lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer
TRANSCRIPT
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56tion andhelps to guide adjuvant treatmentplanning.6,7 As the use of lymphadenec-tomyincreased,dataemergedthat thepro-cedure may provide a therapeutic benefitin and of itself; those patients who under-went a more extensive dissection had im-proved survival.8-10 However, 2 recentrandomized trials cast doubt on the role ofnodal dissection. Both of these studies
prints: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics andnecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave.,hth Flr., New York, NY. 10032. [email protected].
2-9378/free 2011 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2011.09.001
For Editors Commentary, see Table of Contentsoorer prognosis. Age, stage, tumorde, histologic type, depth of myo-trial invasion, and metastasis to the
landmark surgicopathpatients with clinicalthis report the inves
m theDepartment ofRadiationOncology (Drs Sharma,Deutsch, andCynecologicOncology,Department ofObstetrics andGynecology (Drs LWright,MsQiao, andMsSun),College of Physicians and Surgeons, and
mprehensiveCancerCenter (DrsDeutsch, Lewin, Burke,Chao,Herzog,lumbiaUniversity,NewYork,NY.
ceived March 15, 2011; revised May 19, 2011; accepted Sept. 6, 2011.
s study was supported by the Milstein Family Research Fund.See related editorial, page 509
2.e1 American Journal of Obstetrics& Gynecology DECEMBER 2011ogy study of 621ge I tumors. Intors noted that
further acknowledged in 1988 when asurgical staging system that includedpathologic assessment of the regionalnodes was adopted.5
With the recognition of the importanceof the status of the regional lymphatics,lymphadenectomy was incorporated intothe primary surgical management ofwomen with endometrial cancer.6-9
Proponents of the procedure argue that itprovides important prognostic informa-
) and theDivisionn, Burke,Herzog,rbert IrvingWright),nosed at an early stage and have aorable outcome, a number of clini-pathologic risk factors predispose to
dometrial cancer. The GynecologicOncology Group (GOG) demonstratedthe importance of nodal metastasis in a
was 58% and decreased to 41% forwomen with paraaortic metastases.4NCOLOGY
ymphadenectomy indiation treatment foaru Sharma, MD; Israel Deutsch, MD; Shming Sun, MS; Clifford K. Chao, MD; T
JECTIVE: We analyzed the effect of lymphadeuvant radiation treatment for women with scer.
UDY DESIGN: Women with stage I-II endometrated between 1988 and 2006 and recorded iniology, and End Results database were identphadenectomy (LND) on receipt of externalchytherapy stratified was examined.
SULTS: We identified 58,776 women includinnt LND (44.3%). Among women younger than
this article as: Sharma C, Deutsch I, Lewin SN, et atet Gynecol 2011;205:562.e1-9.
ndometrial cancer is the mostcommon gynecologic malignancy.
the United States, it is estimated that,470 women will be diagnosed withendometrial cancer in 2010 and
t 7950 will die from the disease.1 Al-uences the utilizatioendometrial canceryn N. Lewin, MD; William M. Burke, MDas J. Herzog, MD; Jason D. Wright, MD
tomy on the use ofe I-II endometrial
adenocarcinomasSurveillance, Epi-. The influence ofam radiation and
6,043 who under-years of age with
stage IA (grades 1, 2, anradiation. Patients with s2) tumors who underwendergo external beam radtherapy (P .05 for all)influenced the receipt of
CONCLUSION: Women wto receive whole pelvic r
Key words: endometriadissection, radiation, ute
ymphadenectomy influences the utilization of adjuva
ional lymph nodes are all estab-hed prognostic factors.2-4
Metastasis to the pelvic and paraaorticph nodes is widely recognized as thefouof adjuvant
aming Qiao, MS;
) tumors, LND had no impact on the use ofe IB (grade 2 or 3) and stage IC (grade 1 ormph node dissection were less likely to un-n andmore likely to receive vaginal brachy-rthermore, the extent of lymphadenectomyiation.
undergo lymphadenectomy are less likelytherapy.
ncer, lymphadenectomy, lymph nodecancer
adiation treatment for endometrial cancer. Am J
ional lymph nodes were the mostmmon site of extrauterine disease andt the frequency of nodal dissemina-n correlated with tumor grade andpth of myometrial invasion. Fivear recurrence-free survival for pa-flrarhom
nectag
ioidtheifiedbend that lymphadenectomy had no ef-
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ad
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altwocantiopaionaptharad
potheentredo
MDatutEnlizregmaSEdisSEweexerev
adtreclupasis(1,lec198
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tic
www.AJOG.org Oncology Researcht on survival and that theprocedurewasociatedwith a small, but statistically sig-cant, increase in morbidity.11,12
Given the conflicting data on lymph-
TABLE 1Clinical and demographic characteris
Characteristic No lymphadenectomy
32,733 (55.7)..........................................................................................................................
Age, y.................................................................................................................
60 13,718 (41.9).................................................................................................................
60 19,015 (58.1)..........................................................................................................................
Race.................................................................................................................
White 29,371 (89.7).................................................................................................................
Black 1243 (3.8).................................................................................................................
Other 2007 (6.1).................................................................................................................
Unknown 112 (0.3)..........................................................................................................................
Year of diagnosis.................................................................................................................
1988-1994 8572 (26.2).................................................................................................................
