Prostate cancer before renal

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Progrèsenurologie(2017)27,166—175

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ORIGINAL ARTICLE

Prostate cancer before renal

transplantation: A multicentre study

Cancer de prostate avant transplantation rénale : étude multicentrique

C. Chahwan

^a^,^k^,^l

, A. Doerﬂer

^a

, N. Brichart

^b

, S. Bouyé

^c

, T. Culty

^d

, C. Iselin

^e

, C. Pﬁster

^f

, F. Sallusto

^g

,

L. Salomon

^h

, G. Verhoest

ⁱ

, L. Viart

^j

, X. Tillou

^a^,^k^,^l^,∗

, the members of the Renal Transplantation Committee of the French Urological Association (CTAFU)

aUrologyandTransplantationdepartment,CHUCôte-de-Nacre,Caen,France

bUrologyandTransplantationdepartment,CHUdeTours,Tours,France

cUrologyandTransplantationdepartment,CHRUdeLille,Lille,France

dUrologyandTransplantationdepartment,CHUd’Angers,Angers,France

eUrologyandTransplantationdepartment,hôpitauxuniversitairedeGenève,Genève, Switzerland

fUrologyandTransplantationdepartment,CHUdeRouen,Rouen,France

gUrologyandTransplantationdepartment,CHUdeToulouse,Toulouse,France

hUrologyandTransplantationdepartment,CHUHenri-Mondor,Créteil—Paris,France

iUrologyandTransplantationdepartment,CHUdeRennes,Rennes,France

jUrologyandTransplantationdepartment,CHUd’Amiens,Amiens,France

kNormandieUniv,France

lUNICAEN,Caen,France

Received8August2016;accepted24January2017 Availableonline23February2017

KEYWORDS Prostaticneoplasms;

Kidney

transplantation

Summary

Introduction.—Thesurgicalissuesofrenaltransplantation(RT)afterlocalizedprostatecancer (PC)treatmentandoncologicaloutcomesaftertransplantationinpatientsonthewaitinglist withahistoryofPCwereunknown.Weconductedaretrospectivemulticentrestudyincluding allpatientswithPCdiagnosedbeforethekidneytransplantation.

∗Correspondingauthor.UrologyandTransplantationdepartment,CHUCôte-de-Nacre,avenuedeCôte-de-Nacre,14033Caen,France.

E-mailaddress:xavtillou@gmail.com(X.Tillou).

http://dx.doi.org/10.1016/j.purol.2017.01.001

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Prostatecancerbeforerenaltransplantation:Amulticentrestudy 167 Methods.—Fifty-two patients were included from December 1993 to December 2015. The medianageatdiagnosisofPCwas59.8yearsold.

Results.—ThemedianPSArateatdiagnosiswas7ng/mL.Twenty-seven,Twenty-four,andone PCwererespectivelylow,intermediateandhighriskaccordingtod’Amicoclassiﬁcation.Forty- threepatientsweretreatedbyradicalprostatectomy(RP):28retropubic,15laparoscopicand 3byaperinealapproach.Eighteenpatientshadalymphnodedissection.Fourpatientswere treatedwithexternalradiotherapyand2bybrachytherapy.Eightpatientsunderwentradio- therapyaftersurgery.ThemediantimebetweenPCtreatmentandRTwas35.7months.The medianoperatingtimefortherenaltransplantationwas180min(IQR150—190;min90—max 310)withamedianintraoperativebleedingof200mL(IQR100—290;min50—max2000).Ahis- toryoflymphadenectomydidnotsigniﬁcantlylengthenoperativetime(P=0.34).Norecurrence ofPCwasobservedafteramedianfollowof36months.

Conclusion.—PCdiscoveredbeforeRTshouldbetreatedwithRPtoassesstheriskofrecurrence anddecreasewaitingforaRT.IfthePCisatlowriskofrecurrence,itseemspossibletoshorten thewaitingtimebeforetheRTafteramultidisciplinarydiscussionmeeting.

