Initial experience with positron emission tomography/computed tomography in addition to computed tomography and magnetic resonance imaging in preoperative risk assessment of endometrial cancer patients

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Full length article

Initial experience with positron emission tomography/computed tomography in addition to computed tomography and magnetic resonance imaging in preoperative risk assessment of

endometrial cancer patients

Nina Jebens Nordskar

^a,b,

*, Bjørn Hagen

^a

, Aleksei Ogarkov

^c

, Ellen V. Vesterfjell

^d

, Øyvind Salvesen

^e

, Guro Aune

^a,b

aDepartmentofGynecologicOncology,Dept.ofObstetricsandGynecology,StOlav’sHospital,TrondheimUniversityHospital,7006,Trondheim,Norway

bDepartmentofClinicalandMolecularMedicine,NorwegianUniversityofScienceandTechnology,7491Trondheim,Norway

cDepartmentofRadiologyandNuclearMedicine,StOlav’sHospital,TrondheimUniversityHospital,7006,Trondheim,Norway

dDepartmentofPathology,StOlav’sHospital,TrondheimUniversityHospital,7006,Trondheim,Norway

eUnitofAppliedClinicalResearch,DepartmentofPublicHealthandNursing,FacultyofMedicineandHealthScience,NorwegianUniversityofScienceand Technology,Trondheim,Norway

ARTICLE INFO Articlehistory:

Received27November2020

Receivedinrevisedform19January2021 Accepted26January2021

Keywords:

Endometrialcancer PET

Imaging

Sentinellymphnode Lymphnodemetastases

ABSTRACT

Objective: Improved preoperative evaluation of lymph node status could potentially replace lymphadenectomy in womenwith endometrial cancer. PET/CTwas routinely implemented in the preoperativeworkupofendometrialcanceratStOlav’sUniversityHospitalin2016.ExperiencewithPET/

CTislimited,andthereisnoconsensusabouttheuseofPET/CTinthediagnosticworkupofendometrial cancer.TheaimofthestudywastoevaluatethediagnosticaccuracyofPET/CTcomparedtostandardCT/

MRIinidentifyinglymphnodemetastasesinendometrialcancerwithhistologicallyconﬁrmedlymph nodemetastasesasthestandardofreference.WeespeciallywantedtolookatPET/CTasasupplementto thesentinellymphnodealgorithminthedetectionofparaaorticlymphnodes.

Studydesign:Aretrospectivestudyincludedallwomenundergoingsurgeryforendometrialcancerfrom January2016throughJuly2019atStOlav’sUniversityHospital.Clinicaldata,resultsofCT,MRI,andPET/

CT,andhistopathologicalresultswereanalyzed.

Results:Among185patientsincluded,27patients(15%)hadlymphnodemetastases.17(63%)hadpelvic lymphnodemetastases,one(4%)hadisolatedparaaorticlymphnodemetastases,and9(33%)hadlymph nodemetastases in both thepelvis and the paraaortic region.The sensitivity, speciﬁcity, positive predictivevalue,negativepredictivevalueandaccuracyofPET/CTforthedetectionoflymphnode metastaseswere63%,98%,85%,94%,and93%,respectively.Thesensitivity, speciﬁcity,positive predictivevalue,negativepredictivevalueandaccuracyofCT/MRIwere41%,98%,73%,91%,and90%, respectively(p=0.07).Forthe26pelviclymphnodemetastases,PET/CThadasensitivityof58%, comparedto42%forCT/MRI(p=0.22).PET/CTdetectedall10paraaorticlymphnodemetastases,fora sensitivityof100%,comparedto50%forCT/MRI(p=0.06).

Conclusions:PETissuperiortoCT/MRIfordetectionoflymphnodemetastasesinendometrialcancer, particularlyindetectingparaaorticlymphnodemetastases.TheabilityofpreoperativePETtoexclude paraaorticlymphnodemetastasesmaystrengthenthecredibilityofthesentinellymphnodealgorithm.

*Correspondingauthor.