1995-2000 10,032 (30.7).................................................................................................................
2001-2006 14,129 (43.2)..........................................................................................................................
SEER registry.................................................................................................................
West 16,530 (50.5).................................................................................................................
Central 9352 (28.6).................................................................................................................
East 6851 (20.9)..........................................................................................................................
Marital status.................................................................................................................
Married 18,125 (55.4).................................................................................................................
Single 13,540 (41.4).................................................................................................................
Unknown 1068 (3.3)..........................................................................................................................
Tumor grade.................................................................................................................
1 19,347 (59.1).................................................................................................................
2 9609 (29.4).................................................................................................................
3 2187 (6.7).................................................................................................................
Unknown 1590 (4.9)..........................................................................................................................
Radiation.................................................................................................................
External beam 3727 (11.4).................................................................................................................
Brachytherapy 875 (2.7).................................................................................................................
Other 165 (0.5).................................................................................................................
None 27,966 (85.4)..........................................................................................................................
Stage.................................................................................................................
IA 12,129 (37.1).................................................................................................................
IB 16,127 (49.3).................................................................................................................
IC 3447 (10.5).................................................................................................................
IIA 570 (1.7).................................................................................................................
IIB 460 (1.4)..........................................................................................................................
SEER, Surveillance, Epidemiology, and End Results.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obenectomy, performance of the proce-cedjuvre is now actively debated.13 Althoughappears that lymphadenectomy doest directly influence survival, the pro-
s of the cohort
Lymphadenectomy P value
26,043 (44.3)...........................................................................................................
.16...........................................................................................................
10,766 (41.3)...........................................................................................................
15,277 (58.7)...........................................................................................................
.0001...........................................................................................................
22,707 (87.2)...........................................................................................................
1251 (4.8)...........................................................................................................
1980 (7.6)...........................................................................................................
105 (0.4)...........................................................................................................
.0001...........................................................................................................
3451 (13.3)...........................................................................................................
6631 (25.5)...........................................................................................................
15,961 (61.3)...........................................................................................................
.0001...........................................................................................................
14,134 (54.3)...........................................................................................................
6199 (23.8)...........................................................................................................
5710 (21.9)...........................................................................................................
.47...........................................................................................................
14,387 (55.2)...........................................................................................................
10,848 (41.7)...........................................................................................................
808 (3.1)...........................................................................................................
.0001...........................................................................................................
9695 (37.2)...........................................................................................................
10,124 (38.9)...........................................................................................................
4880 (18.7)...........................................................................................................
1344 (5.2)...........................................................................................................
.0001...........................................................................................................
4598 (17.7)...........................................................................................................
1954 (7.5)...........................................................................................................
222 (0.9)...........................................................................................................
19,269 (74.0)...........................................................................................................
.0001...........................................................................................................
6042 (23.2)...........................................................................................................
13,006 (49.9)...........................................................................................................
4898 (18.8)...........................................................................................................
1008 (3.9)...........................................................................................................
1089 (4.2)...........................................................................................................
Gynecol 2011.ure may be important in guiding ad-ant treatment planning. Although CA
DECEMBER 2011 Americanall institutional studies have sug-ted that nodal dissection effects theocation of adjuvant treatment, thepulation-based effect of lymphade-ctomy on influencing patterns of careains unknown.6,8,14
Even if lymphadenectomy does noter survival, the procedure may berthwhile in subsets of patients if itspare women unnecessary addi-
nal treatment. Surgically stagedtients may avoid adjuvant radiat-altogether or opt for brachyther-
y, which is associated with survivalt is comparable with whole pelviciation.15-17
The goal of our study was to perform apulation-based analysis to determineeffect of lymphadenectomy on influ-
cing the use of adjuvant radiationatment for women with stage I-II en-metrial cancer.
ATERIALS AND METHODSta from the National Cancer Insti-es Surveillance, Epidemiology, andd Results (SEER) database was uti-ed. SEER is a population-based tumoristry that captures data on approxi-tely 26% of the US population.18
ER comprises several geographicallytinct tumor registries. Data fromER17 registries was utilized.19 All datare publicly available, deidentified, andmpt from institutional review boardiew.Women with stage I-II endometrioidenocarcinomas of the uterine corpusated between 1988 and 2006 were in-ded in the analysis. The clinical andthologic date including age at diagno-(60 or60 years old), tumor grade2, or 3), and marital status were col-ted. Theyearofdiagnosiswasclassifiedas8-1994, 1995-2000, or 2001-2006.Patients were categorized based on thegraphic area of residence at the timediagnosis: central (Detroit, MI; Iowa;ntucky; Louisiana; Utah), easternonnecticut; New Jersey; Atlanta, GA;ralGeorgia), andwestern (Alaska;Cal-rnia; Hawaii; Los Angeles, CA; Newxico; San Francisco, CA; San Jose,duitno
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stet; Seattle, WA) United States.
Journal of Obstetrics& Gynecology 562.e2
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terlecnaweati
mogoeffonanwhpa
f ra ear
Ex Vag
Lydin
Lymdissn (%
......... .........
7 52......... .........
1 15......... .........
2 15......... .........
2 13.......... ..........