Levelofevidence.— 4.

MOTSCLÉS Cancerdeprostate; Transplantation rénale

Résumé

Introduction.—Lesdifﬁcultéschirurgicalesdelatransplantationrénale(TR)aprèstraitement d’uncancerdelaprostatelocalisé(CP)etlesrésultatsoncologiquesaprèslatransplantation sontmalconnus.Nousavonsmenéuneétudemulticentriquerétrospectiveincluanttousles patientsatteintsdeCPdiagnostiquésavantlatransplantationrénale.

Méthodes.—Cinquante-deuxpatients ontétéinclusrétrospectivementde décembre1993à décembre2015.L’âgemédianaudiagnosticdeCPétaitde59,8ans.

Résultats.—LetauxdePSAmédianaudiagnosticétaitde7ng/mL.Vingt-sept,Vingt-quatreet unCPontétérespectivementclassésfaible,intermédiaireetàrisqueélevéselonlaclassiﬁ- cationded’Amico.Quarante-troispatientsontététraitésparprostatectomieradicale(PR): 28voierétropubienne,15laparoscopiqueet3paruneapprochepérinéale.Dix-huitpatients onteuuncurageganglionnaire.Quatrepatientsontététraitésparradiothérapieexterneet 2parcuriethérapie.Huitpatientsonteuuneradiothérapieaprèslachirurgie.Ledélaimédian entreletraitementduCPetlaTRétaitde35,7mois.Letempsopératoiremédiandetrans- plantationrénaleaétéde180min(min90—max310)avecunsaignementmédiande200mL (min50—max2000).Unantécédentdecurageganglionnairen’apasstatistiquementallongéle tempsopératoire(p=0,34).AucunerécidivedeCPn’aétéobservéeaprèsunsuivimédiande 36mois.

Conclusion.—LecancerdeprostatedécouvertavantlaTRdoitêtretraitépréférentiellement parPRpourévaluerlerisquederécidiveetdiminuerl’attented’uneTR.SilePCestàfaible risquederécidive,ilsemblepossiblederaccourcirletempsd’attenteavantlaTR.

Niveaudepreuve.— 4.

Introduction

Renal transplantation is classically described as the best treatment of chronic renal insufﬁciency. Despite the use of new induction therapies by monoclonal antibodies and newimmunosuppressivetherapies,suchasmTORinhibitors, cancer risk among renal transplant recipients remains signiﬁcant.Theliteraturegivesevidencethatevenifaggres- sive forms of prostate cancer (PC) in renal transplant recipients (RTR) are not greater, incidence and rate of locallyinvasiveformswerehighercomparedtothegeneral

population[1].Diagnosesaremadeearlier,around60years ofage [1].Apre-transplantcheck-upis thus fundamental todetect a latent cancer.The AmericanSociety of Trans- plantation recommends PSA measurement in addition to digitalrectalexamination(DRE)inmenover45beforereg- istrationonthe waitinglist[2].This systematic screening leading to a diagnosis of PC as reported in the litera- ture means that only curative treatment will allow the potential recipient to join the waiting list [3,4]. Studies reported only the oncological results of PC management priortosolidorgantransplantation [5]or casesof radical

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168 C.Chahwanetal.

prostatectomy (RP) before renal transplantation [6]. A monocentric study reported oncological features of PC beforerenaltransplantation, thespecific surgicaldifficul- ties withthe iliac vesselsor the bladder dissection after radicalprostatectomyandpotentialsurgicalcomplications ofrenal transplantation afterRP [7].Ourstudy examined characteristicsofrecipientsandprostatecancerdiscovered during pre-renal transplantation check-ups. We also ana- lysedsurgicaldifficultiesofrenaltransplantationrelatedto PCtreatment(RP,lymphnodesdissectionorradiotherapy) andtheresultsofrenaltransplantationafterradicalprosta- tectomy.Theoncologicalfollow-up beforeandafterrenal transplantation were analysed, especially the time lapse betweenPCtreatmentandrenaltransplantationaccording tothed’AmicoPCclassification[8].

