pelvic radiation may be associated with an elevated risk of secondary bladder malignancies that may be seen as early as five years after exposure .  
intravesical bcg therapy is a standard treatment for high - risk nonmuscle - invasive bladder cancer ( nmibc ) ( clinical stages ta , tis , and t1 ) .
we have previously shown that 50% of patients with nmibc who were previously exposed to prostate rt will have a durable response to intravesical bcg .
we now report our experience with radical cystectomy after failed bcg immunotherapy for high - risk nmibc in men with and without a prior history of rt for pc .
with institutional review board approval , we retrospectively identified all patients who underwent radical cystectomy for recurrent / persistent high - risk nmibc urothelial carcinoma and received intravesical bcg therapy from a dataset of nearly 1500 cystectomy patients at two academic medical centers from 1995 to 2008 .
we divided this cohort into three groups based on the history of pc and its associated treatment modality : ( 1 ) those with a history of pc treated with rt , ( 2 ) those who underwent prior radical prostatectomy ( rp ) alone , and ( 3 ) those without pc treatment prior to radical cystectomy .
the three groups were compared focusing on perioperative complications , histopathologic findings , and clinical outcomes .
all patients who received brachytherapy and/or external beam radiotherapy as primary treatment or as adjuvant treatment following rp or as salvage for locally - recurrent pc were included in group 1 .
statistical analyses were performed by means of fisher 's exact , chi square , t - test , anova , and kaplan - meier methods using spss version 16 ( spss , chicago , il , usa ) .
all statistical analyses were 2 sided , and p < 0.05 was considered statistically significant .
we identified 53 patients who underwent radical cystectomy for nmibc after failed bcg therapy from two academic medical centers .
twelve had previous prostate rt ( group 1 ) , 6 had a history of pc treated with rp alone ( group 2 ) , and 35 had no history of pc or rt exposure ( group 3 ) .
patient age was significantly different between groups , with the irradiated group being older than the other groups ( p = 0.01 ) .
clinical stages were not significantly different between groups . the differences in transfusion rate and estimated blood loss were not statistically significant .  
pathological upstaging ( pt24 or pn13 ) was 58% in group 1 , 29% in group 2 , and 20% in group 3 ( p = 0.01 ) .
extravesical extension ( pt3 ) was also significantly higher in group 1 versus group 3 patients ( p < 0.02 ) .
the incidence of carcinoma in situ in pathological specimens was highest in group 3 ( p < 0.001 ) .
the number of positive margins was not statistically different between the three groups ; however , local recurrences ( defined as pelvic soft tissue or urethra ) were highest in group 1 ( 42% ) .
residual prostate cancer was identified in two patients in group 1 and one patient in group 2 .
one patient from group 1 required androgen deprivation therapy due to recurrent prostate cancer after cystectomy .  
intraoperative complications included a rectal injury in group 1 and an obturator nerve injury in group 3 .
the rate of ureteroenteric obstruction requiring nephrostomy tube placement was also higher in group 1 with a total of 6 kidneys out of 24 requiring temporary drainage ( p = 0.001 ) . in group 1
nephrostomy tubes were placed in three patients for anastomotic strictures and one patient due to upper tract urothelial malignancy . in group 3 ,
nephrostomy tube drainage was required for two patients , one with an anastomotic stricture and the other with an upper tract recurrence causing obstruction . of the patients that were initially managed with nephrostomy tube drainage , only one patient in group 3 required antegrade incision and dilation of an anastomotic stricture . in the remaining patients
, the nephrostomies were removed without further sequelae , and no further intervention was required at the last follow - up .
the majority of complications occurring in group 2 were related to urinary continence issues with patients requiring urethrotomy or artificial urinary sphincter placement .
postoperative clavien major and minor complications were not significantly different , and there were no perioperative mortalities within 30 days of surgery .
recurrence - free survival was significantly worse for the patients with previous prostate rt ( 42% ) compared to the group with previous prostatectomy ( 100% ) and those with no history of prostate cancer or rt ( 71% ) ( p < 0.01 ; figure 1 ) .
  we previously reported that the efficacy of bcg may be diminished after pc rt with only 50% showing a durable response to intravesical therapy .