E-mailaddresses:nina.j.nordskar@ntnu.no,nina.jebens.nordskar@stolav.no(N.J.Nordskar),hagenbjo7@gmail.com(B.Hagen),aleksei.ogarkov@stolav.no(A.Ogarkov), ellen.veronika.vesterfjell@stolav.no(E.V. Vesterfjell),oyvind.salvesen@ntnu.no(Ø.Salvesen),guro.aune@ntnu.no(G.Aune).

https://doi.org/10.1016/j.ejogrb.2021.01.052

ContentslistsavailableatScienceDirect

European Journal of Obstetrics & Gynecology and Reproductive Biology

j o u r n a l h o m e p a g e : w w w . e l s ev i er . c o m / l o c a t e/ e j o g r b

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Introduction

Primarysurgery forapparentearly-stageendometrial cancer includes hysterectomy, bilateral salpingo-oophorectomy, and assessment of regional lymphnode involvement.Lymph nodes arethemostcommonsiteofextrauterinespread[1,2].Detecting lymph nodemetastases in endometrial canceris important for treatmentandprognosis[3–6].It isdebatedifparaaorticnodes shouldberemoved,andwhethercomprehensivelymphadenecto- my improves prognosis, at the cost of increased complications [3,4,7].Thesentinellymphnode(SLN)strategyhasemergedasa compromisebetweencomprehensivelymphadenectomyinhigh- risk patientsandomittance oflymphnoderemovalinlow-risk patients,allowingsufﬁcientlymphnodeassessmentinpatientsof allriskcategories[8].

Preoperative imaging provides important guidance in the choiceofsurgicalprocedure,especiallyasdetectionofsuspicious paraaorticlymphnodesentailsoperationbylaparotomyinsteadof minimally invasive surgery and SLN. Standard preoperative diagnostictoolsinendometrialcancerarecomputedtomography (CT)andmagneticresonanceimaging(MRI)[9–12].Thedevelop- mentofpositronemissiontomography(PET)/CTcombinesCTwith radiolabeled ¹⁸F-ﬂuorodeoxyglucose (FDG), potentially allowing detectionofsmallvolumediseaseoverlookedonCTandMRI.Since 2016, whole body FDG PET/CT has been included in the preoperative diagnostic workup of endometrial cancer in our hospital.However,experienceandconsensusabouttheuseofPET/

CTinthediagnosticworkupofendometrialcancerarelimited[9].

The aimof thepresentstudywastoevaluatethediagnostic accuracyof PET/CTcompared tostandard CT/MRIin identifying lymph nodemetastases in endometrialcancer, and particularly withregardtoevaluationoftheparaaorticregionincandidatesfor SLN-mapping.

Materialsandmethods Patientpopulation

Patients with histologically conﬁrmed endometrial cancer, operatedintheperiodfrom2016throughJuly2019,wereeligible toparticipateinaretrospectiveobservationalstudy.Wecompared

theabilityofpreoperativePET/CTversuspreoperativeCT/MRIto detect lymph node metastases, with histologically conﬁrmed lymph node metastases as the standard of reference. In our hospital, PET/CTwas implementedas routine in 2016, and the sentinellymphnode(SLN)mappingalgorithmhasbeenusedsince 2012[13].

Inclusion criteria were histologically conﬁrmed endometrial cancer,preoperativeCTofthethorax,abdomen,andpelvis,MRIof the pelvis, preoperative ¹⁸F-FDG PET/CT, pelvic lymph node removal,and histologicallyconﬁrmedpresence oflymphnodes (Fig.1).

Inaddition,patientsoperatedbetweenNovember2012through 2015 were included as a reference group, to determine if the addition of PET/CT had any inﬂuence on the performance and interpretationofCT/MRI.Patientsinthereferencegroupwhohada PET/CTscanperformedinthepreoperativeworkupofendometrial cancerwereexcluded.

Thepatientswerepreoperativelyclassiﬁedintotraditionalrisk categories,basedonhistopathologicaltypeandgrade,anddepthof myometrialinﬁltrationassessedbypreoperativeimaging.

Preoperativeimaging

The PET/CT procedure was performed according to the institutional standard with ¹⁸F-FDG (4 M Bq/kg) injection following 6 hfasting. Blood glucose was controlled tobe <10 nmol/l.PET/CTfromthevertextothemiddlefemurwasobtained 60minafterFDG injection.3D imagereconstructionwas made using256256matrix,4mmFWHM,TimeOfFlightandPoint SpreadFunction.AllstudieswereperformedonSiemensBiograph mCT.Theimageswereassessedbyexperiencednuclearmedicine physicians.