Methods

We performed a retrospective data analysis including all patientsdiagnosedwithaPCbeforerenaltransplantationin 10urologyandtransplantationdepartmentsacrossthecoun- try.Fifty-twopatientsweretreatedforaPCpriortorenal transplantationfromAugust2003toDecember2015.Thirty- ninePCwerediagnosedduringthepre-transplantcheck-up and11afterindividualscreening.Twopatientswerediag- nosedonchipanalysisaftertransurethralresection.

Following National recommendations, allcandidates to renal transplantation had systematic DRE and PSA mea- surementwhen older than50. PC wasdiagnosed because of an abnormalof DRE or an increase in PSA levelslead- ing to prostate ultrasound guided biopsies In all cases, inscription on the waiting list was allowed at least one year after the end of PC treatment if PSA levels were undetectable.Clinical,biological,pathologicalresultsand therapeuticmodalitieswerecollectedretrospectively.Sur- gical difficulties during renal transplantation were based retrospectivelyonthesurgicalreports. Statisticalanalysis wasperformed using Graphpad Prism5^® software usinga t-testfor quantitativevariablesandanon-parametrictest for qualitative variables. A P-value under 0.05 was con- sidered significant. For statistical analysis, we compared onlythegroupsofpatientstreatedbyopenprostatectomy, laparoscopicprostatectomyandradiotherapyduetothelow number of patients treated by a perineal prostatectomy orbrachytherapy.Dataabout patientstreatedby perineal prostatectomyandbrachytherapyweredirectlyfilledinthe tables.DatacollectionfollowedFrenchlegislationconcern- ingretrospective non-interventional studies (BioethicLaw nô2004-800dated6/08/2004modified15/03/2012).

Results

Prostate cancer

The median age at diagnosis of PC was 59.8years old [IQR(interquartilerange)55.5—65.5;min45.6—max72.9]

(Table1).The median PSA rate at diagnosis was 7ng/mL (IQ5—9;min—max3.6—25).27,24,and1PCwererespec- tivelylow,intermediateandhighriskaccordingtod’Amico classiﬁcation.Twelve patients(23%)had apalpabletumor

(T2).Mediannumberofpositivebiopsieswas3(IQR2—6;min 1—max12)amonganaverageof12(IQR12—22;min9—max 34) biopsies performed. Forty-six patients were treated by prostatectomy (RP): 28 by open, 15 laparoscopic and 3 by a perineal approach. Eighteen patients had lymph node dissection:13 open prostatectomies, 3 laparoscopic prostatectomies, oneperinealprostatectomy (lymphnode dissectionbyaminilaparotomyapproach) andonebefore externalbeamtherapy(lymphnodedissectionbyalaparo- scopicapproach).Fourpatientsweretreatedwithexternal beamradiationand2bybrachytherapy.AllPCwereprostate adenocarcinomas. The pathological ﬁndings are detailed in Table 1. Eight patients underwent radiotherapy after surgery: 5for positive marginsand 3for pT3a tumors. At thetimeofPCtreatment,22patientswereondialysisand among them 3 were on peritoneal dialysis. Median daily urineoutputwas500mL(IQR300—500;min0—max2000).

After surgery, 5 patients had positive margins treated by additional external beam radiotherapy. PSA rates before renal transplantation were all stable (Nadir for patients treatedbyradiotherapy)orundetectable(patientstreated by surgery). For patients treated by external beam ther- apyorbrachytherapy,medianPSAratewas0.39ng/mL(IQR 0.27—1.97;min—max0.2—3.6).

Renal transplantation

Forallthe recipients,it wasa ﬁrstrenaltransplantation.

Alldonorsweredeceasedorgandonors,whosemedianage was 66 (IQR 62—74; min 21—max 80) with a sex-ratio of 0.7(19menand27women).Themediandonors’creatinine ratewas70(IQR56—85;min33—max140)␮mol/Landthe mediandonors’BMIwas24(IQR22—27;min15—max42.3).

