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