Best of the 2007 AUA Annual Meeting (2)

Meeting Review

RIU0370_12-12.qxd 12/12/07 8:30 PM Page 220 MEETING REVIEW Best of the 2007 AUA Annual Meeting (2) Bladder Cancer Highlights from the 2007 Annual Meeting of the American Urological Association, May 19-24, 2007, Anaheim, CA [Rev Urol. 2007;9(4):220-234] © 2007 MedReviews, LLC Key words: Age • Bladder cancer • Cystectomy • Cystoscopy • Gender • Intravesical therapy • Invasive cancer • Laparoscopic surgery • Lymph node dissection • Lymphovascular invasion • Metastatic cancer • Outcomes • Prognosis • Quality of life • Repeat TUR • Risk factors • Robotic-assisted surgery • Superficial cancer ore than 1700 abstracts were presented at the annual scientific meeting of the American Urological Association, including the full spectrum of superficial, invasive and metastatic bladder cancer. Reviews in Urology continues its coverage with contributing editor John Stein’s report on the work that he considered most clinically relevant to the treatment of bladder cancer. (For additional reports, see: Brawer MK, Makarov DV, Partin AW, et al. Best of the 2007 AUA Annual Meeting: Highlights from the 2007 Annual Meeting of the American Urological Association, May 19-24, 2007, Anaheim, CA. Rev Urol. 2007;9:133-154.) M Cystectomy Bartsch and associates1 analyzed the incidence of clinically relevant Reviewed by John P. Stein, MD, Keck School of Medicine, University of Southern California, Los Angeles, CA. 220 VOL. 9 NO. 4 2007 prostate cancer in patients undergoing radical cystectomy for bladder cancer. A total of 1076 male patients underwent radical cystectomy, and 267 patients (25%) were found to have pathologic evidence of prostate cancer. The median serum-PSA was 2.3 ng/mL for those with prostate cancer compared with 1.3 ng/mL for those without prostate cancer. As expected, the detection rate of prostate cancer significantly increased from 7.7% to 33.4% when the histopathologic evaluation of the prostate was optimized to a whole mount technique. The incidence of Gleason
6 and locally advanced tumors decreased to about 10% each in the more contemporary series (after 1994). The overall rate of postoperative PSA-progression in this series was 1%. The authors note that the cure rate for prostate cancer by radical cystectomy was extremely high. Furthermore, it should be noted that a significant number of patients with REVIEWS IN UROLOGY bladder cancer have prostate cancer, which increases significantly with age, and these implications should be considered when prostate-sparing techniques are contemplated in patients with bladder cancer requiring cystectomy. There is an unsubstantiated notion that prostate-sparing techniques will decrease the potential morbidity of radical cystectomy, but there is also evidence that prostate-sparing techniques may compromise the oncologic outcomes of the surgical procedure. In order to identify risk factors for predicting occult prostate malignancy prior to radical cystectomy for bladder cancer and to better select men who may benefit from prostate-sparing procedures, Kefer and associates2 retrospectively analyzed 171 consecutive males from 1995 to 2006. All patients underwent transurethral resection (TUR) of the bladder tumor and radical cystectomy. The prostate was evaluated RIU0370_12-12.qxd 12/12/07 8:30 PM Page 221 Best of the 2007 AUA Annual Meeting for cancer and involvement of the prostate with transitional cell carcinomas (TCC) in the cystectomy specimen. The prostates were step sectioned at 3 mm intervals. Overall, 55 patients (32%) had TCC involvement of the prostate. Significant risk factors included tumor multifocality and bladder neck involvement with tumor. The authors also found 62 patients (36%) had occult prostate cancer. Risk factors for this included those with a PSA greater than 2.5, a positive digital rectal exam, and age greater than 60 years. Overall, only 7 of 170 patients (5%) had no risk factors for any prostate malignancy. The authors noted that the risk factors for predicting prostate involvement with any tumor (prostate or bladder) will identify only a small subset of patients who may subsequently consider a prostatesparing technique. On the other hand, it appears these data support the routine removal of the prostate during radical cystectomy from an oncologic perspective (Table 1). The treatment of patients with TCC involving the lamina propria (T1) remains a difficult and challenging clinical problem. Gupta and associates3 retrospectively evaluated the outcome of patients with clinical G3T1 bladder tumors treated with radical cystectomy at 3 US academic centers. A total of 171 patients (median age 67 years) were evaluated and categorized into pathologically down-staged, same-stage, or up-staged. Importantly, 17% of patients with T1 disease were found to have nodal metastases at the time of cystectomy. Pathologic upstage was seen in 51%, and extravesical tumor extension was seen in 27%. A delay of more than The presence of carcinoma in situ may be an important predictor of clinical outcomes in this high-risk group and may assist in directing treatment regarding earlier cystectomy. 