Themedianageattransplantationwas64.9(IQR59.7—70.6;

min 48.9—max 81). The median time lapse between PC treatmentandkidneytransplantationwas35.7months(IQR 25—58;min 9.7—max166.8).Renaltransplantation results by PC treatment groups are analysed in Table 2. There werenodifferencesbetweenpatients forageat thetime ofrenaltransplantationor timelapse betweenPCandRT.

Tenrecipients(19.2%)weretransplantedlessthan24months afterprostatectomyandamongthem4lessthan15months.

MediantimebetweenPCtreatmentandRTwasshorterfor patientwithlowd’Amicoriskthanpatientwithintermediate orhighd’Amicorisk:26.4vs.42.6monthswithastatistical difference(P=0.0025) (Fig.1).Therewerenodifferences betweengroupsforpost-transplantationcreatininelevelsat 1month,1year,andatmedianfollow-up.

Surgical complications during renal transplantation

Five patients had difﬁcult preoperative urethral catheter placements due to urethral strictures (Table 3). Three of themunderwentendoscopicprocedurespriortoRTforblad- dercatheterplacement.AFreudenbergmandrelwasused toplacethebladdercatheterfortwopatients.Onepatient neededasurgicalprocedurewithbladderopeningtotreat a complete urethro-vesical anastomosis sclerosis. Among thesepatients,3hadadailyurineoutputbelow300mLand fourweretreatedbyopenprostatectomy.Thelastpatient wastreatedbylaparoscopicprostatectomy.Thepatientwith

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Prostatecancerbeforerenaltransplantation:Amulticentrestudy169

Table1 Prostatecancercharacteristicsbytreatmentgroups.

Openapproach (n=28)

Laparoscopic approach(n=15)

Radiotherapy (n=4)

P Perinealapproach (n=3)

Brachytherapy(n=2)

Medianageatdiagnosis(yearsold)(IQR) (min—max)

58(55—65) (51—73)

60(57—66) (46—71)

65(59—77) (57—80)

0.67 Patient1:69.9yo Patient1:57.9yo Patient2:49yo Patient2:61.9yo Patient3:65.5yo

Diagnosiscircumstances

Individualscreening 4 4 0 3 0

Pre-transplantationscreening 23 11 3 0 2

Prostateresection 1 0 1 0 0

Mediantimeofdialysisbeforeprostate cancer(months)(IQR)(min—max)

Vascularaccess 35(22—47

(0.7—81)

38(26—58) (8.1—73)

19(7.4—50) (5.3—59)

Patient1:5.7min Patient2:80.6m Patient2:39.4min Patient1:49.2m Patient3:58.4min

Peritoneal 5—24.8

(17.2—31.9) (14.4—42.5)

2—28.9 (15.4—42.5) (15.4—42.5)

0 0 0

cTNM

T1c 20 13 2 Patient1 Patient1

T1b 2 0 1 0 0

T2 6 2 1 Patient2and3 Patient2

MedianPSA(ng/mL)(IQR)(min—max) 7.2(5.5—8.5) (4—20)

6.9(5—8.3) (4.4—14)

6.7(3.8—14) (3.6—15)

0.9 Patient1:11.5ng/mL Patient1:9ng/mL Patient2:5.9ng/mL Patient2:4.8ng/mL Patient3:25ng/mL

MedianPB+(IQR) (min—max)

3(2—5) (1—12)

3 (2—6)

6(5.3—6.8) (5—7)

0.1 Patient1:11.5ng/mL Patient1:9ng/mL

(1—17) Patient2:5.9ng/mL Patient2:4.8ng/mL

16(12—22) (10—34)

15(12—21) (10—22)

12(12—12) (12—12)

0.19 Patient3:25ng/mL

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170C.Chahwanetal.

