C-Choline PET/CT and CT for Predicting Survival of Bladder Cancer Patients Treated with Radical Cystectomy

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1 Urologi Interntionlis Originl Pper DOI: 1.59/35766 Received: September 16, 213 Accepted fter revision: November 29, 213 Published online: July 9, 214 Prognostic Vlue of C-Choline PET/CT nd CT for Predicting Survivl of Bldder Cncer Ptients Treted with Rdicl Cystectomy Tobis Murer Thoms Horn Michel Souvtzoglou b Mtthis Eiber c Ambros J. Beer b Mtthis M. Heck Bernhrd Hller d Jürgen E. Gschwend Mrkus Schwiger b Uwe Treiber Bernd J. Kruse e Deprtment of Urology, b Deprtment of Nucler Medicine, c Deprtment of Rdiology nd d Institute of Medicl Sttistics nd Epidemiology, Technische Universität München, Klinikum rechts der Isr, Munich, nd e Deprtment of Nucler Medicine, University of Rostock, Rostock, Germny Key Words Bldder cncer Choline Positron emission tomogrphycomputed tomogrphy Cncer-specific deth Overll survivl Abstrct Bckground: In ptients with bldder cncer (BC) preopertive stging with C-choline positron emission tomogrphy-computed tomogrphy (PET/CT) could be used to derive prognostic informtion nd hence strtify ptients preopertively with respect to disese mngement. Methods: From June 24 to My 27, 44 ptients with loclized BC were stged with C-choline PET/CT before rdicl cystectomy. The results of imging were correlted to overll survivl (OS) nd cumultive incidence of cncerspecific deth (CSD). Results: There ws no sttisticlly significnt difference in OS nd CSD between the ptient groups when strtified for orgn-confined versus non-orgn-confined disese or lymph node involvement defined E-Mil krger@krger.com S. Krger AG, Bsel 42 3/14/ $39.5/ by either C-choline PET/CT (OS: p =.262, hzrd rtio [HR] = 1.6; p =.527, HR =.76; CSD: p =.144, HR = 2.25; p =.976, HR =.9) or CT (OS: p =.51, HR = 1.34; p =.22, HR = 1.67; CSD: p =.323, HR = 1.9; p =.136, HR = 2.3). The limittion of this study is the smll number of included ptients. Conclusion: In our prospective tril neither CT nor C-choline PET/CT were ble to sufficiently predict OS or CSD in BC ptients treted with rdicl cystectomy lbeit trends nd modertely incresed HRs could be demonstrted without significnt differences between CT or C-choline PET/CT. However, these trends might prove sttisticlly significnt in bigger ptient cohorts. Therefore initil trnssectionl imging might be of clinicl relevnce in respect to prognosis nd could ply role in the counseling of BC ptients. 214 S. Krger AG, Bsel T. Murer nd T. Horn contributed eqully to this work. Tobis Murer, MD Deprtment of Urology, Technische Universität München Klinikum rechts der Isr, Ismninger Strsse 22 DE 1671 München (Germny) E-Mil lrz.tum.de /1/214 7:2:52 AM

2 2 Introduction DOI: 1.59/35766 In Europe, pproximtely, cses of bldder cncer (BC) re newly dignosed ech yer nd the overll BC mortlity rte per yer rnges from 1.2 (for women) to 5.5 (for men) per 1, inhbitnts [1, 2]. At initil dignosis, bout 7% of ptients with BC present with non-muscle-invsive disese wheres 3% show muscle-invsive cncer [1]. Especilly muscle-invsive BC (MIBC) nd high-risk non-muscle-invsive BC (NMIBC) represent n ggressive nd potentilly life-thretening disese requiring optiml tretment strtegies. The stndrd tretment for MIBC is rdicl cystectomy (RCX) with pelvic lymph node dissection (PLND) whose extent is currently still under discussion [1]. However, in loclly dvnced disese with high risk for development of metstses, pltinum-bsed neodjuvnt chemotherpy regimes improve cure rtes while pllitive tretment is dvocted for metsttic disese [3, 4]. Therefore, ccurte pre-tretment stging of ptients with high-risk BC or MIBC hs direct implictions on further mngement nd ptient outcome. Unfortuntely, current clinicl stging procedures (computed tomogrphy [CT] or mgnetic resonnce imging [MRI]) for BC re insufficient since upstging from orgn-confined (OC) lymph node-negtive BC to non-orgn-confined (NOC) BC or BC with lymph node metstses on finl pthology occurs in pproximtely 4% of ptients [1, 5, 6]. Severl risk fctors either leding to pthologicl upstging in BC ptients fter RCX nd PLND or compromising recurrence-free nd overll survivl (OS) rtes hve been estblished. These include presence of preopertive hydronephrosis, evidence of lymphovsculr invsion, deep musculris propri infiltrtion nd non-ppillry or solid tumor growth pttern in the histologicl specimen fter trnsurethrl resection s well s multiplicity of tumors nd ge of ptients [7 ]. Clinicl nomogrms incorporting these fctors hve been proposed to pre-therpeuticlly identify ptients in whom upstging is likely nd who might benefit from neodjuvnt regimens [1, ]. However, some uthors support the use of neodjuvnt chemotherpy even in ptients with cliniclly OC disese lso becuse upstged ptients on finl pthology fter RCX often do not receive djuvnt chemotherpy [12]. Recently, positron emission tomogrphy (PET) s functionl imging with trcers like 1 F-FDG, C-choline or C-cette in combintion with CT hs been introduced [13 26]. However, these studies present conflicting dt s to whether these new imging modlities re ble to improve clinicl stging in comprison to results of the gold stndrd histopthology. The ccurcy of this gold stndrd on the other hnd hevily depends on meticulous lymph node preprtion (omitting smpling error by incomplete dissection of lymphtic tissue) s well s subtle pthologicl evlution to identify even smll metsttic lesions especilly in norml-sized lymph nodes (omitting nlyticl error) nd might therefore be subject to bis, especilly when reporting lymph nodenegtive disese [27, 2]. Relevnt endpoints for the individul ptient, however, represent recurrence-free survivl, disese-specific survivl or OS fter potentilly curtive tretment endpoints tht my be difficult to ssess preopertively. To our knowledge, so fr there re only two studies correlting the results of pre-therpeutic PET/CT imging (both with 1 F-FDG) with survivl [13, 17]. Thus, the im of our study ws the definition of prognostic ccurcy of preopertive stging with C-choline PET/CT nd sole CT regrding OS nd cumultive incidence of cncerspecific deth (CSD) in comprison to histopthologicl evlution. Therefore we followed the ptients of our previously published prospective study, exmining the dignostic ccurcy of lymph node stging with C-choline PET/CT in comprison to sole CT nd histopthologicl evlution in ptients with BC treted with RCX nd PLND [23]. Ptients nd Methods Ptients After pprovl by the locl ethics committee nd obtining informed consent, 44 ptients with histologiclly proven highgrde or muscle-invsive loclized urothelil crcinom of the bldder underwent stndrdized RCX nd PLND within men of 13.5 dys (medin 6. dys, rnge 1 9 dys) fter C-choline PET/CT from June 24 to My 27 [23]. Ptients with metsttic disese were not included since they did not undergo surgery but pllitive tretment. All ptients received stndrd templte PLND up to the ortic bifurction. In 2 ptients with suspicion of loclly dvnced disese ( T3) or lymph node involvement (LN+) by imging, n extended PLND up to the origin of the inferior mesenteric rtery ws performed in ddition. Histopthologicl dignosis of locl BC nd the presence or bsence of lymph node metstses ws bsed on histologicl exmintion of surgicl specimens nd the TNM clssifiction system [29]. To minimize pthologicl understging nd to mximize histologicl lymph node yield, tissue from ech ntomicl Murer et l /1/214 7:2:52 AM

