Bladder Cancer Post AUA 2008

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Bladder Cancer: Post AUA-2008 Wes Kassouf, MD MUHC-Montreal General Hospital June 7, 2008

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#935 Prostate radiotherapy: what is the contemporary risk of bladder carcinoma? SEER database 243,082 pts treated for PCa from 1988-2003 RP (45%), EB (38%), BT (9%), EB-BT (7%) In multivariate analysis, radiation for PCa associated with increased risk of bladder cancer compared to pts undergoing RP (RR 1.52-1.85) and compared to general population Pts should be counseled appropriately regarding these long-term complications

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Utility of Urine Cytology #940 Urine cytology is of no added value in the primary evaluation of pts with hematuria (n=1841) #941 Urine cytology in the evaluation of urological malignancy revisited-is it still necessary? (n=2568) #942 Utility of urine cytology in the workup of aymptomatic microscopic hematuria (n=190) Routine urine cytology may not be cost effective in the initial evaluation of hematuria

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#943 What is the natural history of frank hematuria after initial investigations? Prospective study 1999-2001 378 pts had negative initial gross hematuria workup Mean f/u 6.9yrs 9.1% died of GU cancers 20% had repeated gross hematuria Of these, 50% received a significant urological diagnosis (stones and ca) Majority of pts cleared by initial w/u will remain asymptomatic Repeat workup of pts who develop recurrent gross hematuria is warranted

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#1694: Risk of persistent local disease in bladder cancer patients found to be pT0 at cysectomy 33% of patients who had preoperative chemotherapy for >T3 had LN mets No pt with

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#1557: Risk factors for UC of prostate in pts undergoing radical cystectomy for bladder cancer 39% of cystectomy patients had prostatic urethral involvement Only associated CIS and tumor size (>2cm) were significantly associated with UC in the prostate

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#1695: Gender and racial differences in bladder cancer mortality: How much a role does tumor factors play at presentation SEER database 60% of all deaths from bladder cancer are within 2 years of diagnosis Tumor characterstics and age account for half of the excess mortality seen in women and African Americans other confounders (smoking, choice of therapies) may also play important role

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#1699: Oncologic follow-up after radical cystectomy: is there any benefit? 49% of patients will recur after radical cysectomy with a median time to recurrence of 20 months 35% asymptomatic recurrences No difference in OS at 1, 2, and 5 years after first recurrence in asymptomatic and symptomatic patients No survival benefit to metastatic screening Need to follow upper tracts

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Abstract 198: Mulit-institutional evaluation of p53 immunohistochemical staining in patients with organ-confined at radical cystectomy 272 pts, 5 centers pT1-2N0M0 TCC at surgery P53 altered status (automated measurement; cut-off at 10% nuclear reactivity) Increased recurrence (HR 4.9) Increased cancer-specific mortality (HR4.9) p53 status increased predicitve accuracy even after adjusting for grade, stage, LVI, # of nodes p53 evaluation may help identify patients who may benefit from adjuvant chemotherapy after cystectomy

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#697: Trends in urinary diversion following radical cystectomy in the US 51,619 cystectomies 1997-2005 Continent diversion 4.8% - 10.9% Younger pts, males, and those with private insurance are more likely to undergo continent urinary diversions Reconstruction rose significantly at high volume hospitals but not low volume hospitals Efforts must be made to optimize quality care in radical cystectomy population

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#710: Radical cystectomy and ileal neobladder: impact of BMI on early postoperative care Obesity is associated with higher rate of local complications and incision hernias With modern perioperative care, the rate of life threatening complications was same as pts with normal BMI

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#699: Long-term oncologic outcomes in women undergoing radical cystectomy and orthotopic diversion for bladder cancer (USC) #700: Long term outcome of radical cystectomy and orthotopic neobladder diversion in women (UCSF) #701: Functional and oncologic outcomes after orthotopic urinary diversion in women (Mayo clinic) Oncologic outcomes after orthotopic diversion in women

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Oncologic outcomes after orthotopic diversion in women USC UCSF Mayo # of pts 120 38 60 Urethral recurr 1 3 1 Local rec 2 0 2 Tumor stage 61% 68% 58% (organ confined) Conclusions: good results in well selected females (Most other series 2/3 of pts are non-organ confined)

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#700: Long term outcome of radical cystectomy and orthotopic neobladder diversion in women (UCSF) #701: Functional and oncologic outcomes after orthotopic urinary diversion in women (Mayo clinic) #702: Nocturnal incontinence is a significant problem after orthotopic bladder substitution in women (Mansoura) Functional outcomes after neobladder in women

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Functional outcomes after orthotopic urinary diversion in women UCSF Mayo Mansoura # of pts 38 60 201 Retention 24% 28% 19% Incontinence Daytime 17% Nocturnal 39% 35% 28% Pts should be aware that they may need to convert to continent cutaneous reservoir

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#696: Orthotopic neobladders: meta-analysis of outcomes 20 series with a total of 3994 patients Incontinent rates Night time 13% Day time 4.8% Too optimisitc results!