The classiﬁcation of lymph nodes on PET/CT as imaging- suspiciouswasbasedonthepresenceoffocallyincreasedFDG uptakecomparedtothebackgrounduptakeinbloodandinthe liver,andonthesize,shape,symmetryandlocationofthelymph node.The classiﬁcationof lymphnodesasimaging-suspicious onCTandMRIwasbasedonsize,shapeandlocation.According totheclinicalpathwayforendometrialcancer,thepreoperative assessment is completed within 36 days from the time of referral.

Fig.1.Studypopulation.

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Surgicaltreatment

Allpatientsunderwenthysterectomy,bilateralsalpingo-oophorectomy andpelviclymphnoderemoval.Patientswithapparent earlystagediseaseunderwent robot-assisted laparoscopicoperation with pelvicSLN mapping using indocyanine green ﬂuorescence followingtheMemorialSloanKetteringsurgicalalgorithm[13,14].

Patientswithuterinesize>8cmorimaging-suspiciouslymphnodes cranialtotheleveloftheinferiormesentericarteryhadhysterecto- my,bilateralsalpingo-oophorectomy,andconventionallymphnode removal(pelvicandeventuallyparaaortic)withoutSLNmappingby laparotomy.

Pelvic lymph node removal in addition to SLNs included removal of all imaging-suspicious lymph nodes, perioperative enlargedorﬁxedlymphnodes,orsamplingoflymphnodesfrom theexternaliliacandobturator fossa.Somepatientsunderwent additional paraaortic lymph node dissection, performed at the discretion of the surgeon, including imaging-suspicious lymph nodes,orsamplingoflymphnodesbelowtheinferiormesenteric artery.

Histopathologicalevaluationoflymphnodes

Thesurgicalspecimensunderwentstandardhistopathological examination after formalin ﬁxation and hematoxylin-eosin staining. For the patients undergoing SLN mapping, routine histologynegativeSLNswerefurtherexaminedwithultrastaging, including additionalsectioning andimmunohistochemistry for cytokeratin. Lymph node metastases were categorized into macro-metastases(>2mm)andmicro-metastases(0.2–2mm).

Isolatedtumorcells(<0.2mm)werenotdeﬁnedaslymphnode metastasesandtheisolatedtumorcellscategorywasdiagnosed onlywhenthetumorfocuswasvisibleinboththehematoxylin- eosin and the adjacent immunohistochemistry sections. The histopathological evaluation was performed by experienced gynecologiconcologypathologists.

Statistics

Patients characteristics were summarized using the median (range) forcontinuousvariablesand percentagesforcategorical variables. The result of the histological evaluation was set as standard of reference for statistical analyses of lymph node metastases.DifferencesinsensitivityandspeciﬁcitybetweenPET/

CT and CT/MRI wereexamined using theMcNemar exact test.

Comparisonof lymphnodedetectionwithCT/MRIbetweenthe studygroupandthereferencegroupwasperformedwiththeChi square test. For all analyses, p-values less than 0.05 were considered statistically signiﬁcant. Statistical analyses were performed using International Business Machines Corporation (IBM)StatisticalPackagefortheSocialScience(SPSS),version27.

Ethics

The study was approved by the Regional Committees for MedicalandHealthResearchEthics(REKmidt7193/2019).

Results

Patientpopulation

A total of 255 patients underwent primary surgery due to endometrialcancerinthestudyperiod.Ofthe238patientswho consented to participate, 185 fulﬁlled the inclusion criteria, constituting the study population (Fig. 1). Demographic and clinicalcharacteristicsaregiveninTable1.

Inthestudygroup,132/185(71%)underwentrobot-assisted laparoscopicsurgery,and53/185(29%)laparotomy.Pelviclymph noderemovalwithSLNmappingwasperformedin130/132(98%) oftherobot-assistedcases.

Ofthe185patientsinthestudygroup,168(91%)hada PET positive uterine tumor. Of the 17 patients with PET negative uterinetumors,14hadstage1A,onestage1B.Twopatientshad stage3Cdue tolymphnodespread, both haduterine stage1A disease,onehadPETnegativewhileonehadPETpositivelymph nodemetastases.