3 Tble 1. Three- nd 5-yer OS nd cumultive incidence of CSD for ptients with T2 N, T3 N or T1 4 N+ BC ccording to C- choline PET/CT, sole CT exmintion or postopertive histologicl evlution (estimted mens nd 95% CIs re presented) Ctegory n OSCSD 3 yers 5 yers 3 ye rs 5 yers C-choline PET/CT T2 N 1 67% (4 92) 61% (42 ) 22% (7 44) 22% (7 44) T3 N 3% (15 92) 3% (15 92) 3% (7 7) 3% (7 7) T1 4 N+ 1 61% (42 ) 5% (32 79) 2% (1 5) 33% (13 55) CT T2 N 13 69% (4 99) 62% (4 95) 15% (2 4) 15% (2 4) T3 N 9 7% (55 1) 67% (42 1) 22% (3 53) 22% (3 53) T1 4 N % (29 72) 41% (25 6) 36% (17 56) 41% (2 61) Histology T2 N 2 75% (5 97) 65% (47 9) 2% (6 4) 2% (6 4) T3 N 12 5% (2 ) 42% (21 1) 17% (2 43) 25% (5 52) T1 4 N % (21 1) 42% (21 1) 5% (19 75) 5% (19 75) field ws dissected seprtely by experienced uropthologists [27]. In totl, 19 ptients showed OC lymph node-negtive disese ( pt2 pn), 13 ptients presented with NOC lymph nodenegtive disese ( pt3 pn) nd 12 ptients with metsttic lymph node involvement (pt1 4 pn+) on finl histologicl evlution. Follow-up informtion from ech ptient ws obtined regulrly through contct of ptients nd primry physicins s well s through the locl tumor register (Tumorzentrum München). The medin follow-up ws 7.2 months (rnge 1 9 months). Imge Anlysis Imging ws performed s previously described [23]. Briefly, two independent bord-certified nucler medicine physicins who were lso bord-certified rdiologists nlyzed CT imges solely or C-choline PET/CT imges for evidence of NOC disese nd lymph node involvement. For determintion of NOC, thickening of the bldder wll, suspicion of infiltrtion of the prvesicl ft nd stndrd uptke vlues of C-choline were evluted. Bldder lesions were clssified s OC versus NOC ccording to findings on CT imges solely or C-choline PET/CT imges in consensus. For determintion of lymph node involvement, size, shpe nd contrst enhncement s well s foclly incresed, not physiologicl C-choline uptke ws evluted nd lesions were grded for CT lone or C-choline PET/CT ccording to grding system in consensus (1: metsttic infiltrtion; 2: probbly metsttic; 3: equivocl; 4: probbly benign; 5: benign). For correltion with histopthology, lesions scored 1 nd 2 were considered s positive for tumor, nd lesions scored 3, 4 nd 5 s negtive for tumor, s this hd proved to exhibit best discrimintory power in our initil report [23]. Sttisticl Anlysis The medin follow-up time ws determined by the Kpln- Meier estimte for potentil follow-up [3]. OS for relevnt groups ws determined by the Kpln-Meier method. Cumultive incidence of CSD, denoting the estimted probbility of CSD up to given time point, ws ssessed using the librry cmprsk [31] of the sttisticl softwre R version ccounting for Correltion of C-Choline PET/CT nd Survivl in Bldder Cncer deth from other cuses s competing risks. The log-rnk test ws performed to compre survivl curves nd cuse-specific hzrd rtes for CSD between groups. 