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What should lymphadenectomy offer in early-stageendometrial cancer: lots of variables, little control

D. Scott McMeekin, MD

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The contemporary view of endometrial cancer suggests thatmost women, fortunately, have low-risk disease, with a

low probability of recurrence following hysterectomy. Identi-fying the smaller subset of patients with disease spread at pre-sentation or who may benefit from adjuvant therapy remainsthe challenge. Risk of disease recurrence and survival has beenrelated to simple models evaluating uterine characteristics,nodal status, and use of adjuvant therapy.

Additional data based on patient age, tumor histology, andspecific type of adjuvant therapy may fine-tune risk modelseven further. In 2011, the extent of disease spread, or stage,remains the single most important factor for defining use ofadjuvant therapy and prognosis. Of the methods to assess dis-ease spread, lymph node dissection is the best technique foridentifying the approximately 9% of patients with otherwiseunrecognized disease spread. Compared with patients withnode negative disease, patients with node-positive diseasecarry different prognoses and largely receive different thera-pies. Compared with those patients with unresected/unrecog-nized positive nodes, those node positive patients treated withlymphadenectomy perhaps achieve better result with the sametherapies once use.

The use of lymph node dissection as a routine practice or aselective one is the source of considerable debate and activeresearch and largely relates the marginal benefit that may beachieved in a particular population.

In the late 1990s to the early 2000s, a paradigm based onincreasing use of lymphadenectomy was discussed in the liter-ature. Lymphadenectomy was suggested to be a therapeuticendeavor and could lead to a substitution of vaginal cuffbrachytherapy for pelvic radiation therapy.1-3 Data alsomerged suggesting that nodal status could be used as a ful-rum; node-negative patients would receive surveillance,ode-positive patients would receive adjuvant therapy.4,5

Lymph node status as a single variable, however, probably pro-duces an incomplete picture of disease behavior.

From the Department of Obstetrics and Gynecology, University ofOklahoma, Oklahoma City, OK.

Received Aug. 4, 2011; accepted Sept. 6, 2011.

The author reports no conflict of interest.

Reprints: D. Scott McMeekin, MD, Department of Obstetrics andGynecology, P.O. Box 26901, University of Oklahoma, Oklahoma City,OK 73190. Scott-Mcmeekin@ouhsc.edu.

0002-9378/free© 2011 Mosby, Inc. All rights reserved.doi: 10.1016/j.ajog.2011.09.003

See related article, page 562

Understanding the importance of grade, depth of myome-trial invasion (DOI), and lymphovascular space invasion(LVSI) in predicting recurrence and survival vs nodal status asa single variable has been difficult, and uterine characteristicsmay confound potential advantages of nodal dissection. Datafrom the Gynecologic Oncology Group study 99 demonstratedthat in the setting of stage I-II disease with negative lymphnodes, information on patient age, LVSI, DOI, and tumorgrade could define a population of patients with a 27% risk ofrecurrence treated by surgery alone, including 19% of patientsrecurring at a distant sites.6 In a population based study from

anada, Kwon et al7 suggested that high-risk uterine factorsere more important determinants of survival than nodal sta-

us. Both studies have been criticized for the extent and qualityf the nodal assessment, however.The extent to which the quality of lymph node dissection alters

utcomes is a source of controversy. The number of nodes re-oved (a surrogate of the completeness of dissection) and the

xtent of dissection (pelvic and/or paraaortic) are variables thatay have an impact on outcomes but are seldom controlled. Both

ecent prospective randomized trials evaluating hysterectomyith or without routine pelvic lymphadenectomy were criticized

or the absence of paraaortic nodal dissections.8,9 Both studiesshowed that pelvic lymphadenectomy did not alter survival.

A subsequent retrospective Japanese series suggested that asurvival benefit may be achieved by removing paraaortic nodesin addition to pelvic nodes.10 That trial, however, did not con-rol well for postoperative use of chemotherapy, another vari-ble that may blur the outcomes associated with lymphadenec-omy. The ASTEC (A Study in the Treatment of Endometrialancer) trial was criticized by the fact that 8% of patients on

he nodal dissection arm had no nodal dissection at all, and5% had less than 10 lymph nodes removed.8

Sharma and colleagues11 have evaluated a large populationatabase and suggested that the knowledge of lymph node sta-us changes use of adjuvant therapy in select patient popula-ions. In the Surveillance, Epidemiology, and End ResultsSEER) analysis, a higher lymph node number (�10) was as-ociated with less use of pelvic radiation, perhaps suggestingreater confidence in avoiding pelvic radiation in patients withhorough staging. What factors contribute to a less extensiveesection (patient and physician) and how these may alter out-omes are, again, unknown. The SEER data do not report thextent of pelvic and/or paraaortic dissections.

It is interesting to note that in the SEER analysis by Sharma andolleagues,11 lymphadenectomy did not alter use of adjuvant pel-

vic radiation in low- or high-risk patients but was associated witha change in the type of radiation therapy used in intermediate-risk

patients (more common use of vaginal brachytherapy). Perhaps

DECEMBER 2011 American Journal of Obstetrics & Gynecology 509

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Editorials www.AJOG.org

striking, however, was the finding that regardless of age group(�60 or �60 years old), patients who underwent a lymph nodedissection with stage IB, Gr2-3 disease received any radiation(pelvic or vaginal) more commonly compared with those whodid not undergo lymph node dissection (25% vs 20%). This in-teresting finding from the data suggests that we may be overtreat-ing patients or that lymphadenectomy is not altering our decisionmaking in terms of using any radiation or not.

IsthestudybySharmaandcolleagues11thenanotherindictmentofymphadenectomy? It would seem the authors’ discussion that “op-imaladjuvanttreatmentformostwomenwithendometrialcancerisnknown”is thecruxofthe lymphadenectomydebate. Ifpatientsaret low risk for recurrence or do not benefit from adjuvant therapy,hen there is probably a limited role for lymphadenectomy in thisopulationaswell. Inpatientsathighriskforrecurrence,regardlessofodal status, does the effect of adjuvant therapy blunt benefit from

ymphadenectomy?Today lymphadenectomy is the discriminating test for risk,

ut tomorrow tissue or serum biomarkers may be better tools.emonstrating the value and effect of lymph node dissection

ontinues to be difficult because of the multiple variables thatre related to use of adjuvant therapy, recurrence, and survival.any of us think that lymphadenectomy can help at least some

ubset of our patients and believe that the information from therocedure fine-tunes our use of therapy. The data Sharma andolleagues11 support the belief that a lymph node dissection

alters the use of postoperative radiation but perhaps not asmuch as we would like to think. Given the variety of variablesthat may confound the single question of what does a nodaldissection offer, trials that control for the extent of nodal dis-

section and the use of postoperative therapy are essential. f

510 American Journal of Obstetrics & Gynecology DECEMBER 2011

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