Sentinel Lymph Node Excision Has Value in Endometrial Cancer

Sumer K. Wallace, MD

Assistant Professor

Department of Obstetrics and Gynecology

Division of Gynecologic Oncology

University of Wisconsin School of Medicine and Public Health at Madison

With an estimated 63,230 new cases diagnosed in 2018, endometrial carcinoma is the most common gynecologic cancer in the United States.¹ Standard treatment involves minimally invasive surgery including pelvic lymph node evaluation.² Traditionally, pelvic lymph node evaluation consists of total lymphadenectomy, which carries a 23% risk of lymphedema of the lower extremity.³ Although the therapeutic utility of lymphadenectomy is uncertain, it continues to provide information for staging and helps to guide postoperative adjuvant treatment. Excision of sentinel lymph nodes in the pelvis has emerged as a surgical method to reduce morbidity and provide information essential to understanding disease progression and management.

Sentinel lymph node excision has been established as standard of care for cancer of many disease sites. For example, it is used to guide management in melanoma, breast cancer, and vulvar cancer. In 2014, the National Comprehensive Cancer Network (NCCN) added sentinel lymph node excision to its guidelines for the management of endometrial cancer.²

Multiple methods for sentinel lymph node detection for endometrial cancer have been studied and described. Injection of the cervix with indocyanine green dye and identification of the sentinel lymph nodes with a nearinfrared— capable camera has emerged as the superior technique.⁴ Sentinel lymph nodes are often identified in the pelvis; however, they can be presacral or para-aortic in location as well. It is important to note that more than 1 sentinel lymph node can be present. Additionally, the NCCN algorithm for sentinel lymph node excision for endometrial cancer includes complete lymphadenectomy if a sentinel lymph node cannot be identified on any given side. In addition, any enlarged lymph nodes should be excised regardless of sentinel lymph node identification.²

Currently, sentinel lymph node excision for endometrial cancer is most widely accepted for low-risk endometrial cancer. This includes uterine-confined, grade 1 or 2 endometrial cancer.² Lymph node mapping can identify the sentinel lymph node in a high percentage of cases and has high sensitivity for nodal positivity and a low false-negative rate. In the FIRES trial, a multicenter, prospective, cohort study of patients undergoing robotic hysterectomy for clinical stage I endometrial cancer, lymph node mapping achieved 97.2% node-positive sensitivity with a negative predictive value of 99.6%.⁵ Meta-analyses have confirmed identification of sentinel lymph nodes to be >80%, sensitivity for detection of positive lymph nodes to be 95% to 97%, and the negative predictive value to be >97%.^4,6,7 Given the increased ability to detect lymph node positivity for metastatic disease, likely secondary to pathologic ultrastaging of sentinel lymph nodes, women who underwent sentinel lymph node excision for endometrial cancer were more likely to receive adjuvant treatment.^6,7

There is less agreement on the value of performing sentinel lymph node excision for high-risk endometrial cancer. Results of published studies have shown that extending this surgical approach to patients with grade 3 endometrial cancer or high-risk histologies may be reasonable and feasible. For example, Soliman et al performed a prospective validation study of patients with grade 3, carcinosarcoma, serous, or clear cell endometrial cancer. This study reported an 89.0% sentinel lymph node detection rate, 95.0% sensitivity, a 5.0% false-negative rate, and a 98.6% negative predictive value.⁸ Similarly, Touhami et al performed a retrospective analysis of women who underwent surgery, including sentinel lymph node evaluation, for grade 3, carcinosarcoma, serous, clear cell, and undifferentiated endometrial cancers. They reported an 89.8% sentinel lymph node mapping rate, 95.8% sensitivity, and a 98.2% negative predictive value.⁹ Although these data are promising and some have begun implementing sentinel lymph node excision for patients with both lowand high-risk endometrial cancers, this method has not been universally adopted, and further long-term data are anticipated.

As targeted treatment strategies and patient satisfaction become more essential to healthcare, surgical techniques must evolve to meet expectations and reduce postoperative sequelae. Fewer invasive procedures, such as laparoscopy and minimally invasive surgery, are the standard approach for many types of pathology, including endometrial cancer. The addition of sentinel lymph node excision, in place of total lymphadenectomy, has provided a less morbid procedure for our patients while offering the same important information to guide care.

References

1. American Cancer Society. Key statistics for endometrial cancer. American Cancer Society website. www.cancer.org /cancer/endometrial-cancer/about/key-statistics.html. Updated January 9, 2019. Accessed December 2, 2018.
2. Koh WJ, Abu-Rustum NR, Bean S, et al. Uterine neoplasms, version 1.2018, nccn clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16(2):170-199. doi: 10.6004/jnccn.2018.0006.
3. Yost KJ, Cheville AL, Al-Hilli MM, et al. Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life. Obstet Gynecol. 2014;124(2 Pt 1): 307-315. doi: 10.1097/AOG.0000000000000372.
4. How JA, O’Farrell P, Amajoud Z, et al. Sentinel lymph node mapping in endometrial cancer: a systematic review and meta-analysis. Minerva Ginecol. 2018;70(2):194-214. doi: 10.23736/S0026-4784.17.04179-X.
5. Rossi EC, Kowalski LD, Scalici J, 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;18(3):384-392. doi: 10.1016/S1470-2045(17)30068-2.
6. Bodurtha Smith AJ, Fader AN, Tanner EJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(5):459-476. doi: 10.1016/j.ajog.2016.11.1033.
7. Cormier B, Rozenholc AT, Gotlieb W, Plante M, Giede C; Communities of Practice (CoP) Group of Society of Gynecologic Oncology of Canada (GOC). Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research. Gynecol Oncol. 2015;138(2):478-485. doi: 10.1016/j.ygyno.2015.05.039.
8. Soliman PT, Westin SN, Dioun S, et al. A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer. Gynecol Oncol. 2017;146(2):234-239. doi: 10.1016/j.ygyno.2017.05.016.
9. Touhami O, Gregoire J, Renaud MC, Sebastianelli A, Plante M. Performance of sentinel lymph node (SLN) mapping in high-risk endometrial cancer. Gynecol Oncol. 2017;147(3):549-553. doi: 10.1016/j.ygyno.2017.09.014.