95% confidence intervls (CIs) re presented for 3- nd 5-yer OS nd CSD. Additionlly, Cox regression ws pplied to estimte hzrd rtios (HRs) nd cusespecific HRs with 95% CIs. All sttisticl tests were performed on two-sided level of significnce of α = 5%. Results Estimted 5-yer OS probbilities for ptients with stge T2 N s clssified by C-choline PET/CT, sole CT exmintion or histology ws 61, 62 nd 65%, for ptients with T3 N 3, 67 nd 42%, nd for ptients with T1 4 N+ disese 5, 41 nd 42%, respectively. In totl, the estimted 5- nd 3-yer OS by C-choline PET/CT, sole CT or histology did not show relevnt differences for ptients dignosed within these groups ( tble 1 ). Also, no significnt differences could be observed when ptients were strtified for OC nd NOC disese irrespective of lymph node sttus ( fig. 1 c) or for lymph node involvement irrespective of T clssifiction ( fig. 1 d f). While C-choline PET/CT showed slightly superior p vlue nd HR concerning OS compred to CT (p =.262 vs. p =.51; HR = 1.6 vs. HR = 1.34) when strtifying for extent of locl bldder tumor (OC vs. NOC), sole CT exmintion demonstrted moderte improvement compred to C-choline PET/CT when strtifying for lymph node involvement (p =.22 vs. p =.527; HR = 1.67 vs. HR =.76). However, in our ptient cohort C-choline PET/CT s well s CT did not prove to be significnt predictor for OS. DOI: 1.59/ /1/214 7:2:52 AM

4 1.. PET/CT p = CT p = Histology p =.69 OC NOC OS HR: 1.6 ( ) HR: 1.34 ( ) b HR: 2.15 ( ) c p = p = p =.32 LN LN + OS d HR:.76 ( ) HR: 1.67 ( ) HR: 1.49 ( ) e f Time (yers) Time (yers) Time (yers) Fig. 1. OS of BC ptients with OC ( T2) versus NOC ( T3) disese nd of BC ptients with or without metsttic lymph node involvement (LN+ vs. LN ) s determined by C-choline PET/CT, sole CT exmintion or histopthologicl nlysis. p vlues of log-rnk tests s well s HRs of Cox regression nlysis with 95% CIs re shown. 4 DOI: 1.59/35766 Concerning cumultive incidence of CSD, estimted probbilities for C-choline PET/CT, sole CT exmintion or histology fter 5 yers were 22, 15 nd 2% for ptients with T2 N, 3, 22 nd 25% for ptients with T3 N, nd 33, 41 nd 5% for ptients with T1 4 N+ disese, respectively ( tble 1 ). For CSD, no significnt differences could be observed when ptients were strtified for OC nd NOC disese irrespective of lymph node sttus ( fig. 2 c) or for lymph node involvement irrespective of T clssifiction ( fig. 2 d f). Here, C-choline PET/CT showed lmost equl p vlues concerning CSD compred to CT (p =.144 vs. p =.323; HR = 2.25 vs. HR = 1.9) when strtifying for extent of locl bldder tumor (OC vs. NOC), while sole CT exmintion demonstrted n observble, yet insignificnt improvement compred to C-choline PET/CT when strtifying for lymph node involvement (p =.136 vs. p =.976; HR = 2.3 vs. HR =.9). Tken together, in our ptient cohort both imging modlities could not relibly identify ptients with incresed risk of CSD in contrst to postopertive histologicl nlysis. Not surprisingly, postopertive histologicl nlysis proved to be significnt predictor of CSD when ptients were strtified ccording to locl tumor (p =.42; HR = 3.19) or lymph node involvement (p =.36; HR = 3.5). Negtive results of C-choline PET/CT nd CT were found in 12 (27%) nd 14 (32%) ptients with histopthologiclly confirmed lymph node metstsis, nd suspicious findings on C-choline PET/CT nd CT were described in 5 (%) nd 3 (7%) ptients without lymph node involvement on histopthologicl nlysis. Postopertive ssessment of prognosis combining results of imging ( C-choline PET/CT or CT) nd histopthologicl evlution concerning lymph node sttus for ptients with positive findings on imging nd histologiclly confirmed lymph node metstses showed wek trend for worse OS (p =.7 vs. p =.166; HR = 1.25 vs. HR = 2.12), but pronounced tendency for higher CSD (p =.27 vs. p =.29; HR = 2.63 vs. HR = 4.94) compred to ptients with negtive findings on imging nd histologicl nlysis. However, the ptient groups were too smll to dequtely nlyze subgroups of ptients especilly subgroups with diverging results for imging nd histopthologicl nlysis. Murer et l /1/214 7:2:52 AM