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#705: Excellent long-term spontaneous voiding for neobladder if appropriate surgery is implemented for frequent secondary outflow obstruction in males University of Bern urinary retention (20-25%) 12% within the first 5 years after surgery 13% between postop years 5 to 10 Most due to stricture, protrusions of bowel mucosa, prostatic regrowth 96% of pts were able to void spontaneously at 10yrs after treatment of outlet obstruction CIC can be avoided in most pts

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Pure laparoscopic radical cystectomy #1555 Comparison between open and laparoscopic assisted radical cystectomy for bladder cancer (Cleveland Clinic) #991: Laparoscopic radical cystectomy: the experience in a university hospital (Spain) #1609: Single center experience in laparoscopic radical cystectomy (France)

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Cleveland LRC (n=50), ORC (n=50) OR times longer in LRC (6.3 hr vs 5.3hrs) EBL lower in LRC (363cc vs 804cc) Transfusion lower in LRC (12% vs 40%) Time to oral intake lower in LRC (3.4 days vs 4.2 days)

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RAL vs open radical cystectomy (Chapel Hill) Extracorporeal diversion Ileal conduit – robotic (58%), open (83%) Ileal neobladder – robotic (42%), open (17%) OR time EBL # LN Time to DC Robotic 5.4hr 294cc 19 4.4 days (n=33) Open 3.7hr 588cc 16 5.3 days (n=42)

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#850 International robotic-assisted cystectomy (RARC) consortium: immediate oncologic results after 162 cases 2002-2007, 162 RARC at 4 academic institutions pT2 or less 56%. pT3 or more 44% Median # of nodes 18 Positive surgical margins 8% Oncologic safety of lap RC or RAL RC is uncertain?

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#709: Urinary diversion-related complications: Lap vs open radical cystectomy (Cleveland Clinic) Lap Open # of pts 41 53 Ileal conduit 78% 85% No difference in intraoperative and early postop complications except Ureteral stenosis is higher in lap (7% vs 3%)

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#711: Is endoscopic balloon dilation of ureteral strictures alternative to open surgery? (Germany) 40 ureteral stenoses Less than 1cm length Median of 4 dilatations in monthly intervals Follow-up 16.6 months Success rate Short term 60% Long term 45%

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#1558: Ureteral frozen sections at time of radical cystectomy: reliability and clinical implications (UWO) 391 cystectomies Abnormality at frozen section in 9.9% and 2.9% of final ureteral margins No difference in recurrence between –ve and +ve margins *dysplasia, atypia, and CIS was considered +ve Bladder CIS was independent predictor of abnormality in ureteral frozen section Frozen ureteral margins may overestimate the positive final ureteral margins

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#1793: Natural history of CIS after complete initial response to BCG 104 pts CR to BCG at 3 months Some had maintenance RFS, PFS, and CSS 5-yrs: 64%, 79%, and 90% 10-yrs:54%, 77%, and 86%

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Abstract #1791: Prognostic value of re-TUR of high risk noninvasive bladder cancer T1G3 Pathology on re-TUR recurrence progression DFS T0 17% 10% 78% Ta/1 45% 23% 50%

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#1790: Protein expression patterns of Ezrin are predictors of progression in T1G3 bladder tumors treated with BCG 92 pts with T1G3 who failed BCG Ezrin (membrane protein) was measured in tumors Less than 20% Ezrin expression associated with progression and OS May be an indicator of aggressive T1 tumors

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#337 Intravesical docetaxel for high risk NMIBC who failed intravesical tx Phase I trial 18pts received intravesical docetaxel x 6wks 39% NED at 2 years

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#1796: Phase I study of multi-dose administration of intravesical CG0070 in pts with NMIBC CG0070 Oncolytic adenovrial vector Activates GM-CSF in primarily RB defective cells Direct and surround kill Low toxicity and effective in Phase I trial Immune response blunted GM-GSF production in urine many-fold on subsequent instillations Problem with future agents that require multiple instillations

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Predictors of intravesical chemotherapy use in superficial bladder cancer: results from the SEER 2003 patterns of care project 42% received intravesical chemotherapy Factors associated with intravesical chemo use were Stage and grade Race and ethnicity Geographic region

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# 843 Outcome of bladder cancer patients managed with partial cystectomy in Quebec: Impact of treatment delay 714 pts, median f/u 4.6 years 52 (7.3%) required salvage radical cystectomy Treatment delay (>12 weeks) associated with higher rate of salvage cystectomy Pts treated with salvage partial cystectomy post partial Cx had significantly shorter survival compared to those treated with upfront radical cystectomy

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#842 Oncological evaluation of the prostate-sparing cystectomy: long-term results 117 pts, mean f/u 55 months Locoregional recurrence 4.7% Metastatic disease 34% 5-yr OS pT3N0 45% pN+ 22%

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Adjuvant chemotherapy for upper tract TCC #333 Adjuvant chemotherapy for upper tract TCC: results from the upper tract TCC consortium (n=516) #334 Adjuvant Gem-Cis chemotherapy of invasive TCC of the upper tract (n=51) The benefit of adjuvant chemotherapy for upper tract TCC is unclear

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Upper Tract TCC Consortium #832 Outcomes of radical nephroureterectomy for urothelial carcinoma: a contemporary series from the upper tract urothelial carcinoma collaboration #833 Impact of tumor location on prognosis for upper-tract urothelial carcinoma: outcomes from over 1300 patients #834 More extensive lymphadenectomy improves the prognosis of patients with upper tract urothelial carcinoma without nodal metastases

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Largest mulitcenter series for upper tract TCC 1363 pts treated with nephro-u All path re-reviewed by local GU pathologist After mean f/u of 51 months, 28% recurred outside bladder and 23% DOD Stage: < pT1 (43%), pT2 (19%), pT3 (33%), pT4 (5%) 5-yr RFS and CSS was 69% and 73% Upper Tract TCC Consortium

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On multivariate analysis, variables associated with CSS and RFS Tumor grade Stage Sessile tumor architecture LVI # of nodes removed was associated with CSS only in pN0 patients Tumor locations was not prognostic

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935 Prostate radiotherapy: what is the contemporary risk of bladder carcinoma? SEER database . 243, more 935 Prostate radiotherapy: what is the contemporary risk of bladder carcinoma? SEER database . 243,082 pts treated for PCa from 1988-2003 less
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