Elsevier

Gynecologic Oncology

Volume 146, Issue 2, August 2017, Pages 405-415
Gynecologic Oncology

Review Article
Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations

https://doi.org/10.1016/j.ygyno.2017.05.027Get rights and content

Highlights

  • SLN mapping compared to staging lymphadenectomy in EC may reduce morbidity.

  • Literature-based recommendations for the inclusion of SLN assessments are presented.

  • History and various techniques of SLN mapping in endometrial cancer are described.

  • Pathology and clinical outcomes from SLN assessment are reviewed.

  • Controversies and future directions for research in SLN assessment are discussed.

Abstract

The emphasis in contemporary medical oncology has been “precision” or “personalized” medicine, terms that imply a strategy to improve efficacy through targeted therapies. Similar attempts at precision are occurring in surgical oncology. Sentinel lymph node (SLN) mapping has recently been introduced into the surgical staging of endometrial cancer with the goal to reduce morbidity associated with comprehensive lymphadenectomy, yet obtain prognostic information from lymph node status. The Society of Gynecologic Oncology's (SGO) Clinical Practice Committee and SLN Working Group reviewed the current literature for preparation of this document. Literature-based recommendations for the inclusion of SLN assessment in the treatment of patients with endometrial cancer are presented. This article examines:

  • History and various techniques of SLN mapping in endometrial cancer

  • Pathology and clinical outcomes from SLN assessment

  • Controversies and future directions for research in SLN assessment in endometrial cancer.

Introduction

Endometrial cancer is the most common gynecologic cancer in North America, and worldwide there are approximately 320,000 cases diagnosed annually. Following the Federation of International Gynecology and Obstetrics (FIGO) adoption of surgical staging in 1988, pathology that includes information about the primary tumor as well as lymph node status has guided prognosis and use of adjuvant therapies. Surgical staging is associated with risks of lymphedema, lymphocysts, cellulitis, and damage to nearby nerves. Sentinel lymph node (SLN) assessment has been proposed as a more “targeted” alternative to complete pelvic lymphadenectomy in an effort to secure information about lymph node status for treatment planning, yet minimize collateral damage. The purpose of this article is to review the current literature regarding SLN assessment in endometrial cancer and to improve outcomes for women with this disease.

Section snippets

History of endometrial cancer surgical staging

The value of staging patients with cancer lies in the ability to assess prognosis, plan therapy, and facilitate communication between health care providers. Surgical staging also serves as a research tool to assess treatments among patient groups and for stratification in clinical trials. Prior to 1950, staging endometrial cancer was quite variable between institutions and expert gynecologists. Following the success of standardized staging for cervical cancer in the 1950s, FIGO assumed

History of SLN mapping

Although the orderly progression of lymphatic metastases has been hypothesized for several hundred years, the first report of SLN mapping success was in 1977, using lymphangiography of the penis [12]. The reproducibility of SLN mapping with radiocolloid for patients with cutaneous melanomas quickly followed, but was not more widely accepted until blue dyes emerged as a way to augment radiotracers in the late 1980s [13]. Since then, SLN mapping techniques have been developed for several other

Colorimetric methods

Colorimetric lymphatic mapping refers to the visual detection of lymph channels and nodes using colored dyes in white light. This technique requires the least complex equipment and is applicable to open, laparoscopic, and robotic approaches.

Isosulfan blue is FDA approved for lymphatic mapping. Typically, 3–5 cm3 of a 1% solution are injected into the cervix, after which there is immediate uptake of the dye into lymphatic channels and accumulation in the SLNs within 10–20 min. Delay from injection

SLN pathology

“Ultrastaging” refers to the utilization of enhanced pathology techniques, including deeper serial sections and immunohistochemical (IHC) stains, to increase the detection of malignant cells in SLNs [65]. Strategies for the pathologic processing of SLNs, including the number of level sections examined by routine hematoxylin and eosin (H&E) staining, the depth of sectioning into the tissue block, the interval of microns (μms) between sections, and the use of IHC to identify tumor cells not noted

SLN mapping in endometrial cancer

Several observational studies of SLN mapping in endometrial cancer using either single dyes, combinations of dyes, or Tc-99 radiocolloid injected into the cervix have been reported (Table 1, Table 2) [30], [32], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58]. The reproducibility of the cervical injection technique, high success rate, and low-risk for isolated aortic metastasis has led most

Controversies IN SLN mapping for endometrial cancer

While the current information from SLN mapping studies in endometrial cancer appear quite promising, there are many controversies. The accuracy of the technique across practitioners, appropriate patient selection, optimal treatment algorithm to differentially manage high- and low-grade patients, the role of para-aortic dissection, and the clinical significance of ITC node metastasis require further research.

Future directions

The NCCN SLN mapping algorithm holds great promise as a modern staging strategy for apparent uterine-confined endometrial carcinoma [80]. While awaiting the launch of randomized surgical trials that include an SLN component, several NCI-designated United States cancer centers have embarked on collaborative SLN studies of their endometrial cancer databases, and the results continue to be analyzed. For example, in a comparison of patient cohorts from two separate institutions, the validity of the

Consensus recommendations

Based on the current literature, we recommend that:

  • 1.