5 1.. PET/CT p =.144 HR: 2.25 ( ) 1.. CT p =.323 HR: 1.9 ( ) 1.. Histology p =.42 HR: 3.19 ( ) OC NOC CSD b c p =.976 HR:.9 ( ) 1.. p =.136 HR: 2.3 ( ) 1.. p =.36 HR: 3.5 ( ) LN LN CSD d e f Time (yers) Time (yers) Time (yers) Fig. 2. Cumultive incidence of CSD of BC ptients with OC ( T2) versus NOC ( T3) disese nd of BC ptients with or without metsttic lymph node involvement (LN+ vs. LN ) s determined by C-choline PET/CT, sole CT exmintion or histopthologicl nlysis. p vlues of log-rnk tests s well s HRs of Cox regression nlysis with 95% CIs re shown. Discussion Correltion of C-Choline PET/CT nd Survivl in Bldder Cncer Cross-sectionl imging remins minsty in the stging nd the pre-therpeutic decision-mking process in ptients with extensive high-grde NMIBC or MIBC. The most widely used imging modlities, however, rely solely on morphology nd show ccurcy rtes for determintion of loclly dvnced ( T3) disese between 55 nd 92% (for CT) nd between 73 nd 96% (for MRI), with sensitivity rtes for detection of metsttic lymph nodes from 4 to 7% limited by low specificity rtes for both imging techniques [1]. Thus, upstging on finl pthology fter RCX nd PLND is common finding for both CT nd MRI [6, 32]. Especilly metsttic disese to the lymph nodes hs gret impct on prognosis, with lymph node density nd extrcpsulr extension rther thn size of the metsttic lesion representing the strongest prognostic fctors [33 36]. Over the lst few yers PET/CT with the trcers 1 F- FDG, C-choline or C-cette hs evolved s new stging modlity combining cross-sectionl ntomicl nd functionl imging [13 26]. Severl studies described incresed ccurcy nd high specificity rtes especilly in the detection of lymph nodes or distnt metstses to bone nd viscerl orgns with 1 F-FDG-bsed [13, 16, 17, 19, 2], Ccholine-bsed [14, 24, 37] or C-cette-bsed [24] PET/ CT, which hd n impct on further clinicl mngement in significnt number of ptients. Therefore, those uthors concluded tht PET/CT might hve the bility to replce stndrd cross-sectionl imging or bone scintigrphy in the stging of BC. This view is chllenged by others who could not observe significnt improvement, minly becuse of unspecific trcer uptke cused by inflmmtory chnges fter instilltion of immuno- or chemotherpeuticl gents or trnsurethrl resection [1, 22, 23, 25, 26]. In our ptient cohort, for exmple, we could not observe n improved dignostic efficcy of preopertive lymph node stging by C-choline PET/CT compred to conventionl CT lone either [23]. However, up to now, no finl conclusion on the vlue of PET/CT for stging of locl tumor, lymph node involvement nd distl orgns in BC ptients cn be drwn, minly since these dt re bsed on reltively smll nd in prt heterogeneous study cohorts. DOI: 1.59/ /1/214 7:2:52 AM

6 6 DOI: 1.59/35766 Furthermore, in most studies the performnce of imging is determined by comprison to the gold stndrd of postopertive histopthologicl evlution nd not directly to recurrence-free survivl, disese-specific survivl or OS, which represent relevnt endpoints for the individul ptient. So fr, only two studies correlted the results of 1 F- FDG PET/CT imging with time to recurrence, overll or disese-specific survivl [13, 17]. In the study by Drieskens et l. [13], 55 ptients with non-metsttic invsive BC were subjected to 1 F-FDG PET followed by CT within 14 dys. 32 ptients received curtive tretment consisting of RCX nd PLND lone or in combintion with either neodjuvnt or djuvnt chemo- or rdiotherpy, while 23 ptients were only treted with chemo- or rdiotherpy or did not receive ny tretment. The medin OS of ptients with positive findings on 1 F-FDG PET nd CT ws 13.5 months versus 32 months for ptients without suspicious results. However, only 42% (5/12) of ptients with positive 1 F- FDG PET nd CT received curtive tretment compred to 63% (27/43) of ptients with negtive findings, nd therefore the results hve to be considered with cution. Kibel et l. [17] reported on 42 BC ptients without loclly dvnced or metsttic disese on conventionl imging who underwent preopertive 1 F-FDG PET/CT before RCX nd PLND. One ptient with suspicion of metsttic disese on 1 F-FDG PET/CT did not undergo surgery, while nother ptient received neodjuvnt chemotherpy fter lymph node biopsy before RCX. In this homogenous ptient cohort the recurrence-free, overll nd disese-specific survivl t 24 months ws, 23 nd 23% for ptients with positive findings on preopertive 1 F-FDG PET/CT (n = 9), compred to 55, 62 nd 5% for ptients without evidence of lymph node metstses (n = 33). Therefore it ws concluded tht 1 F-FDG PET/CT yields high dignostic nd prognostic ccurcy tht might be useful in the decisionmking process nd selection of the pproprite tretment strtegy prior to RCX. Our study with 44 ptients ll treted with RCX nd PLND without prior neodjuvnt chemotherpy ws only ble to demonstrte non-significnt trends for C-choline PET/CT or CT lone in predicting OS or CSD in ptients with OC vs. NOC BC or LN+ versus LN disese with modertely incresed HRs for ptients with evidence of NOC in C-choline PET/CT or of NOC nd LN+ disese in CT. These t first glnce contrdictory findings cn t lest prtly be explined by the low number of included ptients in our prospective study s well s by the fct tht our study included ptients with less dvnced disese, since our survivl rtes re greter thn in the study by Kibel et l. [17]. Also, the fct tht 2 ptients with suspicion of loclly dvnced disese ( T3) or lymph node involvement by imging received more extended PLND up to the origin of the mesenteric rtery might hve influenced our findings. Additionlly, six ptients with newly dignosed metsttic disese (M+) by C-choline PET/CT (visible lso on sole CT exmintion) were not operted nd excluded from the initil study nd from further nlysis [23]. Although in our prospective tril neither CT nor C- choline PET/CT were ble to significntly predict ptients OS nd CSD, the potentil vlue of these preopertive imging modlities with respect to prognosis should be evluted in lrger ptient cohorts in the future since their results very well might hve n impct on ptient counseling. The development of BC-specific rdiophrmceuticl trcers is desirble to further improve dignostic stging nd the predictive vlue of PET-bsed imging. New imging modlities like combintion of PET nd MRI, however, could potentilly improve the dignostic nd prognostic vlue of preopertive imging [3]. Disclosure Sttement The uthors hve no conflict of interest. References 1 Stenzl A, Witjes JA, Compért E, Cown NC, De Sntis M, Kuczyk M, Lebret T, Ribl MJ, Sherif A: Guidelines on bldder cncer muscle-invsive nd metsttic. Edition presented t the 27th EAU Annul Congress, Pris, Bldder%2Cncer_LR%2II.pdf. 2 Bosetti C, Bertuccio P, Chtenoud L, Negri E, L Vecchi C, Levi F: Trends in mortlity from urologic cncers in Europe, Eur Urol 2; 6: Grossmn HB, Ntle RB, Tngen CM, Speights VO, Vogelzng NJ, Trump DL, devere White RW, Srosdy MF, Wood DP Jr, Rghvn D, Crwford ED: Neodjuvnt chemotherpy plus cystectomy compred with cystectomy lone for loclly dvnced bldder cncer. N Engl J Med 23; 349: Advnced Bldder Cncer Met-nlysis Collbortion: Neodjuvnt chemotherpy in invsive bldder cncer: systemtic review nd met-nlysis. Lncet 23; 361: Turker P, Bostrom PJ, Wroclwski ML, vn Rhijn B, Kortekngs H, Kuk C, Mirtti T, Fleshner NE, Jewett MA, Finelli A, Kwst TV, Evns A, Sweet J, Lto M, Zlott AR: Upstging of urothelil cncer t the time of rdicl cystectomy: fctors ssocited with upstging nd its effect on outcome. BJU Int 212; : 4. Murer et l /1/214 7:2:52 AM