Research Oncology www.AJOG.org
56Use of adjuvant radiation therapy (ex-nal beam or brachytherapy) was col-ted. Patients who received both exter-l beam and vaginal brachytherapyre included in the external beam radi-on group.Patients who had any lymph nodes re-ved were classified as having under-ne lymphadenectomy. To assess theect of the extent of lymphadenectomythe use of adjuvant therapy, a secondalysis was performed among womeno underwent lymphadenectomy com-
TABLE 2Effect of lymphadenectomy on use o
Variable TotalLymphnodes
Nolymphnodes
IA................................................................................................................
All IA 9861 3316 6545................................................................................................................
Grade 1 6596 1849 4747................................................................................................................
Grade 2 2231 978 1253................................................................................................................
Grade 3 414 279 135.........................................................................................................................
IB................................................................................................................
All IB 11,606 5415 6191................................................................................................................
Grade 1 6064 2179 3885................................................................................................................
Grade 2 3842 2084 1758................................................................................................................
Grade 3 1177 889 288.........................................................................................................................
IC................................................................................................................
All IC 1691 1107 584................................................................................................................
Grade 1 578 320 258................................................................................................................
Grade 2 650 438 212................................................................................................................
Grade 3 388 297 91.........................................................................................................................
IIA................................................................................................................
All IIA 666 428 238................................................................................................................
Grade 1 290 162 128................................................................................................................
Grade 2 258 168 90................................................................................................................
Grade 3 79 66 13.........................................................................................................................
IIB................................................................................................................
All IIB 660 500 160................................................................................................................
Grade 1 203 136 67................................................................................................................
Grade 2 282 212 70................................................................................................................
Grade 3 136 120 16.........................................................................................................................
Total number of patients for each substage includes patients with
Sharma. Lymphadenectomy for endometrial cancer. Am J Obring those with 1-9 nodes removedwith an
2.e3 American Journal of Obstetrics& Gynecologyse who had 10 or more nodes re-ved.20 Staging information was deter-ned for each patient using the extent ofease codes and was based on the 1988ernational Federation of Gynecologyd Obstetrics (FIGO) staging system.linical and demographic characteris-
s of the cohort were compared basedthe performance of lymphadenec-y and compared using the 2 test.
e of external beam and vaginal brachy-rapy was then compared based on therformance of lymphadenectomy. These
diation in women younger than 60 y
ternal beam radiation
mph nodessection,(%)
No lymph nodedissection,n (%) P value
.........................................................................................................................
5 (2.3) 68 (1.0) .0001.........................................................................................................................
7 (0.9) 31 (0.7) .25.........................................................................................................................
7 (2.8) 23 (1.8) .14.........................................................................................................................
7 (9.7) 10 (7.4) .45........................................................................................................................
.........................................................................................................................
4 (10.6) 457 (7.4) .0001.........................................................................................................................
9 (4.1) 135 (3.5) .23.........................................................................................................................
3 (8.9) 200 (11.4) .008.........................................................................................................................
7 (30.0) 105 (36.5) .04........................................................................................................................
.........................................................................................................................
9 (42.4) 311 (53.3) .0001.........................................................................................................................
7 (27.2) 116 (45.0) .0001.........................................................................................................................
7 (40.4) 129 (60.9) .0001.........................................................................................................................
2 (64.7) 61 (67.0) .68........................................................................................................................
.........................................................................................................................
3 (35.8) 99 (41.6) .14.........................................................................................................................
2 (25.9) 43 (33.6) .15.........................................................................................................................
8 (40.5) 45 (50.0) .14.........................................................................................................................
2 (48.5) 9 (69.2) .17........................................................................................................................
.........................................................................................................................
2 (56.4) 103 (64.4) .07.........................................................................................................................
2 (45.6) 38 (56.7) .14.........................................................................................................................
1 (57.1) 48 (68.6) .09.........................................................................................................................
9 (65.8) 13 (81.3) .22........................................................................................................................
nown tumor grade.
Gynecol 2011.alyseswere stratifiedby stage, grade, and dis
DECEMBER 2011at diagnosis. P .05 was consideredtistically significant. All analyses wererformed with SAS version 9.2 (SAS In-ute Inc, Cary, NC).
SULTStotal of 58,776 women including,043 who underwent lymph nodepling (44.3%) and 32,733 who did
t undergo lymphadenectomy (55.7%)re identified. The clinical and demo-phic characteristics of the cohort are
s of age
inal brachytherapy
ph nodeection,)
No lymph nodedissection,n (%) P value
............................................................................................................
(1.6) 53 (0.8) .0005............................................................................................................
(0.8) 29 (0.6) .37............................................................................................................
(1.5) 15 (1.2) .49............................................................................................................
(4.7) 2 (1.5) .10...........................................................................................................
............................................................................................................
(7.3) 217 (3.5) .0001............................................................................................................
(3.6) 95 (2.5) .01............................................................................................................
(7.9) 100 (5.7) .008............................................................................................................
(13.8) 13 (4.5) .0001...........................................................................................................
............................................................................................................
(11.7) 24 (4.1) .0001............................................................................................................
(13.1) 16 (6.2) .006............................................................................................................
(10.5) 4 (1.9) .0001............................................................................................................
(7.1) 3 (3.3) .19...........................................................................................................
............................................................................................................
(19.4) 20 (8.4) .0002............................................................................................................
(19.1) 13 (10.2) .03............................................................................................................
(19.6) 6 (6.7) .006............................................................................................................