Prevalenceofmetastaticdisease

Theoverallmetastaticratewas19%(35/185).

Prevalenceoflymphnodemetastases

Thelymphnodemetastaticratewas15%(27/185).Seventeen (63 %) had pelvic lymph node metastases,1 (4%) had isolated paraaorticlymphnodemetastases,and9(33%)hadmetastasesin bothregions.

Sizeoflymphnodemetastases

Themediansizeof thelymphnodemetastases was4.5mm (0.20–80.0mm).Fourteenoutof27(52%)weremacro-metastases and13/27(48%)micro-metastases.Additionally,isolatedtumor cells(<0.2mm)weredetectedin12patients(6%).Thecharacter- istics ofthe patientswithlymphnodemetastases are givenin Table2.

Non-lymphaticmetastases

Fifteen patients (8%) had non-lymphatic spread of disease.

Elevenhadspreadoftumortotheovaryorthefallopiantube,the Table1

Demographicandclinicalcharacteristics(N=185).

Median Range

Age(years) 69.0 39 88

Bodymassindex(kg/m²) 28.1* 16.6 53.7

Operationtime(minutes) 109 65 312

Bloodloss(milliliters) 50 0 1920

N Percentage

Histologictype

Endometrioid 134 72.4

Serous 20 10.8

Clearcell 9 4.9

Carcinosarcoma 5 2.7

Mixed 8 4.3

Others 9 4.9

FIGOstage

IA 96 51.9

IB 47 25.4

II 5 2.7

IIIA 8 4.3

IIIB

IIIC 26 14.1

IV 3 1.6

Blood-orlymphvascularspaceinvasion

No 142 76.8

Yes 43 23.2

Postoperativechemotherapy

No 115 62.2

Yes 70 37.8

Operationmethod

RoboticwithSLN 130 70.3

RoboticwithoutSLN 2 1.1

Laparotomy 53 28.6

* Threemissingbodymassindexes.

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remaining four patients to the omentum, lung/skeleton, small bowelserosa,orthepouchofDouglas.Preoperativedetectionof non-lymphaticmetastaseswas5/15(33%)withPET/CTcompared to4/15(27%)withCT/MRI.

Lymphnodeﬁndingsonpre-operativeimaging

ThesensitivitytodetectmetastaticnodeswashigherforPET/CT thanforCT/MRI.Lymphnodemetastasesweredetectedin17/27 (63 %)patientsonPET/CT, comparedto 11/27 (41%) onCT/MRI (p = 0.07). The sensitivity, speciﬁcity, positive predictive value, negativepredictivevalue,accuracyandlikelihoodratiosforPET/CT andCT/MRIarepresentedinTable3.Ofthe26patientswithpelvic lymphnodemetastases,thesemetastasesweredetectedin15(58%)

onPET/CT,andin11(42%)onCT/MRI(p=0.22).Ofthe10patients with paraaortic lymph node metastases,these metastaseswere detectedin10(100%)onPET/CT,and5(50%)onCT/MRI(p=0.06) (Fig.2).Onepatienthadisolatedparaaorticlymphnodemetastases whichwasdetectedonPET/CT,butnotonCT/MRI.

Sizeoflymphnodemetastases

ThemediansizeofmetastasesdetectedonPET/CTwas17.0mm (0.5–80.0mm)andonCT/MRI20.0mm(0.6–80.0 mm).Macro- metastases weremore often detected onPET/CT:13/14 (93%), compared to CT/MRI: 8/14 (57 %), (p = 0.06). There was no differenceinthedetectionofmicro-metastases,4/13(31%)onPET/

CTversus3/13(23%)onCT/MRI(p=1.0).

Themediansizeoflymphnodemetastasesnotdetectedwas0.5 mm(0.2–4.5mm)forPET/CTand1.2mm(0.2–18.0mm)forCT/

MRI.

Amongthe12casesofisolatedtumorcellsinlymphnodes,all wereCT/MRInegative,whileone(8%)wasPETpositive.

Detectionoflymphnodemetastasesindifferentriskcategories Thedistributionofpreoperativeuterineriskcategorieswas39% low-risk,30%intermediate-riskand28%high-risk.Sixpatients couldnot becategorized intoa preoperative risk groupdue to insufﬁcient preoperativehistology. Thepresenceoflymphnode metastasesinthedifferentriskgroups,andthedetectionratesfor PET/CTandCT/MRIareshowninTable4.

DetectionintheSLNgroup

InthepatientstreatedwiththeSLNalgorithm,thesensitivity, speciﬁcity and accuracy for PET/CTwas 29 %, 98 %,and 91 %, comparedto21%,98%,and90%forCT/MRI.

Table2

Characteristicsofpatientswithlymphnodemetastases.

Case Histology Grade Riskcategory* Diameteroflargest lymphnodemetastasis (mm)

Location Metastaticlymph node(s)onPET/CT

Metastaticlymph node(s)onCT/MR

Metastaticlymph nodeinSLNor non-SLN

1 Endometrioid 1 Low 20 Pelvic Pelvic Pelvic SLN

2 Endometrioid 1 Intermediate 0.3 Pelvic Negative Negative SLN

5 Endometrioid 2 Low 0.6 Pelvic Negative Pelvic SLN

7 Endometrioid 2 Intermediate 0.5 Pelvic Pelvic Negative SLN

8 Endometrioid 2 Intermediate 0.7 Paraaortic Paraaortic Negative Non-SLN***

9 Endometrioid 2 Intermediate 9 Pelvic+paraaortic Pelvic+paraaortic Pelvic+paraaortic Non-SLN***

11 Endometrioid 3 Intermediate 0.3 Pelvic Negative** Negative SLN

12 Endometrioid 3 Intermediate 12 Pelvic+paraaortic Pelvic+paraaortic Negative Non-SLN***

13 Endometrioid 3 High 6 Pelvic+paraaortic Pelvic+paraaortic Negative Non-SLN***

14 Endometrioid+serous 2 High 5 Pelvic Pelvic Pelvic SLN

15 Endometrioid+serous 3 High 1.5 Pelvic Pelvic Pelvic Non-SLN***

16 Serous High 1 Pelvic Pelvic Pelvic Non-SLN***

17 Serous High 17 Pelvic+paraaortic Paraaortic** Negative Non-SLN****

18 Serous High 18 Pelvic+paraaortic Pelvic+paraaortic Negative Non-SLN***

19 Serous High 24 Pelvic+paraaortic Pelvic+paraaortic Pelvic+paraaortic Non-SLN***

20 Serous High 25 Pelvic+paraaortic Pelvic+paraaortic Pelvic+paraaortic Non-SLN***

21 Clearcell High 0.4 Pelvic Negative Negative SLN

22 Clearcell Inconclusive 42 Pelvic+paraaortic Pelvic+paraaortic Pelvic+paraaortic Non-SLN***

23 Carcinosarcoma High 0.9 Pelvic Negative Negative SLN

24 Carcinosarcoma High 2 Pelvic Negative Negative SLN

25 Carcinosarcoma High 18 Pelvic Pelvic Negative Non-SLN***

26 Carcinosarcoma High 29 Pelvic Pelvic Pelvic Non-SLN***

27 Neuroendocrine High 80 Pelvic+paraaortic Pelvic+paraaortic Pelvic+paraaortic Non-SLN***

*Riskcategory:Basedonhistopathologicaltypeandgrade,anddepthofmyometrialinﬁltration(assessedbypreoperativeimaging).

**TumorPETnegative.

*** Operatedbylaparotomy.

****Convertedtolaparotomy.

Table3

Preoperative detection of lymphnode metastases onPET/CTand CT/MRI by histopathologyinremovedlymphnodesinthestudygroup.

Histopathology Total

Positive Negative

PET/CT Positive 17 3 20

Negative 10 155 165

CT/MRI Positive 11 4 15

Negative 16 154 170

Total#(%) 27(15) 158(85) 185

PET/CT:Sensitivity63.0%.Positivepredictivevalue85.0%.Speciﬁcity98.1%.

Negativepredictivevalue93.9%.Accuracy93.0%.Positivelikelihoodratio32.5, negativelikelihoodratio0.38.

CT/MRI:Sensitivity40.7%.Positivepredictivevalue73.3%.Speciﬁcity97.5%.