7 6 Shrit SF, Plpttu GS, Krkiewicz PI, Rogers CG, Vzin A, Bstin PJ, Schoenberg MP, Lerner SP, Sglowsky AI, Lotn Y: Discrepncy between clinicl nd pthologic stge: impct on prognosis fter rdicl cystectomy. Eur Urol 27; 51: ; discussion Chpmn DM, Pohr KS, Gong MC, Bhnson RR: Preopertive hydronephrosis s n indictor of survivl fter rdicl cystectomy. Urol Oncol 29; 27: Stimson CJ, Cookson MS, Brocs DA, Clrk PE, Humphrey JE, Ptel SG, Smith JA Jr, Chng SS: Preopertive hydronephrosis predicts extrvesicl nd node positive disese in ptients undergoing cystectomy for bldder cncer. J Urol 21; 13: Lin HY, Wng SZ, Chen JX, Chen LW, Xio J: The prognostic vlue of hydronephrosis in bldder cncer treted by rdicl cystectomy. Urologi 2; 7: Green DA, Rink M, Hnsen J, Ch EK, Robinson B, Tin Z, Chun FK, Tgw S, Krkiewicz PI, Fisch M, Scherr DS, Shrit SF: Accurte preopertive prediction of non-orgnconfined bldder urothelil crcinom t cystectomy. BJU Int 213; 1: Mitr AP, Skinner EC, Mirnd G, Dneshmnd S: A precystectomy decision model to predict pthologicl upstging nd oncologicl outcomes in clinicl stge T2 bldder cncer. BJU Int 213; 1: Cnter D, Long C, Kutikov A, Plimck E, Sd I, Oblczynski M, Zhu F, Viterbo R, Chen DY, Uzzo RG, Greenberg RE, Boorjin SA: Clinicopthologicl outcomes fter rdicl cystectomy for clinicl T2 urothelil crcinom: further evidence to support the use of neodjuvnt chemotherpy. BJU Int 2; 17: Drieskens O, Oyen R, Vn Poppel H, Vnkn Y, Flmen P, Mortelmns L: FDG-PET for preopertive stging of bldder cncer. Eur J Nucl Med Mol Imging 25; 32: Gofrit ON, Mishni E, Orevi M, Klein M, Freedmn N, Pode D, Shpiro A, Ktz R, Libson E, Chisin R: Contribution of C-choline positron emission tomogrphy/computerized tomogrphy to preopertive stging of dvnced trnsitionl cell crcinom. J Urol 26; 176: ; discussion Anjos DA, Etchebehere EC, Rmos CD, Sntos AO, Albertotti C, Cmrgo EE: 1 F-FDG PET/CT delyed imges fter diuretic for restging invsive bldder cncer. J Nucl Med 27; 4: Jdvr H, Qun V, Henderson RW, Conti PS: [F-1]-Fluorodeoxyglucose PET nd PET-CT in dignostic imging evlution of loclly recurrent nd metsttic bldder trnsitionl cell crcinom. Int J Clin Oncol 2; 13: Kibel AS, Dehdshti F, Ktz MD, Klim AP, Grubb RL, Humphrey PA, Siegel C, Co D, Go F, Siegel BA: Prospective study of [1F] fluorodeoxyglucose positron emission tomogrphy/computed tomogrphy for stging of muscle-invsive bldder crcinom. J Clin Oncol 29; 27: Correltion of C-Choline PET/CT nd Survivl in Bldder Cncer 1 Swinnen G, Mes A, Pottel H, Vnneste A, Billiet I, Lesge K, Werbrouck P: FDG-PET/ CT for the preopertive lymph node stging of invsive bldder cncer. Eur Urol 21; 57: Apolo AB, Riches J, Schoder H, Akin O, Trout A, Milowsky MI, Bjorin DF: Clinicl vlue of fluorine-1 2-fluoro-2-deoxy-D-glucose positron emission tomogrphy/computed tomogrphy in bldder cncer. J Clin Oncol 21; 2: Lodde M, Lcombe L, Friede J, Morin F, Sourine A, Frdet Y: Evlution of fluorodeoxyglucose positron-emission tomogrphy with computed tomogrphy for stging of urothelil crcinom. BJU Int 21; 16: Goln S, Sopov V, Bniel J, Groshr D: Comprison of C-choline with 1 F-FDG in positron emission tomogrphy/computerized tomogrphy for stging urothelil crcinom: prospective study. J Urol 2; 16: Jensen TK, Holt P, Gerke O, Riehmnn M, Svolgrd B, Mrcussen N, Bouchelouche