(13.6) 0 () .16...........................................................................................................
............................................................................................................
(10.6) 13 (8.1) .36............................................................................................................
(15.4) 4 (6.0) .05............................................................................................................
(11.3) 9 (12.9) .73............................................................................................................
(5.8) 0 () .32...........................................................................................................thomomidisIntanC
ticontomUsthepe
agestapestit
REA26samnowegra
......... .........
57 397......... .........
8 78......... .........
18 164......... .........
26 123.......... ..........
......... .........
46 130......... .........
8 42......... .........
17 46......... .........
19 21.......... ..........
......... .........
15 83......... .........
4 31......... .........
6 33......... .........
3 9.......... ..........
......... .........
28 53......... .........
6 21......... .........
12 24......... .........
7 7.......... ..........
unk
stetplayed in Table 1. Patients who un-
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tiePa(grstalikthe.05gra(grtomvagno
nethewhstrremyoIB(grunnelikanbraun(1-plene1-9atiha.00theamold
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ag
A,straof avagundsecSha
www.AJOG.org Oncology Researchrwent lymphadenectomy were moreennonwhite,werediagnosedfrom20012006, and resided in the westernUnitedtes (P .0001 for all). Women withh-grade tumors andpatientswithmorevanced-stage disease were also moreely to undergo lymphadenectomy (P01 for both).Table 2 displays the use of radiationternal beam and vaginal brachyther-y) in women younger than 60 years ofstratified by stage and grade. Amongwomen with stage IA tumors
ades 1, 2, and 3), lymph node dis-tion had no impact on the use ofiation. Patients with stage IB tu-rs (grade 2 or 3) who underwentph node dissection were less likelyundergo external beam radiationd were more likely to receive vaginal
FIGUREUse of external beam radiation and v
Use of external beam radiation in women youngetified by performance of lymphadenectomy. B, Uge or older. C, Use of vaginal brachytherapy ininal brachytherapy in women 60 years of ageerwent lymphadenectomy, dashed red line reption.rma. Lymphadenectomy for endometrial cancer. Am J Obsteachytherapy (Figure). For example, lymong the women with stage IB gradeumors, external beam radiation wasministered to 30.0% of those whoderwent lymphadenectomy com-red with 36.5% of those who did notdergo lymphadenectomy (P .04),ereas brachytherapy was given to.8% of those who underwent nodalsection and to 4.5% of those who didt (P .0001).Similar trends were noted for womenth stage IC (grade 1 and 2) tumors.ong those with stage IC grade 2 neo-sms, 40.4% of women who had aph node dissection received external
am radiotherapy vs 60.9% of thoseo did not (P .0001). In addition,.5% of those who underwent lymphde dissection received vaginal brachy-rapy compared with 1.9% with no
inal brachytherapy
an 60 years of age with stage IB or IC tumorsof external beam radiation in women 60 yearsen younger than 60 years of age. D, Use oflder. Solid blue line represents women whonts women who did not undergo nodal dis-
ecol 2011.ph node dissection (P .0001).proate
DECEMBER 2011 AmericanThese findings were similar for pa-nts 60 years of age or older (Table 3).tients with stage IA (grade 3), stage IBade 2), stage IC (grades 1 and 2), andge IIA (grade 2) tumors were lessely to receive pelvic radiotherapy ify underwent lymphadenectomy (P for all). Patients with stage IB (alldes), stage IC (all grades), and stage IIAade 2) who underwent lymphadenec-y were more likely to receive adjuvantinal brachytherapy than those who didt undergo lymphadenectomy.The influence of extent of lymphade-ctomy on the use of radiation wasn examined (Tables 4 and 5). Patientso underwent lymphadenectomy wereatified based on the number of nodesoved (1-9 vs 10 nodes). Patients
unger than 60 years of age with stage(grades 2 and 3), IC (all grades), IIAade 1), and IIB (grade 2) tumors whoderwent a more extensive lymphade-ctomy (10 or more nodes) were lessely to receive external beam radiationd more likely to receive vaginalchytherapy than those patients whoderwent less extensive nodal sampling9 nodes) (P .05 for all). For exam-, among women with stage IC grade 2oplasms, 54.8% of women who hadnodes removed received pelvic radi-
on comparedwith 31.0%of thosewhod 10 or more nodes removed (P 01). Similar trends were noted whenextent of lymphadenectomy was ex-ined in patients 60 years of age orer.
MMENTe role of lymphadenectomy in endo-trial cancer is rapidly evolving. Ran-mized trials of lymphadenectomyve failed to show a survival advantagethe procedure and have not convinc-ly demonstrated that lymphadenec-y influences adjuvant treatmentnning.11,12 Our population-basedalysis of patients treated across theited States clearly demonstrates thatperformance of lymphadenectomy
ects the allocation of adjuvant treat-nt. The effects appear to be the mostnounced for women with intermedi-am3 tadunpaunwh13disno
wiAmplalymbewh10nothe
r thsewomor orese
t Gynrisk tumors and suggest that those
Journal of Obstetrics& Gynecology 562.e4
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woarerad
oftotremetiecorwivivgra
f ra ol
Ex Vag
Lydin
Lymdissn (%
......... .........
1 52......... .........
6......... .........
20......... .........
19.......... ..........
