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ORIGINAL ARTICLE
Overall survival and oncological outcomes after partial nephrectomy and radical
nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR
Comparaison de la survie globale et des résultats oncologiques après nephrectomie partielle et radicale pour cancer du rein cT2a : une étude
internationale menée par le réseau francais de recherche sur le cancer du rein UroCRR
B. Reix
a,∗, J.-C. Bernhard
b, J.-J. Patard
c, P. Bigot
d, A. Villers
a, E. Suer
e, N.S. Vuong
b, G. Verhoest
f,
Q. Alimi
f, J.-B. Beauval
g, T. Benoit
g, F.-X. Nouhaud
h, C. Lenormand
h, N. Hamidi
e, J. Cai
i, M. Eto
j,
S. Larre
k, A. El Bakhri
k, G. Ploussard
l, A. Hung
i, N. Koutlidis
m, A. Schneider
m, J. Carrouget
d, S.
Droupy
n, S. Marchal
n, A. Doerfler
o, S. Seddik
o, T. Matsugasumi
i, X. Orsoni
p, A. Descazeaud
p, C. Pfister
h, K. Bensalah
f, M. Soulie
g, I. Gill
i,
V. Flamand
a, members of the Kidney Cancer group of the CCAFU
qaDepartmentofurology,universityhospitalofLille,Lille,France
bDepartmentofurology,universityhospitalofBordeaux,Bordeaux,France
cDepartmentofurology,universityhospitalofKremlinBicêtre,KremlinBicêtre,France
dDepartmentofurology,universityhospitalofAngers,Angers,France
∗Correspondingauthor.Serviced’urologie,hôpitalHuriez,CHRU deLille,rueMichel-Polonowski,59000Lille,France.
E-mailaddress:boris.Reix@gmail.com(B.Reix).
https://doi.org/10.1016/j.purol.2017.12.004
1166-7087/©2017ElsevierMassonSAS.Allrightsreserved.
eDepartmentofurology,universityhospitalofAnkara,Ankara,Turkey
fDepartmentofurology,universityhospitalofRennes,Rennes,France
gDepartmentofurology,universityhospitalofToulouse,Toulouse,France
hDepartmentofurology,universityhospitalofRouen,Rouen,France
iUSCinstituteofurology,universityofSouthernCalifornia,LosAngeles,UnitedStates
jDepartmentofurology,universityhospitalofKumamoto,Kumamoto,Japan
kDepartmentofurology,universityhospitalofReims,Reims,France
lDepartmentofurology,universityhospitalofSaint-Louis,Paris,France
mDepartmentofurology,universityhospitalofDijon,Dijon,France
nDepartmentofurology,universityhospitalofNimes,Nimes,France
oDepartmentofurology,universityhospitalofCaen,Caen,France
pDepartmentofurology,universityhospitalofLimoges,Limoges,France
qParis,France
Received26July2017;accepted7December2017 Availableonline11January2018
KEYWORDS Oncology;
Outcomes;
Renalcancer;
Partialnephrectomy;
Sparingsurgery
Summary
Background.—Partialnephrectomy(PN)isrecommendedasfirst-linetreatmentforcT1stage kidneytumorsbecauseofabetterrenalfunctionandprobablyabetteroverallsurvivalthan radicalnephrectomy(RN). Forlargertumors,PNhasacontroversialpositionduetolack of evidenceshowinggoodcancercontrol.TheaimofthisstudywastocomparetheresultsofPN andRNincT2astageonoverallsurvivalandoncologicalresults.
Method.—A retrospective international multicenter study was conducted in the frame of theFrenchkidney cancer researchnetwork(UroCCR).Weconsideredall patients aged≥18 yearswhounderwentsurgicaltreatmentforlocalizedrenalcellcarcinoma(RCC)stagecT2a (7.1—10cm) between2000and2014.CoxandFine-Graymodels wereperformedtoanalyze overallsurvival(OS),cancerspecificsurvival(CSS)andcancer-freesurvival(CFS).Comparison betweenPNandRNwasrealizedafteranadjustmentbypropensityscoreconsideringprede- finedconfoundingfactors:age,sex,tumorsize,pTstageoftheTNMclassification,histological type,ISUPgrade,ASAscore.