Table1 (Continued)

Openapproach (n=28)

Laparoscopic approach(n=15)

Radiotherapy (n=4)

P Perinealapproach (n=3)

Brachytherapy(n=2)

MedianPB(IQR) (min—max) PBGleasonscore

3+2 2 2 0 Patient2

3+3 18 9 2 Patients1,2,3

2+4 2 0 0

3+4 5 2 2 Patient1

4+2 0 1 0

4+3 1 1 0

d’Amicorisk

Lowrisk 16 9 1 Patient2 0

Intermediaterisk 12 6 3 Patient1 2

High 0 0 0 Patient3 0

MedianBMI(IQR)(min—max)

25(23—27) (21—32)

26(24—28) (21—25)

23(21—25) (21—25)

0.17 Patient1:28.4kg/m² Patient1:22.9kg/m² Patient2:27.3kg/m² Patient2:28.1kg/m² Patient3:nodata

IQR:interquartilerange;NA:notapplicable;PB+:positiveprostatebiopsies.

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Prostatecancerbeforerenaltransplantation:Amulticentrestudy 171 Table2 Prostatecarcinomahistologicalresultsandrenaltransplantationresultsbytreatmentgroups.

Open approach (n=28)

Laparoscopic approach (n=15)

Radiotherapy (n=4)

P Perineal approach (n=3)

Brachytherapy (n=2)

Prostatecarcinoma stage

pT2a 8 2

pT2b 5 2 NA NA

pT2c 12 7 Patients1and

2

pT3a 3 3 Patient3

Lymphnode dissection

Lowrisk 6 1

Intermediaterisk 7 2 1 0

Highrisk Patient3

Positivemargin 4(14.3%) 1(6.7%) NA 0.6 0 NA

Gleasonscore

3+2 3 2

3+3 15 6 Patients2and

3

2+4 2 0

3+4 7 5 NA Patient1 NA

4+2 0 0

4+3 1 1

4+4 0 1

MedianageatRT (yearsold)(IQR) (min—max)

64(60—71) (49—76)

63(59—66) (53—75)

73(67—79) (65—81)

0.067 Patient1 67yo

Patient1 61.1yo Patient2

51yo

Patient2 67.4yo Patient3

69yo Mediantime

betweenPCand RT(months)(IQR) (min—max)

34(25—52) (9.7—167)

37(25—58) (11—95)

45(17—84) (14—92)

0.97 Patient1 67yo

Patient1 37.1min

Patient2 51yo

Patient2 70min Patient3

69yo Mediandonor

creatininelevel (␮mol/L)(IQR) (min—max)

66.5(56—82) (43—121)

80.5(59—89.7) (44—140)

72.5(61—80) (61—80)

Patient1 71

Patient1 85

Patient2 100

Patient2 33 Patient3

NS Medianrecipient

creatininelevelat 1month(␮mol/L) (IQR)

(min—max)

159(132—195) (115—536)

150(114—182) (93—250)

150(111—251) (111—271)

0.5 Patient1 100

Patient1 169

Patient2 100

NS

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172 C.Chahwanetal.

Table2 (Continued) Open approach (n=28)

Radiotherapy (n=4)

P Perineal approach (n=3)

Brachytherapy (n=2)

Medianrecipient creatininelevelat 1year(␮mol/L) (IQR)

(min—max)

137(117—167) (97—465)

133(109—146) (94—384)

121(113—145) (113—145)

0.62 Patient1 122

Patient1 160

Patient2 120

NS

24 14 NA 2 NA

Nbofpatientswith indectablePSAat lastfollow-up Medianfollow-up afterRT(months) (IQR)

(min—max)

27(13—51) (4.1—90)

37(18—53) (7.7—72)

25(16—44) (16—48)

0.88 Patient1 38.1min

Patient1 85.4min

Patient2 23.5min

Patient2 44.5min Patient3

45.9min NA:notapplicable;PB+:positiveprostatebiopsies.

thecomplete urethro-vesicalanastomosissclerosishadno diuresisfor 2yearspriortoRT.None ofthesepatientshad radiotherapy.Themedianoperatingtimefortherenaltrans- plantationwas180min(IQR150—190;min90—max310)with amedianintraoperativebleedingof200mL(IQR100—290;

min50—max2000).

A history of lymphadenectomy did not signiﬁcan- tly lengthen operative time (P=0.34) or relate to

post-transplantation symptomatic lymphocele (P=0.3), which occurred in 5 patients (9.4%). However, history of lymph node dissection increased blood vessel dissection difﬁcultiesduringRT(P=0.0024).In17patients(32.7%),the bladderdissectionwasdescribedasdifﬁcultonthesurgical report, leading to perform pyelo-ureteral anastomoses in 5 patients (P=0.03). History of prostate irradiation (as a treatment of PC or as additional treatment after

Table3 Renaltransplantationsurgicalcomplicationsbytreatmentgroups.

Open approach (n=28)

Radiotherapy (n=4)

P Perineal

approach (n=3)

Brachytherapy (n=2)

Vesselsdissectiondifﬁculties

Yes 12 4 0 0.18 Patient3

No 16 11 4 Patient1

and2

Patient1and 2

Bladderdissectiondifﬁculties

Yes 10 5 1 0.9 Patient3

No 18 11 3 Patient1

and2

Patient1and 2

Surgicalcomplications

ClavienI 3 2 0

ClavienII 1 1 0

ClavienIIIa 3 0 1 NA

ClavienIIIb 8 3 1 Patient3

ClavienIVa 1 0 0

NA:notapplicable.

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Prostatecancerbeforerenaltransplantation:Amulticentrestudy 173

Figure1. Time between Prostate cancertreatment and renal transplantationbyd’Amicoriskgroup.

prostatectomy)didnotinﬂuencebladderdissectionduring RT(P=0.5).

Surgical complications after renal transplantation

Global rate of surgical complication after RT was 48%

(25/52): 13.5% (7/52) for Clavien 1 and 2 complications and 34.5% (18/52) for Calvien 3 and 4 complications.

Fourpatients(7.7%)hada postoperativeurinomabecause of uretero-vesical anastomosisleakage for 3 patients and uretere necrosis for one patient. These urinary ﬁstulas werenotrelatedtoresidualurinaryoutputvolume(P=1).

Two patients needed revision surgery (pyelo-urereteral anastomosis). One patient was treated by percutaneous nephrostomyandlengtheningofbladdercatheter.Thelast patient was treated by a solely lengthening of bladder catheterization. Novascular complications were reported even for patients with difﬁcult blood vessel dissection.

Threeof thesepatientshadadjuvant radiotherapy.Itwas not possible to distinguish arterial or venous dissection difﬁculties fromsurgical reports. One patienthad ipsilat- erallimbischemiafollowingadifﬁcultarterialanastomosis relatedtosevere arterial atherosclerosisand wastreated by percutaneousarterial stenting.History ofradiotherapy wasnotrelatedtosurgicalcomplicationsafterRT(P=0.2).

Post-transplantationsurgicalcomplicationsatleastClavien grade2werenotsigniﬁcantlyrelatedtodissectiondifﬁcul- ties(P=0.057).

Prostate cancer outcomes

Tworecurrences(3.8%)ofPCwereobserved60.4and28.5 monthsafterrenaltransplantationandrespectively91.1and

94.2 months after PC diagnosis. These recurrences were treated by radiotherapy for the ﬁrst patient secondarily complicatedbygraftureterstenosis.Initially,theprostate cancerwasclassiﬁedpT2bN0M0 afteropen prostatectomy withaPSArateof7.74ng/mL.The otherpatientreceived a hormonotherapy for a metastatic disease. Initially this patientwastreatedbyopenprostatectomy-radiotherapyfor a pT3aN0R1 PC with a PSA rate of 6ng/mL. After transplantation,nodeath relatedtothe prostate cancer were reported.