as such , we sought to assess the outcomes of the patients with high - risk nmibc refractory to intravesical bcg that underwent radical cystectomy . to our knowledge , this is the first study to specifically analyze the outcomes of cystectomy for bcg - refractory nmibc in patients with prior prostate rt . in the present series ,
those patients with a history of prior prostate rt were significantly more likely to be clinically understaged and more importantly demonstrated a higher risk for disease recurrence following radical cystectomy than those without previous exposure to pelvic radiation .  
other studies have similarly shown that patients who undergo radical cystectomy after rt for pc have a high rate of nonorgan - confined disease , between 5060% [ 3 , 6 ] .
the prevalence of pathological upstaging seen in the cystectomy cohort with prior rt is concerning . in the present study , despite the shorter follow - up period , the majority of patients with prior rt who underwent cystectomy for failed bcg therapy recurred primarily within the pelvis . whether  earlier  consideration of radical cystectomy in the setting of nonmuscle - invasive bladder cancer and previous prostate radiotherapy would improve these outcomes remains to be determined .
in addition , improvement in initial radiologic staging as well as subsequent imaging at the time of disease recurrence is of paramount importance .
it is likely that the burden of disease in the patients who underwent cystectomy was significantly underestimated at the time of the initial diagnosis of urothelial carcinoma of the bladder .  
patients who undergo radical cystectomy after previous pc / rt have a higher rate of complications .
eisenberg et al . reported a 21.1% rate of major urinary diversion - related complications in a cohort of salvage cystectomy patients .
ramani et al . demonstrated a higher stricture rate in patients treated with primary radiotherapy for pelvic malignancy and then undergone salvage cystectomy .
our higher rate of postoperative nephrostomy drainage in the rt group indicates that rt may be a risk factor for ureteroenteric anastomotic obstruction , likely a result of ischemia secondary to effects on the microcirculation of the distal ureter and/or bowel .
resection of the ureter more proximally ( above the common iliac bifurcation ) in patients with previous pelvic radiotherapy may help prevent ureteroenteric strictures .
it is a small retrospective study of patients treated at 2 academic medical centers over a 13-year period .
both centers have tertiary referral practices , and thus the patients treated may be at higher risk than would be seen in the community setting .
therefore , we may be overestimating the problem of clinical understaging at the time of cystectomy in the post - rt patients .
furthermore , the utilization of newer modalities of radiotherapy , such as intensity modulated radiotherapy , has changed over the last decade which may impact our findings .
although our sample size is small , it adds to the other prior small published series evaluating radical cystectomy outcomes of patients with prior prostate rt [ 11 , 12 ] .
intravesical bcg therapy may not be as effective for nonmuscle - invasive bladder cancer in the setting of prior prostate radiotherapy as evidenced by the high rate of pathologic upstaging .
radiation - induced bladder cancer may represent a more aggressive phenotype for which early consideration for radical cystectomy should be given .
 
 purpose . 
 intravesical bacillus calmette - guerin ( bcg ) immunotherapy is indicated for high - grade nonmuscle - invasive bladder cancer ( nmibc ) . 
 the efficacy of bcg in patients with a history of previous pelvic radiotherapy ( rt ) may be diminished . 
 we evaluated the outcomes of radical cystectomy for bcg - treated recurrent bladder cancer in patients with a history of rt for prostate cancer ( pc ) . 
 methods . 
 a retrospective chart review was performed to identify patients with primary nmibc . 
 we compared the outcomes of three groups of patients who underwent radical cystectomy for bcg - refractory nmibc : those with a history of rt for pc , those who previously underwent radical prostatectomy ( rp ) , and a cohort without pc or rt exposure . 
 results . from 1996 to 2008 , 53 patients underwent radical cystectomy for recurrent nmibc despite bcg . those with previous pelvic rt 
 were more likely to have a higher pathologic stage and decreased recurrence - free survival compared to the groups without prior rt exposure . 
 conclusion . 
 response rates for intravesical bcg therapy may be impaired in those with prior prostate radiotherapy . 
 patients with a history of rt who undergo radical cystectomy after failed bcg are more likely to be pathologically upstaged and have decreased recurrence - free survival . earlier consideration of radical cystectomy may be warranted for those with nmibc who previously received rt for pc . 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusions