SGO Clinical Practice Statement: The Role of Sentinel Lymph Node Mapping in Endometrial Cancer (SGO, November 2015)

November 2015

Sentinel lymph node mapping has the potential to decrease morbidity and optimize the pathologic assessment of identified nodes in women with endometrial cancer.

Surgical staging of apparent uterine-confined endometrial cancers with pelvic ± aortic lymphadenectomy has traditionally been performed in order to identify and triage patients that might benefit from adjuvant therapies. However, systematic retroperitoneal lymphadenectomy procedures have been associated with increased morbidity including lymphocysts, lymphedema, and varying degrees of both short and long-term neuralgia. Furthermore, two phase III trials failed to demonstrate a survival benefit with pelvic and selective aortic lymphadenectomy in patients with endometrial cancer [1,2]. Sentinel lymph node (SLN) mapping and ultrastaging of sentinel nodes has been proposed by many gynecologic oncologists as a method to potentially reduce surgical staging morbidity while maintaining prognostic information of lymph node status [3,4]. Initial experiences have been reported using blue dyes and radioactive colloid technetium-99 [5]. The widespread availability of the robotic surgery platform and near-infrared imaging with indocyanine green (ICG) has furthered the investigation of SLN mapping. According to a survey of SGO members, 28.6% of respondents performed SLN mapping, 16.7% with the exclusion of pelvic lymphadenectomy, and 54% of institutions performed pathologic ultrastaging of SLN (46th Annual Meeting on Women’s Cancer, March 28-31, 2015, Chicago, IL). A SLN algorithm is now included in the NCCN Guidelines for Endometrial Carcinoma with category-3 evidence [6,7].

The role of SLN mapping is currently being evaluated prospectively in several centers. No prospective phase III trials have reported comparisons of SLN mapping to traditional lymphadenectomy in endometrial cancer. If SLN mapping is performed without completion of standard lymphadenectomy, the expertise of the surgeon and attention to technical detail is critical, especially if findings from surgical staging are used to determine adjuvant therapy. The reported detection rate of SLNs varies greatly across retrospective studies from 70-95% (any detection), approximately 50-60% for bilateral detection with blue dyes, and up to 79% with ICG [5, 8-11]. The SLN algorithm requires that side-specific lymphadenectomy be performed in the case of failed mapping, and that grossly enlarged or suspicious lymph nodes be removed, irrespective of mapping results [6]. The learning curve for the reliable detection of SLN has been estimated 30 cases [12]. Following guidelines from ASCO and ASBS on acceptable proficiency for breast cancer SLN mapping, the metastasis detection rate for SLN should be >80-90% and the false negative rate for normal SLN should be < 5% [13]. Therefore gynecologic oncologists should consider continuing to perform full lymphadenectomy while their individual experience with SLN mapping is accrued (at least 20-30 cases), and possibly until their detection rate for metastasis can be documented within the suggested breast SLN guidelines.

Several SLN mapping techniques have been described and include use of blue dyes (isosulfan blue (ISB), methylene blue, patent blue), indocyanine green (ICG) dye with immunofluorescence detection, and radiolabeled technetium with lymphoscintigraphy. Hysteroscopic, fundal and myometrial injections have been explored, however most recent studies have reported intracervical, submucosal injection of dyes. This appears to be a reproducible technique that adequately maps the pelvic lymph nodes and occasionally lower aortic nodes. There are insufficient data to suggest that the upper aortic lymph nodes (above the inferior mesenteric artery) can be reliably mapped using current cervical injection techniques [6]. Decisions regarding the performance of para-aortic lymphadenectomy should continue to be determined by the tumor histology, intraoperative analysis of the primary tumor, and status of pelvic lymph nodes at surgery.

The SLN algorithm includes examination of multiple deeper level sections of nodes using routine staining and/or keratin immunohistochemical staining (i.e., ultrastaging) [6]. These enhanced techniques of SLN pathologic evaluation may identify low volume metastases and/or keratin-positive occult cells but the prognostic value of these findings remains uncertain [5]. Adjuvant therapies should be considered carefully in relation to the risk profile of the primary tumor. The management of isolated tumor cells (ITC) and micrometastasis remains a pivotal question that requires further study, preferably answered through well-designed phase III clinical trials.

In conclusion, SLN mapping with adherence to a surgical algorithm and pathologic ultrastaging is a reasonable staging strategy that provides information on nodal metastasis and potentially reduces morbidity in patients with apparent uterine confined endometrial cancer. Patients should be counseled that the degree of reduction in morbidity associated with SLN sampling, the false negative rate of SLN mapping, and the clinical significance of low volume metastasis with respect to disease recurrence and decisions regarding adjuvant therapy are still under investigation. Prospective clinical trials designed to assess the clinical impact of SLN mapping in endometrial cancer should be encouraged in cooperative group settings.

References

1. Kitchener H, Swart AM, Qian Q, et al. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet 2009; 373: 125-136.
2. Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J. Natl. Cancer Inst. 2008; 100: 1707-1716.
3. Abu-Rustum NR. Sentinel lymph node mapping for endometrial cancer: a modern approach to surgical staging. J. Natl. Compr. Canc. Netw. 2014; 12: 288-297.
4. Abu-Rustum NR. Update on sentinel node mapping in uterine cancer: 10-year experience at Memorial Sloan-Kettering Cancer Center. J. Obstet. Gynaecol. Res. 2014; 40: 327-334.
5. Ballester M, Dubernard G, Lecuru F, 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; 12: 469-476.
6. Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: Beyond removal of blue nodes. Gynecol. Oncol. 2012; 125: 531-535.
7. Uterine Neoplasms. Version 2.2015: NCCN Clinical Practice Guidelines in Oncology.
8. Jewell EL, Huang JJ, Abu-Rustum NR, 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; 133: 274-277.
9. How J, Gotlieb WH, Press JZ, et al. Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer. Gynecol. Oncol. 2015; 137: 436-443.
10. Tanner EJ, Sinno AK, Stone RL, et al. Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer. Gynecol. Oncol. 2015; 138: 542-547.
11. Smith B, Backes F. The role of sentinel lymph nodes in endometrial and cervical cancer. J. Surg. Oncol. Sep. 9 2015; DOI: 10.1002/jso.24022.
12. Khoury-Collado F, Glaser GE, Zivanovic O, et al. Improving sentinel lymph node detection rates in endometrial cancer: How many cases are needed? Gynecol. Oncol. 2009; 115: 453-455.
13. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J. Clin. Oncol. 2005; 23: 7703-7720.

DISCLAIMER: Clinical Practice Statements are intended to be educational devices that provide information that may assist healthcare providers in caring for patients. This [Clinical Document] is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring or discouraging any particular treatment. Clinical Practice Statements are not intended to supplant the judgment of the health care provider with respect to particular patients or special clinical situations. Clinical decisions in any particular case involve a complex analysis of a patient’s condition and available courses of action with the ultimate determination to be made by the health care provider in light of each individual patient’s circumstances. Therefore, clinical considerations may lead a healthcare provider to appropriately take a course of action that varies from this Practice Statement.