Most patients received antithymoglobulin or basilix- imab as an induction treatment. Then, they received ciclosporin or tacrolimus associated with mycophenolate mofetilandsteroids.Becauseoflocalorinternationaldif- ferences in immunosuppressive protocols, various events after transplantation (molecule switch or withdrawal secondary to virus infections; metabolic complications) immunosuppressive regimens were very heterogeneous.

It was not possible to analyze their inﬂuence on post- transplantationresultsandprostatecanceroutcomes.

Discussion

Prostate cancer is the most common cancer in men, but representsthethirdleadingcauseofmortalityfromcancer diseaseafter lung and colo-rectalcancer in France.Rou- tine screening for PCis not currently recommended, but individual screening may be offered to patients who ask for[9].ThepresenceofaPCisarealchallengeinpatients awaiting transplantation because there are no speciﬁc recommendations for the treatment of these patients. In renaltransplantation, theprognosis is notonly due toPC butalsotoESRDinrelationtodialysismorbidity.Theroleof theurologististoprovideacureforthepatientbyallowing inclusiononthewaitinglistafterascertainingtheabsence ofdiseaserecurrence.Intheory,thisperiodisﬁveyearswith nobiochemicalrecurrence[10].Periodbasedondatafroma studyevaluatingtheriskofrecurrenceaftertransplantation at around 18% in patients who underwent prostatectomy beforeorgantransplantation. A total of 77patients were reportedwitha previously treated PCbut PSA levelsand Gleasongradeswerenotavailable.Inthisstudy,differences weremadeaccordingtothedifferentstagesofPC,whileval- idatednomogramsshowingthatthesurvivalofpatientsand theriskofrecurrenceisvariabledependingonthestageof thedisease.Prostatecancerdeathcorrelatedwithdisease stage(3%,7%and28%for stageI,II andIII,respectively).

Theauthorsconcludedthatmenwithahistoryofprostate cancerwholaterundergosolidorgantransplantationhavea lowbutrealriskofrecurrenceanddeath,andpatientswith stageIIIdiseaseshouldhaveatleasta5-yeardisease-free period before transplantation. Another study based on the Penn data registry [5] classiﬁed patients according to the stage of the disease and concluded that low-risk patientsmaybecandidatesfortransplantationafter2years without recurrence. However, some missing data such as theGleason scoreandPSAmake theﬁndingsof thestudy questionable.

Inamonocentrestudywith14patients,allpatientswere classiﬁedasintermediateorlowrisk[7].Nobiologicalrecur- rencewasfound,allowingtransplantationafteranaverage

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174 C.Chahwanetal.

3-yearwaitingperiod.Authorsassessedtheriskofbiochem- icalrecurrenceat10yearsapplyingtheMSKCCnomogram.

Itdidnotexceed3%intheworst caseandwas1to2%in othercases.Thisnomogramhasprovenitsreliabilityinother studiesonlargecohorts [11].Thenomogramseemsuseful becauseitallowsregistrationonthewaitinglistatanearlier stage.Radicalprostatectomyhasmadethedecisiontoput thepatientonthetransplantlisteasier.Insteadofrespec- tinganarbitrarydeadline,theanalysisofinitialPSAlevels, prostatebiopsy,histologicalanalysisoftheradical prosta- tectomyspecimenandpostoperativePSAlevelscanleadto adecisionfor eachpatientconcerningthewaitingtimeto beregisteredonatransplantlist[6,12].Activesurveillance wasnotproposedtopatientsofourseriesdespiteamajority oflowriskprostatecancers.Theissueistodecidewhether thepatientshouldbeputonthewaitinglistforrenaltrans- plantationduringactivesurveillanceorifadelayshouldbe appliedtoassessPSAratestabilityortowaitfor prostate biopsiesreassessment.Therearenostudiesnorrecommen- dationsrightnowtosupportthismanagementoption.