Negativepredictivevalue90.6%.Accuracy89.2%.Positivelikelihoodratio16.1, negativelikelihoodratio0.61.

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Detectionrateinthereferencegroup

Lymph node metastases were detected in 36 of those 173 patients(21%)operatedbefore2016(referencegroup).Therewas no statisticallysigniﬁcant difference in the detection of lymph nodemetastasesonpreoperativeCT/MRIbetweenthereference group and thestudy group; 20/36 (56 %) versus 11/27(41 %), respectively(p=0.244).

Discussion

ThepresentstudyindicatesadiagnosticvalueofPET/CTinthe preoperativework-upofendometrialcancerpatients,especiallyin detectingparaaorticlymphnodemetastases.Severalstudieshave suggesteda prognosticbeneﬁtof surgicalremoval ofmetastatic paraaortic lymph nodes [15–17]. In our study, all paraaortic Fig.2. PET/CTimages(left)showingmetastaticparaaorticlymphnodeoverseenonCT(right).Thepicturesarepublishedwiththepatient’sconsent.

Table4

Thedistributionofriskcategories,correspondingratesoflymphnode(LN)metastasesanddetectionbyCT/MRIvsPET/CT.

Preoperative riskcategory

Numberof patients(%)

NumberwithLN metastases(%)

NumberofLNmetastases detectedonPET/CT(%)

NumberofLNmetastases detectedonCT/MRI(%)

Low 73(39) 2(3) 1(50) 2(100)

Intermediate 55(30) 10(18) 4(40) 1(10)

High 51(28) 14(27) 11(79) 7(50)

Missing 6(3) 1(17) 1(100) 1(100)

Total 185 27

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metastasesweredetectedonPET/CT,butonlyhalfofthemonCT/

MRI.Mostofthepatientswithparaaorticlymphnodemetastases alsohadpelviclymphnodemetastases,butonepatienthadisolated paraaorticlymphnodemetastases,onlydetectedonPET/CT.

Wefoundasensitivityof63%andaspecificityof98%todetect lymphnodemetastaseswithPET/CT.Changetal.foundasimilar sensitivityof63%andaspecificityof95%inameta-analysisof243 endometrialcancerpatients[18].Inameta-analysisincluding861 patients,Bollinenietal.foundasensitivityof72%andaspecificity of94%[19].

Theidentiﬁcation ofmetastaticlymphnodesonbothCTand MRIisbasedonmeasurementsofnodesize.Acommonthreshold forconsideringalymphnodemetastaticis8 10mm[11,20–25].

However,itisachallengetodifferentiatemetastaticlymphnodes frombenignreactivenodesofsimilarsize,andmetastaticlymph nodesofnormalsizeandenlargedreactivelymphnodescanbe misclassiﬁed [23,25]. PET/CT provides functional data due to increased glucosemetabolism inmalignant cells, and therefore PET/CTispotentiallyabletodetectsmallerlymphnodemetastases thanCTandMRI.

Wefoundarelativelyhighrateoffalsenegativelymphnode metastasesonPET/CT.CurrentPET/CTtechnologyhaslowspatial resolutionandcanonlydetectlesionswithasufﬁcientnumberof metabolicallyactivemalignantcells[9,18,26,27].Themeanvalue ofspatialresolutioninPETis5mm[21,23,28].Thislimitedspatial resolutionmakesthepresenceofmetastasesinsmalllymphnodes hardlydetectable.

Inourstudy,PET/CTdetected93%ofthemacro-metastasesand 31%ofthemicro-metastases.Incomparison,CT/MRIdetected57% of themacro-metastasesand23 %ofthemicro-metastases.The mediansizeofthelymphnodemetastasesnotdetectedonPET/CT was 0.5 mm, whereas the median size of the lymph node metastases notdetectedonCT/MRIwas0.9 mm.Kitajimaetal.

foundadetectionrateonPET/CTofonly12.5%inmetastaticlymph nodesmeasuring4mmorless,but100%whenthelymphnodes were10mmorlarger[21].Budaketal.founda0%detectionratefor lymphnodemetastases4mmorless,buta100%detectionratefor lymphnodemetastases10mmorlarger[20].

Therelatively highrateoffalsenegative PET/CTresultsmay partlyberelatedtotheSLNultra-stagingtechnique,whichallows detectionofmicro-metastaticdepositstoosmallfordetectionon PET/CT[29].Mostpatientsinourstudyunderwentrobot-assisted laparoscopic surgery with sentinel lymph node removal and ultra-staging. Tanakaet al. compared thecombineddiagnostic accuracyofFDG-PET/CTandsentinellymphnodebiopsyinthe prediction of pelvic lymph node metastases in endometrial cancer.TheyfoundthatPET/CThadlowersensitivityforlymph nodemetastasescomparedtosentinelnodebiopsy(36.8%versus 57.9%),especiallyinpatientswithsmallmetastaticlymphnodes [30]. However, the sensitivity was higher for PET/CT than for sentinelnodebiopsyinlymphnodemetastases5mm(62.5% versus 37.5%).ThelimitedsensitivityofPET/CTindetectionof metastaticlymphnodesinlow-/intermediate-riskpatientsinour studyemphasizestheimportanceofSLNinendometrialcancer patients.

The omittance of paraaortic nodes in SLN algorithms is a potential limitation.Taskinetal.recentlyevaluatedthecomple- mentaryroleofPET/CTinthesentinellymphnodealgorithmin high-risk patients. In their studyof 38 patients, two outof 10 patients with lymph node metastases had isolated paraaortic metastasesdiagnosedonlyonPET/CT[31].

Limitationsofourstudyincludetheretrospectivestudydesign andfewpatientswithlymphnodemetastases.Further,evaluation of PET/CTand CT/MRIwas performed unblindedbythe radiol- ogists. To address this, we investigated the detection of lymphnodemetastasesbyCT/MRIbeforeandafterPET/CTwas

introduced,anddidnotﬁndimprovedCT/MRIdetectionafterthe introductionofPET/CT.

InourstudywehaveperformedPETonlyincombinationwith CT(PET/CT)andused¹⁸F-FDGastracer.StudiesonPET/MRIanduse ofothertracershaveshownvariousresultsandshouldbefurther explored[10,32–39].

Conclusion

In conclusion, PET/CT was superior to CT and MRI in the detectionoflymphnodemetastasesinendometrialcancer.PET/CT hasadiagnosticvalue,inparticularindetectingparaaorticlymph nodespreadinendometrialcancerpatientsthatarecandidatesfor minimal access surgery with SLN mapping. It is reasonable to continue performing PET/CT in the preoperative evaluation of patientswithendometrialcancer.

DeclarationofCompetingInterest

Theauthorsreportnodeclarationsofinterest.

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Nina Jebens Nordskar, MD Corresponding author Section of Gynecologic Oncology, Dept. of Obstetrics andGynecology,StOlav’shospital,TrondheimUniversity Hospital. Nina Jebens Nordskar is an experienced gynecologist under sub specialization in gynecologic oncology.SheisdoingherPhDatNTNU,Departmentof ClinicalandMolecularMedicine

BjørnHagen,MDPhDCoauthorSectionofGynecologic Oncology,Dept.ofObstetricsandGynecology,StOlav’s hospital,TrondheimUniversityHospital.BjørnHagenis an experienced gynecologic oncologist and retired professoratNTNU.

AlekseiOgarkov,MDCoauthorDepartmentofRadiology and Nuclear Medicine, St Olav’s hospital, Trondheim UniversityHospital.AlekseiOgarkovisanexperienced radiologistandnuclearmedicinephysician.

EllenVeronikaVesterfjell,MDCoauthorDepartmentof Pathology, St Olav’s hospital, Trondheim University Hospital,7006Trondheim.EllenVeronikaVesterfjellis anexperiencedpathologistingynecologiconcology.

ØyvindSalvesen,PhDCoauthorUnitofAppliedClinical Research, Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian UniversityofScienceandTechnology.ØyvindSalvesen isastatisticianandanassociateprofessoratNTNU.

GuroAune,MDPhDCoauthorSectionofGynecologic Oncology,Dept.ofObstetricsandGynecology,StOlav’s hospital,TrondheimUniversityHospital.GuroAuneisan experienced gynecologist under sub specialization in gynecologic oncology.Sheis anassociateprofessorat NTNUandthemainsupervisorforthePhDworkofdr Nordskar.