    For patients with endometrial cancer, SLN mapping by cervical injection of tracers accurately predicts the presence of pelvic lymph node metastasis and has a low (< 5%) false-negative rate when the NCCN surgical algorithm is closely followed. It is recommended that completion lymphadenectomy be performed as an “add on” until an individual surgeon's experience documents literature-comparable success of SLN detection and a < 5% false-negative rate.

  • 2.

Conflict of interest statement

We declare that there are no direct conflicts of interest associated with this manuscript, except the following relationships:

  • Dr. Holloway reports personal fees from Intuitive Surgical, Inc., outside the submitted work;

  • Dr. Boggess reports personal fees from Intuitive Surgical, Inc., outside the submitted work;

  • Dr. Lowery reports personal fees from AstraZeneca, Inc., outside the submitted work.

References (97)

  • D. Albo et al.

    Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer

    Am. J. Surg.

    (2001)
  • W.D. Blessing et al.

    A comparison of methylene blue and lymphazurin in breast cancer sentinel node mapping

    Am. J. Surg.

    (2002)
  • M. Ballester et al.

    Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)

    Lancet Oncol.

    (2011)
  • A. Perissinotti et al.

    Use of SPECT/CT for improved sentinel lymph node localization in endometrial cancer

    Gynecol. Oncol.

    (2013)
  • E.L. Jewell et al.

    Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies

    Gynecol. Oncol.

    (2014)
  • E.C. Rossi et al.

    Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study

    Gynecol. Oncol.

    (2012)
  • R.W. Holloway et al.

    Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging: a comparison of colorimetric and fluorescence imaging

    Gynecol. Oncol.

    (2012)
  • A.K. Sinno et al.

    A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer

    Gynecol. Oncol.

    (2014)
  • E.J. Tanner et al.

    Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer

    Gynecol. Oncol.

    (2015)
  • J.N. Barlin et al.

    The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes

    Gynecol. Oncol.

    (2012)
  • J.F. Delaloye et al.

    Intraoperative lymphatic mapping and sentinel node biopsy using hysteroscopy in patients with endometrial cancer

    Gynecol. Oncol.

    (2007)
  • P.H. Desai et al.

    Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC)

    Gynecol. Oncol.

    (2014)
  • J. How et al.

    Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer

    Gynecol. Oncol.

    (2015)
  • J. How et al.

    Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study

    Gynecol. Oncol.

    (2012)
  • H. Niikura et al.

    Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer

    Gynecol. Oncol.

    (2013)
  • M. Plante et al.

    Sentinel node mapping with indocyanine green and endoscopic near-infrared fluorescence imaging in endometrial cancer. A pilot study and review of the literature

    Gynecol. Oncol.

    (2015)
  • E. Solima et al.

    Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer

    Gynecol. Oncol.

    (2012)
  • A. Torne et al.

    Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): a new method for sentinel lymph node detection in endometrial cancer

    Gynecol. Oncol.

    (2013)
  • O. Touhami et al.

    Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer

    Gynecol. Oncol.

    (2015)
  • J. Mucke et al.

    Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results

    Gynecol. Oncol.

    (2014)
  • T.W. Burke et al.

    Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer: results of a pilot study

    Gynecol. Oncol.

    (1996)
  • A.M. Perrone et al.

    Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer

    Gynecol. Oncol.

    (2008)
  • N.R. Abu-Rustum et al.

    Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma?

    Gynecol. Oncol.

    (2009)
  • E.C. Rossi et al.

    A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study

    Lancet Oncol.

    (2017)
  • R.W. Holloway et al.

    Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis

    Gynecol. Oncol.

    (2016)
  • E. Raimond et al.

    Impact of sentinel lymph node biopsy on the therapeutic management of early-stage endometrial cancer: results of a retrospective multicenter study

    Gynecol. Oncol.

    (2014)
  • S. Kang et al.

    Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies

    Gynecol. Oncol.

    (2011)
  • F. Khoury-Collado et al.

    Improving sentinel lymph node detection rates in endometrial cancer: how many cases are needed?

    Gynecol. Oncol.

    (2009)
  • M.M. Leitao et al.

    Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer

    Gynecol. Oncol.

    (2013)
  • J. Ehrisman et al.

    Performance of sentinel lymph node biopsy in high-risk endometrial cancer

    Gynecol. Oncol. Rep.

    (2016)
  • B. Hagen et al.

    Indocyanine green fluorescence imaging of lymph nodes during robotic-assisted laparoscopic operation for endometrial cancer. A prospective validation study using a sentinel lymph node surgical algorithm

    Gynecol. Oncol.

    (2016)
  • E. Darai et al.

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

    Gynecol. Oncol.

    (2015)
  • J. How et al.

    Impact of sentinel lymph node mapping on recurrence patterns in endometrial cancer

    Gynecol. Oncol.

    (2017)
  • K. Greven et al.

    Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer

    Gynecol. Oncol.

    (2006)
  • Y. Todo et al.

    Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis

    Lancet

    (2010)
  • A.A. Secord et al.

    A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer

    Gynecol. Oncol.

    (2013)
  • F. Khoury-Collado et al.

    Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes

    Gynecol. Oncol.

    (2011)
  • S. Kumar et al.

    Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer

    Gynecol. Oncol.

    (2014)
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