In our study, radical prostatectomy made renal trans- plantationmoredifficultin45%ofpatients(22/46)without compromisingthetransplantation itself.Fivepatientshad urethra-vesicalanastomosisstenosisdiscoveredatthetime of the renal transplantation. In case of prostate cancer history, for patients treated by prostatectomy or with a low daily urine output, low urinary tract exploration by cystoscopycouldpreventsurgical difficulties.Lymph node dissection performed during radical prostatectomy made dissectionof the external iliac axismore difficult. For17 patients,bladderdissectionwasdifficultanddidnotallow uretero-vesicalanastomosisleadingtopyelo-ureteralanastomosis.History ofradiation,long timeofanuria,bladder catheterplacementdifficulties anda low volumebladder (noticedduringrenaltransplantation) shouldmake discuss toperformapyelo-ureteralanastomosis.

Five recipients (9.6%) hada post-renal transplantation symptomaticlymphocele.Itsincidencevaries accordingto series,depending on the diagnostic method, from0.6 to 33%[13] and is comparabletoourseries. Although ithas neverbeendescribedintheliterature,thesesurgicalresults suggest that it is possible to perform living donor renal transplantation.Howeverevenmorethanusual,thesetrans- plantationsshouldbeperformedbyexperiencedoperators.

Six patients were treated by prostate irradiation (4 by external beam radiotherapy and 2 by brachytherapy).

In 5 of these patients, diagnosis was made during pre- transplantation check-up. Thus, this choice is surprising becausecancer monitoring isbased onPSA screeningand PSA Nadir is obtained after 2 years. The drawback of these therapies is to extend the monitoring time and to lengthen waiting time before renal transplantation.

More surprisingly was the choice of brachytherapy for patient requiring renal transplantation. European recom- mendationsallowbrachytherapyasanalternative therapy to external beam radiotherapy but not as ﬁrst intention [14].

The limits of our study are its retrospective and his- toricalcharacteristicsanddespitebeingthelargestcohort described,therelativesmallnumber ofpatients. Another limitofthisstudyistheanalysisofthesurgicaldifﬁculties basedonsurgicalreportswhichnotastandardizedmethod.

We arenotabletoanalyzeif surgicalcomplications after renaltransplantationwererelatedtograftsfromextended criteriadonors(ECD)or ifpatientsinintermediateor high risk of d’Amicoprostate cancer receivedECD’s graft.The rarecharacterofprostatecancerbeforekidneytransplanta- tionmakesitdifficulttodrawdefiniteconclusions.However, thisdataaddedtothosefromtheliteraturemakeusbelieve we can adapt waiting time after prostate cancer according to the d’Amico classification. Our three recurrences occurredin twointermediateandonehigh-riskpatient.It confirmsthat itis possibletotailorwaiting timeforeach patient according to PC characteristics. For low risk PC, waitingtimeshouldbeoneyear, twoyearsfor intermedi- ateriskPC,andfiveyearsforhighrisksofrecurrenceafter amultidisciplinarydiscussionmeeting.

Conclusion

Inconclusion,diagnosisofprostatecancerinpatientsunder- going renal transplantation suggests radical treatment in ordertocompletethetransplantationproject.The choice of surgicaltreatment isjustiﬁedbythe needtoknow the risk of recurrence of the prostate cancer, based in part on the study of the prostatectomy specimen. A low risk of recurrenceshouldindicateearlierentryonthe waiting listfortransplantationespeciallyifthewaitmaybealong one. Increasedsurgical difﬁcultiesduring renal transplan- tationassociatedwithprostatecancertreatment: bladder catheterplacement,dissectionofthevascularaxisorofthe bladder,didnotcompromisetheimplementationofatrans- plant. Althoughradical prostatectomycouldcausecritical surgicalproblemsduringtransplantation,itensuresthebest oncologicfollow-upbeforeandafterkidneytransplantation.

ForlowriskPC,waitingtimecouldbeoneyear,for inter- mediateriskPCtwoyears,andﬁveyearsforhigh risksof recurrenceafteramultidisciplinarydiscussion.

Acknowledgments

Dr Sylvie Collon and Channing Bates for correcting the manuscript.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

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