K: Preopertive lymph-node stging of invsive urothelil bldder cncer with 1 F-fluorodeoxyglucose positron emission tomogrphy/ computed xil tomogrphy nd mgnetic resonnce imging: correltion with histopthology. Scnd J Urol Nephrol 2; 45: Murer T, Souvtzoglou M, Kubler H, Opercn K, Schmidt S, Herrmnn K, Stollfuss J, Weirich G, Hller B, Gschwend JE, Schwiger M, Kruse BJ, Treiber U: Dignostic efficcy of [C]choline positron emission tomogrphy/computed tomogrphy compred with conventionl computed tomogrphy in lymph node stging of ptients with bldder cncer prior to rdicl cystectomy. Eur Urol 212; 61: Orevi M, Klein M, Mishni E, Chisin R, Freedmn N, Gofrit ON: C-cette PET/CT in bldder urothelil crcinom: intrindividul comprison with C-choline. Clin Nucl Med 212; 37:e67 e Schoder H, Ong SC, Reuter VE, Ci S, Burnzi E, Dlbgni G, Lrson SM, Bochner BH: Initil results with ()C-cette positron emission tomogrphy/computed tomogrphy (PET/CT) in the stging of urinry bldder cncer. Mol Imging Biol 212; 14: Vrgs HA, Akin O, Schoder H, Olgc S, Dlbgni G, Hrick H, Bochner BH: Prospective evlution of MRI, C-cette PET/CT nd contrst-enhnced CT for stging of bldder cncer. Eur J Rdiol 212; 1: Liedberg F, Mnsson W: Lymph node metstsis in bldder cncer. Eur Urol 26; 49: Shrit SF, Ehdie B, Rink M, Ch EK, Svtek RS, Chromecki TF, Fjkovic H, Novr G, Dvid SG, Dneshmnd S, Frdet Y, Lotn Y, Sglowsky AI, Clozel T, Bstin PJ, Kssouf W, Fritsche HM, Burger M, Izw JI, Tilki D, Abdollh F, Chun FK, Sonpvde G, Krkiewicz PI, Scherr DS, Gonen M: Clinicl nodl stging scores for bldder cncer: proposl for preopertive risk ssessment. Eur Urol 212; 61: DOI: 1.59/ Sobin LH, Fleming ID: TNM Clssifiction of Mlignnt Tumors, fifth edition (1997). Union Interntionle Contre le Cncer nd the Americn Joint Committee on Cncer. Cncer 1997; : Schemper M, Smith TL: A note on quntifying follow-up in studies of filure time. Control Clin Trils 1996; 17: Gry B: Pckge cmprsk uem.mx/r-mirror/web/pckges/cmprsk/ cmprsk.pdf. 32 Liedberg F, Bendhl PO, Dvidsson T, Gudjonsson S, Holmer M, Mnsson W, Wllengren NO: Preopertive stging of loclly dvnced bldder cncer before rdicl cystectomy using 3 tesl mgnetic resonnce imging with stndrdized protocol. Scnd J Urol 213; 47: Nkgw T, Kni Y, Nknishi H, Komiym M, Fujimoto H: Chrcteristics of lymph node metstses defining the outcome fter rdicl cystectomy of urothelil bldder crcinom. Jpn J Clin Oncol 212; 42: Simone G, Ppli R, Ferriero M, Guglinone S, Nselli A, Collur D, Introini C, Puppo P, Muto G, Gllucci M: Development nd externl vlidtion of lymph node density cut-off points in prospective series of rdicl cystectomy nd pelvic lymph node dissection. Int J Urol 212; 19: Lee EK, Herr HW, Dickstein RJ, Kssouf W, Munsell MF, Grossmn HB, Dinney CP, Kmt AM: Lymph node density for ptient counselling bout prognosis nd for designing clinicl trils of djuvnt therpies fter rdicl cystectomy. BJU Int 212; :E59 E Bruins HM, Hung GJ, Ci J, Skinner DG, Stein JP, Penson DF: Clinicl outcomes nd recurrence predictors of lymph node positive urothelil cncer fter cystectomy. J Urol 29; 12: Picchio M, Treiber U, Beer AJ, Metz S, Bossner P, vn Rndenborgh H, Pul R, Weirich G, Souvtzoglou M, Hrtung R, Schwiger M, Piert M: Vlue of C-choline PET nd contrst-enhnced CT for stging of bldder cncer: correltion with histopthologic findings. J Nucl Med 26; 47: Drzezg A, Souvtzoglou M, Eiber M, Beer AJ, Furst S, Mrtinez-Moller A, Nekoll SG, Ziegler S, Gnter C, Rummeny EJ, Schwiger M: First clinicl experience with integrted whole-body PET/MR: Comprison to PET/ CT in ptients with oncologic dignoses. J Nucl Med 212; 53: /1/214 7:2:52 AM