Results.—Atotalof267patientswereincluded.OSat3and5yearswas93.6%and78.7%after PNand88.0%and76.2%afterRN,respectively.CSSat3and5yearswas95.4%and80.2%after PNand91.0%and85.0%after RN.Nosignificantdifferencebetweengroupswasfound after propensityscoreadjustmentforOS(HR0.87,95%CI:0.37—2.05,P=0.75),CSS(HR0.52,95%
CI:0.18—1.54,P=0.24)andCFS(HR1.02,95%CI:0.50—2.09,P=0.96).
Conclusion.—PNseemsequivalenttoRNforOS,CSSandCFSincT2astagekidneytumors.The riskofrecurrenceisprobablymorerelatedtoprognosticfactorsthanthesurgicaltechnique.
ThedecisiontoperformaPNshoulddependontechnical feasibilityratherthantumorsize, bothtoimperativeandelectivesituation.
Levelofevidence.— 4.
©2017ElsevierMassonSAS.Allrightsreserved.
MOTSCLÉS Cancerdurein; Néphrectomie partielle; Résultats oncologiques; Survieglobale
Résumé
Contexte.—Lanéphrectomiepartielle(NP)estrecommandéeenpremièreintentionpourles tumeursdureindestadescT1.SaplaceestdébattuepourlesstadescT2enraisondumanque depreuved’unboncontrôlecarcinologique.L’objectifdecetteétudeétaitdecomparerles résultatsdelaNPetdelanéphrectomieélargie(NE)danslesstadescT2asurlasurvieglobale etlesrésultatsoncologiques.
Méthode.—Une étude rétrospective multicentriqueinternationale était menée à partir de basesdedonnéesde15centres.Touslespatientsd’âge≥18ansayantbénéficiéd’untraitement chirurgicalpourunCCRlocalisédestadecT2a(7,1—10cm)entre2000et2014étaientinclus.
LacomparaisonentreNPetNEétaiteffectuéeaprèsajustementparscoreASAetparscore depropensiontenantcomptedesfacteursdeconfusionprédéfinis:âge,sexe,tailletumorale, stadepTdelaclassificationTNM,typehistologique,gradeISUP.
Résultats.—Autotal,267patientsétaientinclus.Lasurvieglobale(SG)à3et5ansétaitde 93,6%et78,7%danslegroupeNPetde88,0%et76,2%danslegroupeNE.Lasurviespécifique (SSp)à3et5ansétait de95,4%et80,2%danslegroupe NPetde91,0%et85,0%dans legroupeNE.Aucunedifférencesignificativeentrelesdeuxgroupesn’étaitretrouvéeaprès ajustementsurlescoredepropensionpourlaSG(HR0,87,IC0,37—2,05,p=0,75),laSSp(HR 0,52,IC0,18—1,54,p=0,24)etlaSurviesansrécidive(SSR)(HR1,02,IC0,50—2,09,p=0,96).
Conclusion.—Les résultatsde la NP semblent équivalents àla NE pourla SG, la SSp etla SSR.Lerisquederécidivesembledavantageliéauxfacteurspronostiquesqu’àlatechnique chirurgicale.LadécisiondeNPdevraitdépendredesafaisabilitétechniqueplutôtquedela tailletumorale,aussibienensituationélectivequ’impérative.
Niveaudepreuve.— 4.
©2017ElsevierMassonSAS.Tousdroitsr´eserv´es.
Introduction
The aging of population and the expansion of abdominal imagingindevelopedcountriesresultedinanincreasedinci- denceofrenalcellcarcinoma(RCC),includingsmalltumors [1,2].Currentlymosttumorsarefortuitouslydiscoveredat alocalizedstage[1].
However, epidemiological studies showed that despite earliertreatment ofthesecancers,therewasnoimprove- ment in patients’ overall survival (OS) after surgical management[3].Survivalwouldbedependentonotherfac- torsthancancercontrol.Themainhypothesisisanincrease incardiovasculareventscausedbythedeteriorationofrenal functionafterakidneyloss[4—6].
Partial nephrectomy (PN) aims to preserve kidney nephronand seemsimproving OS[7—9]. AccordingPatard et al. [10], this benefit outweighs the increased peri- operativemorbidityduetoahighlytechnicalact.
Indications of PN were initially limited to imperatives cases: solitary functional kidney, chronic kidney disease (CKD),bilateralsynchronoustumors.Thenitwasextended toelectiveindicationsforthesmallsizemasses,whichhave lowriskofrecurrence.ThePNisnowthegoldstandardfor cT1tumorsofUICCTNMclassificationof2009(size<7cm) [11].
TheplaceofPNfortumorslargerthan7cm(cT2)remains debated.PNisrecommendedinimperativescasesifsurgery istechnicallyfeasible[11].
Manytechnicaladvanceshaveimprovedsurgicalresults onthenephronpreservation andperi-operativemorbidity.
ThequestionoftheinterestofPNinelectivesituationfor cT2stagetumorscanbeasked.
Severaldescriptivestudieshavedemonstratedthefeasi- bilityofPNforcT2tumors[12—15].Themajorcomplication rate between 11—15% of cases was acceptable [13—15].
Bigotetal.found significantimpairmentofrenalfunction inonly22%ofpatients[15].
Oncologicrisklimitsachievingapartialsurgeryforthese badprognosis tumors.These tumorsareoften aggressive, witha greaterproportionofhigh ISUPgradeanda riskof upstaging(stagepT3a)[10,16,17].However,recentpublica- tionsshowedequivalentoncologicresultsbetweenPNand RNfortreatmentofhighISUPgradeorpT3astage[18—20].
FewstudiescomparedPNandRNforcT2tumorswithdis- cordantresults[18—20].Jeldres etal.found an increased riskof5.3timesofcancerdeathinthePNgroupcompared
RNgroup[18].Hansenetal.didnotfindsignificantdiffer- ences in cancerspecific survival (CSS)[19]. These studies includedoldcasesanddidnotfullyreflectmodernpractices ofpartialkidneysurgery.
Morerecently,Shumetal.foundabetterOSforPNthan RNfortumors>7cm(HR:5.3),butdonotstudyoncological results[21].
Wehypothesized that tumorsize>7cm wasnota con- traindicationforPN.
Themain objectiveofthisstudywastocompareOSin patientstreatedsurgicallybyRNorPNforcT2astagerenal cellcarcinoma(7.1—10cm).Secondary objectiveswereto assessCSSandcancerfreesurvival(CFS).
Materials and methods Data collection
Data source
Data were obtained from retrospective bases of patients treatedforrenaltumoratanystageofthedisease.Itwasan internationalmulticenterstudyinvolving fifteenuniversity centers:
• twelveFrenchcentersthatarepartof UroCCR(Angers, Bordeaux,Caen,Dijon,Lille,Limoges,Nimes,ParisSaint- Louis,Reims,Rennes,RouenandToulouse);
• oneAmericancenter(UniversityofSouthernCalifornia);
• oneJapaneseCenter(Kumamoto);
• oneTurkishCenter(Ankara).
Alldatabaseswerereportedtotherespectiveethicscom- mittees.
Study population
Allpatientswhounderwentsurgicaltreatmentforalocal- izedrenalcancercT2astage,between1January2000and 31December2014,wereincluded.
The treatment was a laparoscopic RN, an open PN or a laparoscopicPN. Thetherapeutic decision wastaken by thesurgeonandvalidatedinmulti-disciplinaryconsultation meeting.
ThecT2astagewasdefinedaccordingtothe7thedition of the2010 TNMClassification bytumor sizebetween 7.1 and10centimetersinlongaxisonpreoperativeimaging(CT scanorMRI).
Exclusioncriteriawere:
• age<18years;
• benigntumors;
• notprimarytumorsofthekidney;
• cancersassociatedwithgeneticdefects;
• pT≥3bstages;
• patientsN+orM+onthestagingorfinalhistologicalanal- ysis.
Variables collected
Clinicalanddemographicdata
Age, gender, ECOG performance status and the American societyofanesthesiologistsscore(ASA)werecollected.
Radiologicaldata
PreoperativeimagingspecifiedtumorsizeandRENALscore [22].
Surgicaldata
Partial or radical nephrectomy, and the approach, open orpurelaparoscopyor laparoscopywithroboticassistance werenotified.Incaseofpartialnephrectomy,elective(ePN) orimperative (iPN)indicationwasspecifiedandthecause for iPN: single kidney, bilateral tumors, CKD (estimated GFR<60mL/min/1,73m2).
Histologicaldata
Thepathologicalrecordshowedhistologicaltypeaccording toWHOclassificationof2004,ISUPgrade,pTNMstage,inva- sionoftheresectionmargins,microvascularinvasion,tumor necrosisor sarcomatoïdecomponent. LowISUP gradewas definedasgrade1or2andhighISUPgradewasdefinedas grade3or4.
IncaseofpT3astage,causeofupstagingwasfilled:inva- sionofrenalfatorperi-sinusalfat,tumoralthrombusinthe renalveinoroneofitsbranch.
Monitoringprotocols
MonitoringwascarriedoutbyCTscanor MRIofthechest, abdomenand pelvisat3 or 6monthsof surgeryandthen accordingtoeachcase.
Monitoringdata
Durationwasdefinedasthetimebetweensurgerydateand dateofthelatestnews.Death,relatedtocancerornotand localormetastaticrecurrencewerespecifiedafteranalysis ofmedicalrecords.
Statistical analysis
Qualitative parameters were described in terms of fre- quency and percentage. Numerical parameters were describedintermsofmean,medianandinterquartilerange (IQR). Normality of numerical parameters was checked graphicallyandtestedusingtheShapiro—Wilktest.
Comparisons between PN and RN on patients’ charac- teristicswereperformedusingtheChi−2test ortheFisher exacttest forcategoricalvariables,the Studentt test(or Mann—WhitneyUfornon-Gaussian distribution)forcontin- uous variables and the Mantel—Haenszel test for ordinal variables.
OSandPFSwere estimatedandcomparedbetween PN and RN using the Kaplan—Meier and log-rank test. Com- parisons were adjusted using a Cox model for predefined
confoundingfactorsselected apriorionthebasis oftheir potentialrelationshipswithsurvival:age,gender,histolog- icaltype,tumor size,stagepTof TNMclassification,ISUP grade and ASA score. Given the sample size, the adjust- mentwasdonebyincludingapropensityscoreasacovariate intheCox model.Propensityscore wasestimated usinga multivariatelogisticregressionmodelwiththegroupsasa dependentvariableandpotentialconfoundersascovariates.
ASAscorewasnotincludedinthecalculationofpropensity scorebecauseofalargenumberofmissingdata(23%).To minimizeconfoundingbias,asensitivityanalysiswasmade byincludingthe ASA scorein theCox model adjusted for propensityscore.
Thecumulativeincidenceofcancerrecurrencewasesti- matedandcomparedbetweenthetwogroupsusingamodel consideringcompetitiveriskdeathwithoutrecurrenceasa competitiveevent.Thecumulativeincidenceofrecurrence ofkidneycancerwasestimatedusingKalbfleischandPren- tice’sapproachandthecomparisonwasmadeusingtheGray test.WeusedtheFine—Grayregressionmodeltoadjustthe differencebetweenthegroupsonthepropensityscoreand ASAscore.UsingtheCoxandFine—GraymodelswithPNas thereferencegroup,wefoundhazardratio(HR),sub-hazard ratio(SHR),sizeof measuredeffect,andtheirconfidence interval95%.
Significancelevelwassetat5%.Statisticalanalyzeswere performedusingSASsoftware(SASinstituteversion9.4).
Results
Population characteristics
Total population
Atotalof267patientsunderwentsurgicaltreatmentforRCC cT2astage.
Medianage was62years([IQR]: 51—70), sexratiowas approximatelyonewomanfortwomen,52.2%(n=132)were asymptomatic tumors.ASA score was≥3at 17.0% (n=35) andECOGscore≥1in31.7%(n=58)ofpatients.
RNwasperformedin66%ofcases(n=176)andPNin34%
(n=91).
PNwasperformedforelectiveindicationin63%(n=57) and imperative in 37% (n=34). The reason of iPN was bilateraltumors (37.5%,n=12), solitaryfunctional kidney (43.8%,n=14)orchronicrenalfailure(18.8%,n=6).
RNwereperformedbyroboticlaparoscopy(8.5%,n=15) orconventionallaparoscopy(91.5%,n=161).PNwereper- formedbyopensurgery(67.0%,n=61),roboticlaparoscopy (26.4%,n=24)andconventionallaparoscopy(6.6%,n=6).
ApT3astagewasfoundin42.0%ofcases(n=112)anda highISUPgrade(3or4)in60.2%(n=157)(Tables1and2).
Comparison of radical nephrectomy (RN) and partial nephrectomy (PN) groups
There was no significant difference between RN and PN groupsforage(P=0.46),sex(P=1.00),tumorsize(P=0.38), ASAscore(P=0.63),andECOGPS(P=0.74).
TumorsremovedbyRNweremorelikelytobeclearcell carcinomas(P<0.01), pT3a stage (P<0.01) and high ISUP grade(P<0.001)(Tables1and2).
Table1 Clinicaldata.
Total RN PN Pvalue
Patients,n(%) 267 176(65.9) 91(34.1)
Age,years
Mean±SD 60.1±62(51—70) 60.5(63) 59.4(62) 0.458
Median(IQR) 51—71 50—68
Gender,n(%)
M 179(67.0) 118(67.1) 61(67.0) 0.998
F 88(33.0) 58(32.9) 30(33.0)
Symptomsatdiagnosis,n(%)
No 132(52.2) 75(44.6) 57(67.1) 0.003
Yes 121(47.8) 93(55.4) 28(32.9)
ASAscore,n(%)
≤2 171(83.0) 114(84.5) 57(80.3) 0.626
≥3 35(17.0) 21(15.5) 14(19.7)
ECOGPS,n(%)
0 125(68.3) 85(69.1) 40(66.7) 0.739
≥1 58(31.7) 38(30.9) 20(33.3)
Radiologicaltumorsize,cm
Mean±SD 8.40(8.0) 8.51(8.5) 8.17(8.0) 0.0006
Median(IQR) 8.0—9.0 8.0—9.0 7.0—9.0
RENALscore
≤8 81(44.0) 47(43.9) 34(44.2) 0.421
≥9 103(56.0) 60(56.1) 43(55.8)
Approach,n(%)
Open 61(22.9) 0 61(67.0)
Purelaparoscopy 167(62.5) 161(91.5) 6(6.6)
Robotassisted 39(14.6) 15(8.5) 24(26.4)
IndicationofPN,n(%)
ePN 57(62.6)
iPN 34(37.4)
IndicationifiPN,n(%)
Bilateraltumors 12(37.5)
Solitarykidney 14(43.75)
Chronickidneydisease 6(18.75)
RN:radicalnephrectomy;PN:partialnephrectomy;ePN:electivepartialnephrectomy;iPN:imperativepartialnephrectomy.
Comparison of elective partial nephrectomy (ePN) and imperative partial nephrectomy (iPN) groups
InthePNgroup,patientswhohadanimperativeindication wereolder(P=0.002)andhadahigherASAscore(P=0.021) andECOGscore(P=0.036).Positivemargin,pT3astage,and highISUP grade weremorefrequent in iPNgroup butnot significantly(Table3).
Comparison of results by type of surgery
Overall Survival
After a median follow up of 24 months (IQR: 12—43), 28 patientsdied(10.49%).
OSat3and5yearswere93.6%and78.7%inthePNgroup and88.0%and76.2%intheRNgroup,respectively(Fig.1A).
Afteradjustingforpropensityscore,nosignificantdiffer- encewasfoundbetweenthetwogroups (HR0.87,95%CI:
0.37—2.05,P=0.75),evenafteradjustmentforpropensity scoreandASAscore(HR0.85,95%CI:0.30—2.45,P=0.76).
Onedeathfrom anycause (1.8%) wasreportedin ePN groupand8(23.5%)iniPNgroup(Fig.1B).
Cancer specific survival
Therewere17deaths(6.4%)relatedtocancer.
CSSat3and5yearswere95.4%and80.2%inthePNgroup and91.0%and85.0%intheRNgroup,respectively(Fig.2A).
Afteradjustingforpropensityscore,nosignificantdiffer- encewasfoundbetweenthetwogroups(HR0.52,95%CI:
0.18—1.54,P=0.24),evenafteradjustmentforthepropen- sity score and ASA score (HR 0.40, 95% CI: 0.12—1.41, P=0.15).
Wenotedonecancerdeath(1.8%)intheePNgroupand 5(14.7%)intheiPNgroup(Fig.2B).
Cancer free survival
Fiftypatients(18.7%)hadalocalormetastaticrecurrence (Fig.3A).
InPN group, witha median follow-up of27 months, a recurrenceoccurredin13.2%ofpatients(n=12)atamedian
Table2 Histologicaldata.
Total(n=267) RN(n=176) PN(n=91) Pvalue Histologicaltumoralsize,cm
Mean(median) 8.2(8.0) 8.3(8.0) 8.0(8.0) 0.378
IQR 7.5—9.0 7.5—9.0 7.5—9.0
Histology,n(%)
Clearcell 198(74.2) 141(80.1) 57(62.6) 0.002
Papillary,typeI 21(7.9) 8(4.6) 13(14.3)
Papillary,typeII 8(3.0) 3(1.7) 5(5.5)
Chromophobe 26(9.7) 16(9.1) 10(11.0)
Others 14(5.2) 8(4.6) 6(6,6)
ISUPgrade,n(%)
Lowgrade,≤2 104(39.9) 57(32.8) 47(54.0) 0.0008
Highgrade,≥3 157(60.2) 117(67.2) 40(46.0)
pTstage,n(%)
pT1b 23(8.6) 19(10.8) 4(4.4) 0.008
pT2a 130(48.7) 71(40.3) 59(64.8)
pT2b 2(0.7) 2(1.1) 0
pT3a 112(42.0) 84(47.7) 28(30.8)
Peri-renalfatinvasion,n(%)
Yes 72(27.0) 49(27.8) 23(25.3) 0.654
No 195(73.0) 127(72.2) 68(74.7)
Sinusalfatinvasion,n(%)
Yes 54(22.5) 46(29.5) 8(9.5) 0.0004
No 186(77.5) 110(70.5) 76(90.5)
Tumorthrombusintherenalvein,n(%)
Yes 26(10.2) 24(14.0) 2(2.4) 0.004
No 229(89.8) 147(86.0) 82(97.6)
Microvascularinvasion,n(%)
Yes 52(22.5) 43(27.9) 9(11.7) 0.005
No 179(77.5) 111(72.1) 68(88.3)
Tumornecrosis,n(%)
Yes 104(47.3) 77(49.7) 27(41.5) 0.270
No 116(52.7) 78(50.3) 38(58.5)
Sarcomatoïdcomponent,n(%)
Yes 12(4.8) 10(6.0) 2(2.5) 0.347
No 236(95.2) 157(94.0) 79(97.5)
Positivesurgicalmargins,n(%)
Yes 11(4.7) 3(2.1) 8(8.9) 0.024
No 225(95.3) 143(97.9) 82(91.1)
RN:radicalnephrectomy;PN:partialnephrectomy.
timeof23months(IQR:12—48).1.0%(n=1)hadonlylocal recurrence,3.3%(n=3)hadlocalandmetastaticrecurrence and8.8%(n=8)hadmetastaticrecurrence.
In RN group, with a median follow-up of 23 month, a recurrenceoccurredin21.6%ofpatients(n=38)atamedian timeof19months(IQR:9.5—37).Atotalof1.1%(n=2)had onlylocalrecurrence,2.3%(n=4)hadlocalandmetastatic recurrenceand18,2%(n=32)patientshadmetastaticrecur- rence.
No significant difference was found between the two groups (HR 1.02, 95% CI: 0.50—2.09,P=0.96), even after adjustmentforthepropensityscoreandASAscore(HR0.52, 95%CI:0.23—1.21,P=0.13).
Recurrences occurredin10.5% ofePN(n=6)and17.6%
ofiPN(n=6)withamedianfollow-upof24and42months respectively(Fig.3B).
Discussion
PNandRNgiveidenticaloncologicalresultsinmanagement ofT1stagekidneytumors.PNseems,however,toprovide overall survival gain[7,8,23] withthe specific benefits of preserving nephron and decreasing cardiovascular events [5,9].CurrentrecommendationsstilladviseRNinfirstinten- tionfor patientshavingT2stageandnormalcontralateral kidney,orT3astagesuspectedtoimagingduetoatheoret- icalbettercancercontrol[11].
Despite a significant proportion of poor prognosis of tumorsinourcohort,theresultsofPNwereequivalentto RN for CSSand CFSfor cT2astage. Theseprognostic fac- torsweretakenintoaccountinouranalysisbyapropensity scoreadjustment.Ourresultsarein linewithrecentpub- licationsthatdonotputinevidencedifferenceforcancer
Table3 Clinical andpathologicalcharacteristics of patientsin thepartial nephrectomy(PN) group:elective partial nephrectomy(ePN)vsimperativepartialnephrectomy(iPN).
PN ePN iPN Pvalue
Patients,n 91 57(62.6) 34(37.4)
Ageinyears,mean(median) 59.4(62) 56.2(57) 64.7(65) 0.002
Gendern(%)
M 61(67.0) 36(61.8) 25(73.5) 0.309
F 30(33.0) 21(38.2) 9(26.5)
Symptomsatdiagnosis,n(%)
No 57(67.1) 40(72.7) 17(56.7) 0.320
Yes 28(32.9) 15(27.3) 13(43.3)
ASAscore,n(%)
≤2 57(80.3) 38(86.4) 19(70.4) 0.021
≥3 14(19.7) 6(13.6) 8(29.6)
ECOGPS,n(%)
0 40(66.7) 28(73.7) 12(54.6) 0.036
≥1 20(33.3) 10(26.3) 10(45.4)
Radiologicaltumorsizeincm,mean(median) 8.2(8.0) 8.1(8.0) 8.3(8.0) 0.102 RENALscore
≤8 34(44.16) 23(47.9) 2(11.8) 0.250
≥9 43(55.84) 25(52.1) 15(88.2)
Approach,n(%)
Open 61(67.0) 36(63.2) 25(73.5) 0.585
Classicallaparoscopy 6(6.6) 4(7.0) 2(5.9)
Robotassisted 24(26.4) 17(29.8) 7(20.6)
Histology,n(%)
Clearcell 57(62.6) 35(61.4) 22(64.7) 0.753
Others 34(37.4) 22(38.6) 12(35.3)
ISUPgrade,n(%)
Lowgrade,≤2 47(54.0) 34(63.0) 13(39.4) 0.078
Highgrade,≥3 40(46.0) 20(37.0) 20(60.6)
pTstage,n(%)
pT3a 28(30.8) 16(28.1) 12(35.3) 0.470
<pT3a 63(69.2) 41(81.9) 22(64.7)
Invasionofrenalfat,n(%)
Yes 23(25.3) 11(19.3) 12(35.3) 0.075
No 68(4.7) 46(80.7) 22(64.7)
Invasionofperi-sinusalfat,n(%)
Yes 8(9.5) 6(11.3) 2(6.5) 0.463
No 76(90.5) 47(88.7) 29(93.5)
Tumoralthrombusintherenalvein,n(%)
Yes 2(2.4) 2(3.8) 0(0,0) 0.274
No 82(97.6) 51(96.2) 31(100.0)
Microvascularinvasion,n(%)
Yes 9(11.7) 5(10.4) 4(13.8) 0.655
No 68(88.3) 43(89.6) 25(86.2)
Tumornecrosis,n(%)
Yes 27(41.5) 18(41.9) 9(40.9) 0.941
No 38(58.5) 25(58.1) 13(59.1)
Sarcomatoïdcomponent,n(%)
Yes 2(2.5) 0(0.0) 2(6.9) 0.055
No 79(97.5) 52(100.0) 27(93.1)
Positivesurgicalmargins,n(%)
Yes 8(8.9) 4(7.0) 4(12.1) 0.412
No 82(91.1) 53(93.0) 29(87.9)
PN:partialnephrectomy;ePN:electivepartialnephrectomy;iPN:imperativepartialnephrectomy.
Figure1. Overallsurvival. A.Partialnephrectomy(PN)vsrad- icalnephrectomy (RN).B.Electivepartialnephrectomy(ePN)vs imperativepartialnephrectomy(iPN)vsradicalnephrectomy(RN).
outcomesbetweenPNandRNfortumors>7cm,stagepT3a and high ISUP grade [18,19]. Jeldres et al. found inferi- ority of PN compared to RN on CSS for tumors>7cmbut thePNgroupincluded only17patients[18].Hansenetal.
didnotfindsignificantdifferencesinspecificsurvival(CSS) forpatientstreatedbetween1988and2008[19].Whatever typeofsurgery,cancercontrolwouldbeequivalentforcT2 stages.
WithaCSSat5yearsof80.2%forPNand85%forRN,our oncologicalresultswerebelowotherspublicationsanalyzing theT2stage,whichfoundCSSat5yearsbetween94.5and 98.1%forPN[14,15,18]and87.2%forRN[18].Nevertheless, our population hada higher rate of pT3a stage (42.0% vs 5.9to25%) andhigh ISUPgrade(60.2% vs17.6 to50.0%), whicharemajorprognosticfactors[14,15,18,19].Thisalso reflectsthecurrenttrendofwideningsurgicalindicationsin thetreatmentoflocallyadvancedrenaltumors.
In our study, we did not find significant difference betweenthe2groupsregardingOS.Thislackofsuperiority of PN could be explained by a relatively small monitor- ingperiod(median24months),whichfailedtohighlight a
Figure2. Cancerspecificsurvival.A.Partialnephrectomy(PN)vs radicalnephrectomy(RN).B.Electivepartialnephrectomy(ePN)vs imperativepartialnephrectomy(iPN)vsradicalnephrectomy(RN).
decreaseofcardiovasculareventsassociatedwithnephron preservation.Recently,Shumetal.foundabetterOSforPN thanRNfortumors>7cm(HR:5.3),withalargercohortand abetterglobalfollowupof49monthsbutrespectivefollow upineachgrouparenotdescribed[21].
Another explanation of our result for OS is the high proportionof imperative PN (37.4%), suggesting a poorer preoperative renal functionin the PN group compared to RNgroup.Dataonpreandpostoperativerenalfunctionand thepresenceofanormalcontralateralkidneywerenotreg- istered.
Several arguments limit the expansion of PN for cT2 tumors. First, importance of renal parenchyma resection may limit the nephron preservation. On this point, the results of PN for tumors>7cm seem close of PN for tumors<7cm.Longetal.andBigotetal.foundrespectively on 10.9% and 22% of patients a significantly worse renal functionafterPN.Carefulanalysisofpreoperativeimaging
Figure3. Cancerfreesurvival. A.Partialnephrectomy(PN) vs radicalnephrectomy(RN).B.Electivepartialnephrectomy(ePN)vs imperativepartialnephrectomy(iPN)vsradicalnephrectomy(RN).
and use of latest techniques of selective clamping, early unclampingandroboticsupporthave anyinterestinthese difficultcases.
Second,theriskofpositivemarginswouldbehigherthan for smaller tumors. Our rate of positive margins of 8.9%
byPNwascomparabletothosepublishedpreviously,rang- ingfrom10.2—11.2%[14,15].Thisrateissuperiortothose describedfor cT1stages (0to5.5%) [24].However,ithas been shown that the positivemargins do notsignificantly increasetheriskofrecurrence[24,25].Inourcohort,about 11casesofpositivemargins,3recurrencesoccurred,which shouldinduceincreasedsurveillanceforthesepatients.
Finally, risk of per and postoperative complications is higher. For tumors>7cm, complication rate is estimated between21.7%and48.8%,including10.9%—14.9%ofmajor
complications (DindoClavien≥3)[13,15]. Theserates are higherbutclosetoRN’sforT2stages,estimated between 28.7%and29.2%ofcomplications[26,27]including2.6%of majorcomplications[26].Furthermore,ithasbeenproved thattherateofcomplicationsinPNdecreasewiththesur- geon’sexperienceandadvancedsurgicaltechniques[28].
RegardingelectivePN(n=57),ourresultsweresatisfac- tory with10.5%of recurrences andonly onedeathduring follow-up. These patients were younger, withlow comor- bidities,buttheirtumorshadsamecharacteristics thanin imperative indications. This results has to be interpreted withcautionbecauseofashortmediumfollowupofonly24 monthsinePNgroupagainst42monthsiniPNgroup.
PN seems to have a place in the management of tumors>7cm,particularlyinelectiveindications,inyoung patients without comorbidities that can support a higher peri-operativemorbidityandgetthebenefitofthenephron preservation.Theriskofrecurrenceseemsmorerelatedto clinicalandpathologicalprognosticfactorsthanthesurgical technique.
We believe that tumor size should no longer be the decision-making criterion for the realization of a PN, but morethetechnicalfeasibilitywithcompletetumor resec- tion.SystematicevaluationofRENALscoreorPADUAscore couldhelpthesurgeon’schoice.
Ourstudyhasseveral limitations.Itsretrospective and non-randomized nature let to selection bias, with more aggressivetumorsintheRNgroupthaninthePNgroup.Our statisticalanalysisadjustingforpropensityscorehaslimited theseconfounders.Incaseofmultipletumors,pathological dataand treatment ofthe othertumors werenotknown.
Follow-up was relatively short but there is evidence that the majority of recurrences occur in the first years after treatment. The numbers of patientswere limitedbut our PN cohort is one of the most important in literature for tumors>7cm.Finally, this study hasincluded only expert centersanddonotrepresentallurologists’practices.
Prospective studies may provide a higher level of evidence but their implementation remains difficult for surgicaltreatments,especiallytothelowincidenceofnon- metastaticstagescT2.
Ourresultsleadtofurtherstudiesinlargernumbersand usingprospectivelyhelddatabases.
Conclusion
PNseemsequivalenttoRNforOS,CSSandCFSincT2astage kidneytumors.
Theriskofrecurrenceisprobablymorerelatedtoprog- nosticfactorsthansurgicaltechnique.
PN seems to have a place in the management of tumors>7cm, particularly in elective situation, in young patientswithoutcomorbidities.
ThedecisiontoperformaPNshoulddependontechnical feasibilityrather thantumor size,both in imperative and electivesituation.
Disclosure of interest
Theauthorshavenotsuppliedtheirdeclarationofcompet- inginterest.
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