nonsignificant higher proportion of patients with uterine fibroids, adenomyosis, and endometriosis (100%, 67%, 67%, respectively) in patients in whom SLNs were not detected.
SLN mapping has a high detection rate (90%) and is an accurate technique for detecting lymph node involvement in early-stage epithelial ovarian cancer. SLN mapping is a potential alternative to systematic lymphadenectomy to reduce associated morbidity, but further research is needed to evaluate the impact of SLN mapping on oncologic outcomes and its cost-effectiveness.
Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy
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The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/− para-aortic lymphadenectomy (LND).
Patients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC).
Out of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3–84.0%) in the SLN group and 71.3% (95% CI 62.0–78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56–2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47–2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1–93.7%) in the SLN group and 95.1% (95% CI 89.4–97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39–10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94–8.95, p = 0.06).
There was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.
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Sentinel node biopsy for the management of early stage endometrial cancer: Long-term results of the SENTI-ENDO study

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Adjuvant therapies and follow-up

Impact of SLN biopsy on surgical management and adjuvant therapies

Discussion

Role of the funding source

Conflict of interest statement

Rev Dépidémiologie Santé Publique

Ann Oncol Off J Eur Soc Med Oncol ESMO

Eur J Obstet Gynecol Reprod Biol

Gynecol Oncol

Lancet

Gynecol Oncol

Lancet Oncol

Lancet Oncol

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol