Co-chief of the Gynecologic Oncology Division at the John Theurer Cancer Center in Hackensack, New Jersey.

The author has reported no financial interest with an entity that would pose a conflict of interest with the subject matter of this article.

Babak Litkouhi, MD, Gynecologic Oncology Division, John Theurer Cancer Center, 92 Second St, Hackensack, NJ 07601. E-mail: 

	Endometrial cancer is the most common gynecologic malignancy, affecting approximately 40,000 Americans annually and resulting in approximately 8000 deaths.

 The majority of patients present at an early stage, when the likelihood of cure with surgery alone is relatively high. In a minority of cases appearing to be clinically confined to the uterus, occult metastatic disease will be found at the time of surgical staging, and this will have a considerable impact on prognosis and survival.

 The status of the regional lymph nodes is acknowledged as being one of the primary determinants of prognosis, and national guidelines, including those of the American College of Obstetricians and Gynecologists and the National Comprehensive Cancer Network, support their removal at the time of surgery. This information is used postoperatively to tailor adjuvant therapy by defining those patients who may benefit from systemic chemotherapy, those who may substitute vaginal brachytherapy for whole pelvic teletherapy, and those who may avoid adjuvant therapy altogether.

 role of lymphadenectomy has not been well established, with two recent randomized trials in fact failing to show a survival benefit.

 Although concerns regarding the methodology of these studies have been raised, it is not surprising that there is no consensus in the gynecologic oncology community as to which patients benefit the most from lymph node dissection.

 Debated are the extent of nodal dissection (lymphadenectomy vs lymph node sampling, removal of pelvic vs pelvic and para-aortic nodes with or without removal of “high” infrarenal nodes) and for whom the procedure is best suited. Groups at low, intermediate, and high risk for metastasis have been identified, with intraoperative frozen section being used to categorize patients at the time of surgery. However, because clinically significant discrepancies in grade and final stage are not infrequent when relying on frozen section,

 some advocate full lymphadenectomy on all patients at the time of surgery.

	Though generally a safe procedure, lymphadenectomy is not without risks. Short- and long-term complications are well recognized and include vascular or nerve injury, deep vein thrombosis, lymphocyst, lymphedema, and lymphangitis. These complications may negatively affect survival and quality of life in the many patients for whom the procedure will ultimately have been of minimal or no benefit.

	Sentinel lymph node (SLN) mapping has become a well-accepted procedure in melanoma and breast cancer. The intention of this procedure is to avoid the morbidity of full-scale lymphadenectomy, while still identifying meaningful metastatic disease. This technique has recently gained acceptance in vulvar cancers as well. More recently, a number of investigators have begun to explore the utility and accuracy of this technique in endometrial cancer.

	Sentinel lymph node mapping has been done with blue dye, usually in conjunction with a radioactive tracer, and more recently with a fluorescent green dye. Cervical, tumoral (via hysteroscopy), and serosal injection techniques have been described, with studies reporting SLN detection rates of 45% to 100%, and false-negative rates of approximately 15%.

 The SLNs are processed by ultrasectioning techniques, aided by immunohistochemistry. Interestingly, up to half of nodal metastases identified in SLN studies were missed by traditional hematoxylin and eosin sectioning and were identified via ultrasectioning only.

 All told, SLN mapping may offer a balance between surgical risks and the risk of missing metastatic disease, may help identify micrometastases as well as isolated metastases in areas typically not dissected in the standard lymphadenectomy, and may be of particular benefit in the low-risk population.

	Although SLN mapping conceivably could solve the endometrial cancer staging dilemma, several important questions remain to be answered. First, the true prognostic and/or therapeutic significance of micrometastases identified using ultrasectioning has not yet been clarified for this disease. Questions remain regarding the best method to detect SLNs, such as the optimal mapping compound (blue dye, radioactive tracer, fluorescent green dye, or a combination), the optimal site for injection (cervix, tumor, serosa), and what patient population the technique is best suited for (low, intermediate, or high risk). Furthermore, not all studies investigating the SLN technique have been done in conjunction with full staging lymphadenectomy, hence limiting our understanding of the true false-negative rate with this procedure.

	Lastly, a significant limitation in our understanding of how to best 

 at-risk patients is our lack of consensus as to how to best treat these patients. Although the benefits of systemic chemotherapy are acknowledged, the role of radiation therapy and how best to incorporate it with chemotherapy (brachytherapy vs volume-directed pelvic teletherapy with or without para-aortic teletherapy) are still widely debated.

	The recent literature suggests that SLN mapping shows promise in the management of endometrial cancer, especially if applied using a rigorous staging and treatment algorithm.

 Investigators studying this technique should be commended for their work. However, prior to SLN mapping gaining widespread acceptability, larger multi-institutional studies incorporating backup lymphadenectomy should be performed, and these data should be evaluated in the greater context of the global management of advanced-stage metastatic endometrial cancer.

			Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010 [published correction appears in CA Cancer J Clin. 2011;61(2):133-134]. 

			Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. 

			Morrow CP, Bundy BN, Kurman RT, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. 

			ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study [published correction appears in Lancet. 2009;373(9677):1764]. 

			Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. 

			Soliman PT, Frumovitz M, Spannuth W, et al. Lymphadenectomy during endometrial cancer staging: practice patterns among gynecologic oncologists. 

			Frumovitz M, Singh DK, Meyer L, et al. Predictors of final histology in patients with endometrial cancer. Gynecol Oncol. 2004;95(3):463-468.

			Van Oostrum NH, Makar AP, Van den Broecke R. Sentinel node procedures in gynecologic cancers: an overview. 

			Khoury-Collado F, Glaser GE, Zivanovic O, et al. Improving sentinel lymph node detection rates in endometrial cancer: how many cases are needed? 

			Ballester M, Dubernard G, Lécuru F, et al. Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO).

			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. 

Articles

Sentinel lymph node mapping shows promise in the management of endometrial cancer, especially if applied using a rigorous staging and treatment algorithm.

Babak Litkouhi, MD

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Sentinel Lymph Node Mapping in Endometrial Cancer