Research Oncology www.AJOG.org
56menwhoundergo lymphadenectomyless likely to receive external beamiation.The difficulty in extrapolating the rolelymphadenectomy is due in large partthe fact that the optimal adjuvantatment for most women with endo-trial cancer is unknown. Among pa-nts with tumors confined to the uterinepus, radiation improves local controlthout having an impact on overall sur-al.2,21-23 Those patients with high-
TABLE 3Effect of lymphadenectomy on use o
Variable TotalLymphnodes
Nolymphnodes
IA................................................................................................................
All IA 8310 2726 5584................................................................................................................
Grade 1 4860 1196 3664................................................................................................................
Grade 2 2225 912 1313................................................................................................................
Grade 3 727 454 273.........................................................................................................................
IB................................................................................................................
All IB 17,527 7591 9936................................................................................................................
Grade 1 7916 2572 5344................................................................................................................
Grade 2 6628 3188 3440................................................................................................................
Grade 3 2242 1485 757.........................................................................................................................
IC................................................................................................................
All IC 6654 3791 2863................................................................................................................
Grade 1 2029 990 1039................................................................................................................
Grade 2 2895 1659 1236................................................................................................................
Grade 3 1452 981 471.........................................................................................................................
IIA................................................................................................................
All IIA 912 580 332................................................................................................................
Grade 1 285 161 124................................................................................................................
Grade 2 367 242 125................................................................................................................
Grade 3 210 140 70.........................................................................................................................
IIB................................................................................................................
All IIB 889 315 151................................................................................................................
Grade 1 221 130 91................................................................................................................
Grade 2 355 243 112................................................................................................................
Grade 3 242 169 73.........................................................................................................................
Total number of patients for each substage includes patients with
Sharma. Lymphadenectomy for endometrial cancer. Am J Obde, deeply invasive tumors, so-called wo
2.e5 American Journal of Obstetrics& Gynecologyh intermediate risk, appear toderive thest benefit from radiation.23
Evidence-based guidelines for theatment of women with corpus-con-eddisease endorse a variety of possibleatments from observation to radia-n in combination with chemother-y.24 Among women with nodal dis-e, controversy also exists with regardoptimal management. Although che-therapy has been shown to be supe-r to radiation, a substantial number of
diation in women 60 years of age or
ternal beam radiation
mph nodessection,(%)
No lymph nodedissection,n (%) P value
.........................................................................................................................
02 (3.7) 141 (2.5) .002.........................................................................................................................
25 (2.1) 43 (1.2) .02.........................................................................................................................
36 (4.0) 52 (4.0) .99.........................................................................................................................
32 (7.1) 35 (12.8) .009........................................................................................................................
.........................................................................................................................
90 (11.7) 857 (8.6) .0001.........................................................................................................................
20 (4.7) 187 (3.5) .01.........................................................................................................................
94 (9.2) 392 (11.4) .004.........................................................................................................................
29 (28.9) 237 (31.3) .24........................................................................................................................
.........................................................................................................................
51 (40.9) 1409 (49.2) .0001.........................................................................................................................
90 (29.3) 461 (44.4) .0001.........................................................................................................................
93 (41.8) 646 (52.3) .0001.........................................................................................................................
15 (52.5) 254 (53.9) .61........................................................................................................................
.........................................................................................................................
87 (32.2) 131 (39.5) .03.........................................................................................................................
35 (21.7) 36 (29.0) .16.........................................................................................................................
76 (31.4) 52 (41.6) .05.........................................................................................................................
70 (50.0) 36 (51.4) .85........................................................................................................................
.........................................................................................................................
15 (53.5) 151 (50.3) .37.........................................................................................................................
68 (52.3) 50 (55.0) .70.........................................................................................................................
20 (49.4) 63 (56.3) .23.........................................................................................................................
97 (57.4) 29 (39.7) .01........................................................................................................................
nown tumor grade.
Gynecol 2011.men in the United States are treated cat
DECEMBER 2011th a combination of chemotherapyd radiation.24-26
Given the uncertain role of radiation inmenwithcancer confined to theuterus,most important rationale for pelvic ra-tion in womenwith unstaged endome-l cancer is for the treatment of occultdal disease.27 Although it is widely hy-thesized that lymphadenectomy influ-ces adjuvant treatment planning, thererelatively few data describing how
dal sampling has an impact on the allo-
der
inal brachytherapy
ph nodeection,)
No lymph nodedissection,n (%) P value
............................................................................................................
(1.9) 67 (1.2) .01............................................................................................................
(0.5) 31 (0.9) .23............................................................................................................
(2.2) 19 (1.5) .19............................................................................................................
(4.2) 13 (4.8) .71...........................................................................................................
............................................................................................................
(7.6) 337 (3.4) .0001............................................................................................................
(3.5) 127 (2.4) .006............................................................................................................
(7.8) 157 (4.6) .0001............................................................................................................
(12.3) 32 (4.2) .0001...........................................................................................................
............................................................................................................
(11.2) 92 (3.2) .0001............................................................................................................
(10.4) 37 (3.6) .0001............................................................................................................
(11.1) 36 (2.9) .0001............................................................................................................
(9.2) 13 (2.8) .0001...........................................................................................................
............................................................................................................
(20.2) 37 (11.1) .0005............................................................................................................
(21.1) 18 (14.5) .15............................................................................................................
(22.7) 13 (10.4) .004............................................................................................................
(10.7) 5 (7.1) .41...........................................................................................................
............................................................................................................
(11.7) 15 (5.0) .001............................................................................................................
(13.1) 6 (6.6) .12............................................................................................................
(11.1) 6 (5.4) .08............................................................................................................
(10.7) 1 (1.4) .01...........................................................................................................higmo
trefintretioapeastomorio
wian
wothediatrianopoenareno
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8 578......... .........
1 89......... .........
2 250......... .........
4 183.......... ..........
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www.AJOG.org Oncology Researchined the effect of increased use of surgi-staging in women with endometrialcer over a 12 year period. The authorsted that theuseofwholepelvic radiationcreased from 16% to 9%. In an evalua-n of women with all stages of endome-l cancer, it was noted that unstaged pa-nts were twice as likely to receive somem of adjuvant radiation as those whoderwent lymph node evaluation.7
Our findings suggest that patientswithge I-II endometrial cancer who un-rgo lymphadenectomy are less likely
TABLE 4Effect of extent of lymphadenectomyin women younger than 60 years of a
Variable Total
1-9lymphnodes
>10lymphnodes
A................................................................................................................
All IA 2998 1351 1647................................................................................................................
Grade 1 1682 806 876................................................................................................................
Grade 2 876 375 501................................................................................................................
Grade 3 242 95 147.........................................................................................................................
IB................................................................................................................
All IB 4947 2101 2846................................................................................................................
Grade 1 2008 931 1077................................................................................................................
Grade 2 1894 781 1113................................................................................................................
Grade 3 801 303 498.........................................................................................................................
IC................................................................................................................
All IC 1016 393 623................................................................................................................
Grade 1 297 124 173................................................................................................................
Grade 2 402 157 245................................................................................................................
Grade 3 268 99 169.........................................................................................................................
IIA................................................................................................................
All IIA 401 131 270................................................................................................................
Grade 1 149 51 98................................................................................................................
Grade 2 161 53 108................................................................................................................
Grade 3 59 18 41.........................................................................................................................
IIB................................................................................................................
All IIB 465 145 320................................................................................................................
Grade 1 130 37 93................................................................................................................
Grade 2 196 66 130................................................................................................................
Grade 3 108 32 76.........................................................................................................................
Total number of patients for each substage includes patients with
Sharma. Lymphadenectomy for endometrial cancer. Am J Obreceive external pelvic radiotherapy wad more likely to undergo treatmentth vaginal brachytherapy. These find-s are most pronounced for patientsth intermediate risk (stage IB grades 2d 3 and IC grades 1 and 2) tumors.Among women without nodal metasta-, theprimary rationale for radiation is tovent locoregional recurrence.28,29 A re-t randomized trial of women with ap-rent stage I-IIA endometrial cancerst-Operative Radiation Therapy fordometrial Carcinoma [PORTEC]-2)monstrated that vaginal brachytherapy
-9 vs >10 nodes) on use of radiationwho underwent nodal evaluation
External beam radiation
1-9 nodes,n (%)
>10 nodes,n (%) P value
.........................................................................................................................
30 (2.2) 33 (2.0) .68.........................................................................................................................
6 (0.7) 6 (0.7) .88.........................................................................................................................
12 (3.2) 13 (2.6) .59.........................................................................................................................
11 (11.6) 11 (7.5) .28........................................................................................................................
.........................................................................................................................
259 (12.3) 264 (9.3) .0006.........................................................................................................................
43 (4.6) 39 (3.6) .26.........................................................................................................................
89 (11.4) 78 (7.0) .0009.........................................................................................................................
117 (38.6) 123 (24.7) .0001........................................................................................................................
.........................................................................................................................
212 (53.9) 212 (34.0) .0001.........................................................................................................................
47 (37.9) 29 (16.8) .0001.........................................................................................................................
86 (54.8) 76 (31.0) .0001.........................................................................................................................
74 (74.8) 101 (59.8) .01........................................................................................................................
.........................................................................................................................
55 (42.0) 87 (32.2) .06.........................................................................................................................
20 (39.2) 20 (20.4) .01.........................................................................................................................
23 (43.4) 40 (37.0) .44.........................................................................................................................
9 (50.0) 19 (46.3) .80........................................................................................................................
.........................................................................................................................
94 (64.8) 165 (51.6) .008.........................................................................................................................
19 (51.4) 42 (45.2) .52.........................................................................................................................
46 (69.7) 62 (47.7) .003.........................................................................................................................
22 (68.8) 49 (64.5) .67........................................................................................................................
nown tumor grade.
Gynecol 2011.s not inferior to whole pelvic radia- co
DECEMBER 2011 Americann.28Thesedata suggest thatwholepelviciation can safely be omitted in favor ofchytherapy in those patients with cor-s-confined disease inwhom radiation iscted.atients with unstaged endometrialcer present a difficult dilemma in thatinal brachytherapy is inadequateatment for womenwith unrecognizeddal disease. Although lymphadenec-y was not required for entry into theRTEC-2 trial, it is unclear whethernicians in the United States would
aginal brachytherapy
-9 nodes,(%)
>10 nodes,n (%) P value
............................................................................................................
21 (1.6) 28 (1.7) .75............................................................................................................
8 (1.0) 6 (0.7) .49............................................................................................................
5 (1.3) 8 (1.6) .75............................................................................................................
5 (5.3) 8 (5.4) .95...........................................................................................................
............................................................................................................
28 (6.1) 247 (8.7) .0007............................................................................................................
31 (3.3) 45 (4.2) .32............................................................................................................
55 (7.0) 99 (8.9) .15............................................................................................................
34 (11.2) 80 (16.1) .06...........................................................................................................
............................................................................................................
32 (8.1) 94 (15.1) .001............................................................................................................
13 (10.5) 28 (16.2) .16............................................................................................................
11 (7.0) 33 (13.5) .04............................................................................................................
5 (5.1) 15 (8.9) .25...........................................................................................................
............................................................................................................
20 (15.3) 59 (22.9) .12............................................................................................................
9 (17.7) 20 (20.4) .69............................................................................................................
7 (13.2) 26 (24.1) .11............................................................................................................
1 (5.6) 6 (14.6) .32...........................................................................................................
............................................................................................................
8 (5.5) 42 (13.1) .01............................................................................................................
3 (8.1) 17 (18.3) .15............................................................................................................
3 (4.6) 19 (14.6) .03............................................................................................................
2 (6.3) 5 (6.6) .95...........................................................................................................anwiingwian
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Journal of Obstetrics& Gynecology 562.e6
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Research Oncology www.AJOG.org
56ate treatment for women with un-ged high-intermediate risk disease. Avey of US gynecologic oncologists re-rted that these physicians were 23%s likely to administer radiation tomen with grade 1 tumors with 50-%myoinvasion inwomenwhounder-nt lymphadenectomy compared withtients who had not undergone nodalluation.30
Whereas pelvic radiation is generallyll tolerated, treatment is associatedth an increased risk of both acute and
TABLE 5Effect of extent of lymphadenectomyin women 60 years of age or older w
Variable Total
1-9lymphnodes
>10lymphnodes
A................................................................................................................
All IA 2412 1136 1276................................................................................................................
Grade 1 1064 534 530................................................................................................................
Grade 2 799 375 424................................................................................................................
Grade 3 399 154 245.........................................................................................................................
IB................................................................................................................
All IB 6793 3083 3710................................................................................................................
Grade 1 2312 1132 1180................................................................................................................
Grade 2 2830 1294 1536................................................................................................................
Grade 3 1325 529 796.........................................................................................................................
IC................................................................................................................
All IC 3416 1539 1877................................................................................................................
Grade 1 901 426 475................................................................................................................
Grade 2 1496 695 801................................................................................................................
Grade 3 869 370 499.........................................................................................................................
IIA................................................................................................................
All IIA 539 214 325................................................................................................................
Grade 1 152 65 87................................................................................................................
Grade 2 221 81 140................................................................................................................
Grade 3 132 53 79.........................................................................................................................
IIB................................................................................................................
All IIB 558 213 345................................................................................................................
Grade 1 121 43 78................................................................................................................
Grade 2 234 99 135................................................................................................................
Grade 3 157 62 95.........................................................................................................................
Total number of patients for each substage includes patients with
Sharma. Lymphadenectomy for endometrial cancer. Am J Obe toxicities2,22,23,28 In the GOGs eval- ter
2.e7 American Journal of Obstetrics& Gynecologytion of pelvic radiation for interme-te-risk endometrial cancer, treat-nt was associated with an increasedk of hematologic, gastrointestinal,nitourinary, and cutaneous compli-ions.23 The side effect profile of ra-tion is improved when vaginalachytherapy is substituted for exter-l beam treatment. The PORTEC-2estigators noted that the rate of gas-intestinal toxicity was 4-fold lowerpatients treated with brachytherapympared with those who received ex-
-9 vs >10 nodes) on use of radiationunderwent nodal evaluation
External beam radiation
1-9 nodes,n (%)
>10 nodes,n (%) P value
.........................................................................................................................
49 (4.3) 45 (3.5) .32.........................................................................................................................
15 (2.8) 9 (1.7) .22.........................................................................................................................
18 (4.8) 15 (3.5) .37.........................................................................................................................
12 (7.8) 17 (6.9) .75........................................................................................................................
.........................................................................................................................
410 (13.3) 394 (10.6) .0007.........................................................................................................................
60 (5.3) 46 (3.9) .11.........................................................................................................................
142 (11.0) 120 (7.8) .004.........................................................................................................................
190 (35.9) 200 (25.1) .0001........................................................................................................................
.........................................................................................................................
744 (48.3) 646 (34.4) .0001.........................................................................................................................
169 (39.7) 90 (19.0) .0001.........................................................................................................................
340 (48.9) 286 (35.7) .0001.........................................................................................................................
219 (59.2) 238 (47.7) .0008........................................................................................................................
.........................................................................................................................
102 (47.7) 71 (21.9) .0001.........................................................................................................................
22 (33.9) 12 (13.8) .003.........................................................................................................................
38 (46.9) 30 (21.4) .0001.........................................................................................................................
39 (73.6) 28 (35.4) .0001........................................................................................................................
.........................................................................................................................
115 (54.0) 183 (53.0) .83.........................................................................................................................
23 (53.5) 39 (50.0) .71.........................................................................................................................
55 (55.6) 60 (44.4) .09.........................................................................................................................
33 (53.2) 59 (62.1) .27........................................................................................................................
nown tumor grade.
Gynecol 2011.nal beam radiation.28 sta
DECEMBER 2011In addition to toxicity, pelvic radio-rapy is associated with significantsts to the health care system.31,32 A re-t decision analysis reported the meanst of external beam pelvic radiation asre than $9000.31 In addition to directsts, pelvic radiotherapy is typically ad-nistered over a course of 5-6 weeksd requires a significant time commit-nt from patients. In our analysis, per-mance of lymphadenectomy in only 5tients younger than 60 years of age or 7tients older than 60 years of age with
aginal brachytherapy
-9 nodes,(%)
>10 nodes,n (%) P value
............................................................................................................
24 (2.1) 27 (2.1) 1.00............................................................................................................
5 (0.9) 1 (0.2) .10............................................................................................................
11 (2.9) 9 (2.1) .46............................................................................................................
5 (3.3) 13 (5.3) .33...........................................................................................................
............................................................................................................
95 (6.3) 352 (9.5) .0001............................................................................................................
42 (3.7) 43 (3.6) .93............................................................................................................
92 (7.1) 140 (9.1) .05............................................................................................................
40 (7.6) 134 (16.8)...........................................................................................................
............................................................................................................
00 (6.5) 294 (15.7) .0001............................................................................................................
35 (8.2) 66 (13.9) .007............................................................................................................
45 (6.5) 125 (15.6) .0001............................................................................................................
12 (3.2) 68 (13.6) .0001...........................................................................................................
............................................................................................................
29 (13.6) 83 (25.5) .0008............................................................................................................
10 (15.4) 22 (25.3) .14............................................................................................................
10 (12.4) 43 (30.7) .002............................................................................................................
4 (7.6) 10 (12.7) .35...........................................................................................................
............................................................................................................
18 (8.5) 49 (14.2) .04............................................................................................................
4 (9.3) 13 (16.7) .26............................................................................................................
7 (7.1) 18 (13.3) .13............................................................................................................
6 (9.7) 12 (12.6) .57...........................................................................................................uadiamerisgecatdiabrnainvtroinco
thecocencomocomianmeforpapa
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REF1. Jtist2772. APoticmapat3. CHopatcerCa4. MRefaccarOn40:5. Ccinste6. BTwendpoOn7. CK,witnec8. CReneccan
mepat10.Adcomnod11.PalymAS20012.al.lymcarcer13.ASapyOn14.P.adjcan15.Griinaate20016.efitnodcer17.Stasurtienapy18.ReCacan19.sulregNaCoRerele200gov20.lymnec21.extendCTsulLan22.etverenddo
www.AJOG.org Oncology Researchired to avoid 1 course of pelviciation.The most important question ad-ssed by our study is which patientsrive the most benefit from lymphade-ctomy. Our findings suggest that pa-nts with stage IB and IC tumors arest likely to have their adjuvant treat-nt influenced by lymphadenectomy.hough prior work has demonstrateddifficulty in predicting final tumor
de and depth of invasion based on pre-erative biopsy and intraoperative in-ction, we noted that even women with-grade, superficially invasive tumorsre less likely to receive pelvic radiation ify underwent lymphadenectomy.33-36
We also noted that the extent ofphadenectomy performed appearedinfluence treatment allocation. Theuced use of external beam radiationong patients with intermediate riskors was most pronounced in pa-
nts who had 10 or more nodes re-ved. Although prior studies of endo-trial cancer have suggested that theent of lymphadenectomy influencesvival, our data suggest that nodeunt also has a direct impact on the al-ation of adjuvant treatment.Although our analysis benefits frominclusion of a large number of pa-
nts, we recognize several importantitations. Because SEER lacks data onemotherapy, our study was limited tomining the influence of lymphadenc-y on the prescription of radiother-
y. Although uncommon during thers of study, adjuvant chemotherapywomen with early-stage endometrialcer is now more frequently uti-
ed.37,38 Although SEER captures datathe type of radiation administered,database lacks details on total dose ofiation, treatment fields, and durationtreatment.Given these limitations, we restrictedr analysis to simply determiningether external beam radiation orchytherapy was administered. Ourdy utilized the 1988 FIGO staging crite-. FIGO has recently implemented a re-ed staging schema, and our findingsy have differed somewhat using the up-ted system. Finally, although we strati-
d our analysis by 3 of the factors most
9. Capeportant in theuseof adjuvant treatmente, stage, and grade), a number of indi-ual patient and physician factors haveimpact on the allocation of treatmentdmay have influenced our results.Our findings suggest that lymphade-ctomy plays an important role in theocation of adjuvant treatment formen with stage I and II endometrialcer. Those women who undergophadenectomy are less likely to re-ve whole pelvic radiotherapy. The ef-ts of lymphadenectomy are mostnounced in women with high-inter-diate risk tumors and greatest for pa-nts who have 10 or more nodes re-ved. In aggregate are data supportphadenectomy for the majority ofmen with endometrial cancer. Thosemenwhoundergo lymphadenectomyuld have at least 10 nodes removed ascified by the GOG.20 f
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Research Oncology www.AJOG.org
562.e9 American Journal of Obstetrics& Gynecology DECEMBER 2011
Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancerMaterials and MethodsResultsCommentReferences