3 months from the last TUR to cystectomy resulted in higher up-staging (71% vs 52%). As expected, these patients with pathologically upstaged tumors were more likely to die from cancer. Pre-cystectomy carcinoma in situ (CIS) was associated with higher recurrence rates and worse survival and was the only independent predictor of disease recurrence and survival in this cohort. The authors appropriately noted that, overall, a large portion of patients with T1 disease are upstage at cystectomy and have Table 1 Risk Factors Predicting PI-TCC Preoperative Risk Factors suboptimal outcomes. The presence of CIS may be an important predictor of clinical outcomes in this high-risk group and may assist in directing treatment regarding earlier cystectomy. Bader and associates4 evaluated their institutional experience with early cystectomy for G3T1 bladder tumors. Of 735 patients undergoing surgery for bladder cancer between 1989 and 2003, 134 (18%) were considered to have clinical G3T1 disease Total (N  171) PI-TCC PI-TCC CIS Present 48 20 (42%) 28 (58%) CIS Absent 123 35 (28%) 88 (72%) MF Present 73 31 (42%) 42 (58%) MF Absent 98 24 (24%) 74 (76%) BNTI Present 95 44 (46%) 51 (54%) BNTI Absent 76 11 (15%) 65 (85%) Repeat TUR OR (P Value) 1.8 (.09) 2.28 ( .02) 5.10 ( .0001) PI-TCC, prostatic involvement of transitional cell carcinoma; CIS, carcinoma in situ; MF, multifocal tumors; BNTI, bladder neck/trigone involvement; OR, object relation. Reproduced from Kefer et al2 with permission of the American Urological Association. and underwent cystectomy. Overall, 17% of patients were upstaged and one-third of these had nodal involvement. The overall and cancer-specific survival at 5 years for the entire cohort was 78% and 88%, respectively. These outcomes appear more favorable compared with more conservative measures for G3T1 disease where at least one-third of patients will die from the disease. The authors commented that compared with bladder preservation therapy, an early cystectomy allows for excellent outcomes for G3T1 disease. Nevertheless, one must carefully counsel these patients on the potential treatment options and associated risks of therapy as well as the long-term outcomes. There has been a growing body of evidence to support the concept of a repeat TUR for high-risk bladder cancer patients. There is a belief that a repeat TUR that includes muscle in the specimen provides better clinical staging and has therapeutic value as well. To evaluate this concept, Park and associates5 investigated the natural history of primary G3T1 bladder cancer without repeat TUR to determine if VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 221 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 222 Best of the 2007 AUA Annual Meeting continued the presence or absence of muscularis propria in the TUR specimen influences clinical outcomes. Data from 146 patients with G3T1 bladder cancer following TUR were retrospectively reviewed. The mean follow-up in this cohort was 52 months. Overall, 83% of patients were treated with intravesical therapy. Of the 146 patients, 94 had muscle in the TUR specimen (group 1) and 52 did not (group 2). There were no differences in the clinical and pathologic characteristics of these groups. Overall, there was no significant difference in recurrence observed between groups 1 and 2 (38% vs 46%, respectively). Progression was also similar between the Urologic Association and is thought to provide diagnostic and potentially therapeutic benefits. From 2003 through 2005, 168 TURs were performed with an additional tumor bed biopsy for superficial bladder cancer including: 19% with T1 tumors, 20% with high-grade disease, 8% with associated CIS, 4% with multifocal tumors, and 33% for recurrent disease. The median follow-up was 1 year. A tumor bed biopsy site demonstrated tumor in 33% of patients, which was associated with high-grade (G3) tumors. In multivariate analysis, only recurrence status, tumor multifocality, morphology, and a positive tumor bed biopsy demonstrated a significant risk Although this report is slightly contrary to others in the literature . . . it does suggest that we may not need to reTUR all patients with this disease but rather may better select patients who require this procedure. groups (10% vs 11%). Furthermore, no differences were observed in 5-year recurrence-free survival, progressionfree survival, and cancer-specific survival. Only non-papillary tumor shape was found to influence progression, which occurred in 6% of those with papillary and 16% of those with non-papillary tumor. The authors recommended that repeat TUR should only be performed in those patients with G3T1 tumors that were non-papillary. Although this report is slightly contrary to others in the literature that advocate routine repeat TUR with the inclusion of muscle in the specimen for high-risk patients with superficial bladder cancer, it does suggest that we may not need to reTUR all patients with this disease but rather may better select patients who require this procedure. Forster and associates6 evaluated the utility of an additional resection biopsy of the tumor bed after the TUR has been completed. This has been part of the guideline of the German 222 VOL. 9 NO. 4 2007 for tumor recurrence. These findings suggest that those patients with positive tumor bed biopsy sites may benefit from a repeat TUR. Intravesical Therapy In an interesting report on superficial bladder cancer, Hoffmann and associ- to have a significant induction of antiinflammatory Th2-type cytokines, which have been found ultimately to cause an attenuation of Th1-type immune response. To study this interaction and the hypothesis that statin use may attenuate the BCG response, the authors retrospectively evaluated the clinical outcomes of 84 patients who had received BCG therapy for non–muscle-invasive bladder cancer. Patients receiving statins were compared with those who were not. With a median follow-up of approximately 4 years, the number of recurrences did not differ between the groups, but 53% of the statin users developed more aggressive tumors compared with only 18% for the non-users. Furthermore, the number of patients requiring cystectomy was higher in the statin group (42%) compared with the non-statin group (14%). Although this association of statins and intravesical BCG therapy for patients with superficial bladder cancer must be further explored, this study found that statin users have increased risk of tumor progression and need for cystectomy. Thalmann and associates8 prospectively compared the recurrence and progression rates as well as the side Although this association of statins and intravesical BCG therapy for patients with superficial bladder cancer must be further explored, this study found that statin users have increased risk of tumor progression and need for cystectomy. ates7 evaluated the effects of statins in patients receiving intravesical treatment with Bacille-Calmette Guérin (BCG) therapy for bladder cancer. The successful administration of BCG and the improved clinical profile for highrisk, non–muscle-invasive TCC of the bladder are thought to correlate to high Th-1 type urinary cytokine levels. Statins are among the most commonly prescribed drugs in the United States to lower cholesterol and have been found REVIEWS IN UROLOGY effects in patients with high-risk, non–muscle-invasive TCC of the bladder who were treated with 2 different strains of intravesical BCG therapy. From 1998 to 2005, a total of 80 patients were randomized to receive 6 postoperative instillations of either Immucyst® (Sanofi Pasteur Inc., Swiftwater, PA) or Oncotice® (Organon International, Oss, Netherlands). Groups were similarly balanced with regard to stage, grade, CIS, recurrence, RIU0370_12-12.qxd 12/12/07 8:30 PM Page 223 Best of the 2007 AUA Annual Meeting and multifocality. With a median follow-up of 2.6 years, side effects were comparable in each group, 60% for Immucyst and 70% for Oncotice. Recurrence rates, however, were significantly higher in the Oncotice (68%) group compared with the Immucyst (31%) patients. The results from this randomized prospective trial are interesting and should be evaluated in a larger population group of patients with high-risk, superficial bladder cancer. These data also suggest that we still need to better define the treatment schedules, duration, and dosing of therapies and various strains of intravesical therapy. In another prospective randomized trial of intravesical BCG therapy for superficial bladder cancer, AliEl-Dein and associates9 evaluated and compared the efficacy and toxicity of multiple 3-week courses versus monthly instillations of maintenance therapy for T1 bladder cancer. A total of 84 patients with T1 TCC were randomized following an initial 6-week course of sequential BCG and epirubicin. Thirty-four patients (group 1) were randomized to a 3-week course at 3, 6, 12, 18, and 24 months, and 50 patients (group 2) were randomized to monthly BCG of the same dose for 1 year. With a mean follow-up of 51 months, both groups were comparable regarding clinical and tumor characteristics. Recurrence (26% group 1, 20% group 2) and progression (12% for each group) rates were comparable, but toxicity and side effects were significantly more frequent in group 1 (50% vs 20%). Maintenance BCG therapy is thought to improve the clinical outcomes in patients with high-risk, superficial bladder cancer, particularly with progression, but does carry the associated side effects. This study suggests similar efficacy with reduction in these side effects when maintenance is given monthly for a year. The standard therapy for CIS of the bladder is intravesical therapy with BCG, and data suggest that a second course of BCG may be effective for recurrent disease or those who fail initial therapy. To evaluate this concept, Hara and associates10 studied the effectiveness of a second course of intravesical BCG for CIS of the bladder for patients who fail to respond to initial therapy. A total of 185 patients with CIS of the bladder who underwent BCG therapy were evaluated. Of these, 160 (86%) had a complete response to the initial therapy with an overall progression-free survival of 75%. Of this group, 31 patients underwent a second course of BCG, including 9 immediately after the initial BCG treatment and 22 due to a recur- these outcomes may become even more ominous, and cystectomy may ultimately be the best long-term therapy. Nativ and associates11 evaluated the combination of mitomycin C and hyperthermia for patients with superficial bladder cancer following BCG failure. A total of 98 patients with Ta or T1 TCC (78% classified as highrisk) of the bladder who failed previous BCG therapy were subsequently treated with intravesical mitomycin hyperthermia. Treatment was weekly for 6 weeks, followed by maintenance at 6-week intervals for 6 sessions. Overall, 57% of these high-risk patients were disease free at 24 months. The average time to tumor recurrence was 15 months, and 2 patients (2%) demonstrated tumor progression. Risk These findings suggest that there is a group of patients with CIS who may benefit from a second course of BCG, but those who develop a recurrence after an initial response to BCG have a limited response to additional BCG with significant upper tract and prostate involvement. rence after an initial complete response. Of the 9 who did not initially respond, 8 (88%) had a complete response following a second BCG course, and 7 of these remained free of disease at 3 years. On the other hand, 17 of the 22 patients (77%) with recurrent disease had a complete response following a second course of BCG, but 7 of these 17 underwent cystectomy for disease progression. A total of 10 patients underwent cystectomy with significant involvement of the prostate (40%) and upper urinary tract (15%). These findings suggest that there is a group of patients with CIS who may benefit from a second course of BCG, but those who develop a recurrence after an initial response to BCG have a limited response to additional BCG with significant upper tract and prostate involvement. Furthermore, with longer follow-up, one would expect that factors for progression in this study included no maintenance therapy, high-risk category, and highly recurrent disease. The authors suggest that this therapy is a potential option for conservative therapy without undue risk of progression. It must be noted that the follow-up in these patients was short, and that if there is highrisk disease a more aggressive therapy such as cystectomy should at least be considered and discussed with the patient. This study also suggests the importance of maintenance therapy for treating superficial bladder cancer. In an interesting population-based, retrospective analysis of patients with superficial (stage I) bladder cancer, Spencer and associates12 evaluated the use of adjuvant therapy and the association with survival for patients with non–muscle-invasive bladder cancer. The SEER Medicare database VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 223 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 224 Best of the 2007 AUA Annual Meeting continued from 1991 to 2003 identified 21,593 patients over the age of 65 years with AJCC stage I bladder cancer. Patients were categorized as receiving adjuvant therapy (BCG or non-BCG such as mitomycin, thiotepa) or no therapy at all. Overall, 40% of patients received some adjuvant therapy. In multivariate analysis, disease-specific and overall survival were improved in those who received BCG adjuvant therapy, whereas only overall survival was improved with non-BCG adjuvant therapy. This study’s results must be interpreted with caution for various methodological reasons, but the data suggest there is a benefit of adjuvant intravesical therapy in men older than 65 years with superficial bladder cancer. Prognosis Dhar and associates13 evaluated and compared the local and distant recurrence rates for patients with muscleinvasive bladder cancer undergoing radical cystectomy for TCC of the bladder with a limited lymphadenectomy at the Cleveland Clinic in Ohio and a more extended lymphadenectomy group at the University of Bern in Switzerland. These were consecutive series of 385 patients from Cleveland (median age 62 years) and 394 Bern patients (median age 67 years). All patients were treated between 1987 and 2000, with a median follow-up of 45 months for Cleveland patients and 59 months for Bern patients. All patients were clinically node-negative stage preoperatively and none received any neoadjuvant radiation or systemic chemotherapy. The boundaries of the limited lymph node dissection (LND) were superiorly at the level of the common iliac bifurcation, whereas the extended LND was higher at the level where the ureters cross the common iliac vessels. Overall, the incidence of positive lymph nodes was higher in the extended LND group compared with the limited LND for each pathologic stage. Furthermore, incidences of local and distant recurrences were significantly higher in those undergoing limited LND at Cleveland Clinic. The authors appropriately recognized the inherent limitation of this retrospective institutional comparison, but these data clearly add to the growing body of evidence to support a more extended LND in patients with muscle-invasive bladder cancer requiring cystectomy (Table 2). The most well established risk factor for bladder cancer is cigarette smoking, which is seen in approximately 60% of patients with the disease. Hendricksen and associates14 studied the influence of smoking on the development of recurrences in Table 2 Number of Positive Nodes Associated With Recurrence Node
Patients Node
Patients With Recurrence 150 24/150 (16%) 14/24 (58%) 200 15/200 (7.5%) 13/15 (87%) pT3pNO-2 172 59/172 (34%) 38/59 (63%) pT3pNO-2 136 29/136 (21%) 27/29 (93%) Stage Total Patients Bern pT2pNO-2 Cleveland pT2pNO-2 Bern Cleveland Institution 13 Adapted from Dhar et al with permission from the American Urological Association. 224 VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY patients with non–muscle-invasive bladder cancer. A total of 731 patients who had undergone a TUR for intermediate or high-risk, non–muscleinvasive bladder cancer were randomized in a clinical trial evaluating the efficacy of 3 different schedules of epirubicin. Upon entry into the trial, patients were questioned regarding their smoking behavior and classified as smokers, ex-smokers, or nonsmokers. In addition, other factors were evaluated, including initiation, duration, and degree of smoking. In this cohort, 80% were males, with 88% of these men and 60% of the women having a history of smoking. When comparing the male and female recurrence rates and correcting for smoking behavior, it appears that smoking impacted recurrence-free survival. Of the smokers, ex-smokers, and non-smokers respectively, 39%, 44%, and 51% were recurrence-free at 5 years follow-up. Although this was not statistically significant, there was a clear trend in which smokers and ex-smokers develop more recurrences than non-smokers. More study will be required to understand the impact of current and previous smoking on bladder cancer recurrence, but it is becoming more apparent that cessation of smoking is an important component in improving outcomes for patients with this disease. Agud and associates15evaluated the prognostic value of the molecular staging technique of bladder cancer with KRT20 reverse transcriptase polymerase chain reaction (RT-PCR) in a group of 25 patients undergoing radical cystectomy for bladder cancer. KRT20 is a urothelium-specific molecule that is expressed in urothelium tumors and their metastases. This molecule was evaluated in peripheral blood, bone marrow, lymph nodes, normal mucosa, and primary bladder tumors and compared with negative control patients without a history of RIU0370_12-12.qxd 12/12/07 8:30 PM Page 225 Best of the 2007 AUA Annual Meeting bladder cancer. KRT20 was detected in all bladder tumors (100%) and in 23 of the 25 (92%) of normal bladder tissue samples in those with bladder cancer. No negative control demonstrated KRT20 expression. Lymph node metastases were documented routinely in 14 (56%) of patients, and all expressed KRT20 in the lymph nodes. In those without documented lymph node metastases, 27% were found to have micrometastases via KRT20 RT-PCR. Forty percent and 12% of patients demonstrated blood and bone marrow expression, respectively. Importantly, KRT20 lymph node expression showed a significant correlation with tumor progression, whereas blood and marrow demonstrated a strong correlation that did not reach statistical significance. The authors concluded that KRT20 RTPCR appears to be a reliable assay to detect pathologically positive lymph nodes and may also identify a group of patients who are at high risk for disease progression that would not be predicted on traditional histopathologic or microscopic techniques. Appropriately, the authors suggested evaluating this technique prospectively in a larger cohort to validate these interesting results. Rodriguez and associates16 analyzed the clinical outcomes and precystectomy prognostic factors in patients without evidence of disease (pT0) in the cystectomy specimen following radical cystectomy for TCC of the bladder. Of 1114 patients, 141 (12%) were pathologically pT0 with a disease-specific survival of 79%. In multivariate analysis, more than 5 relapses prior to cystectomy and the presence of vascular invasion in the TUR specimen were significant risk factors for survival. The authors appropriately noted that despite excellent clinical outcomes in the majority of patients with no evidence of tumor on the final pathologic specimen, not all patients with pT0 disease are cured. The oncologic outcomes of this pathologic stage are, in fact, similar to those patients with muscle-invasive disease (pT2) following cystectomy. Although the highest clinical stage at TUR was not a risk factor in this cohort, other known risk factors such as vascular invasion and, potentially, a delay in cystectomy (5 previous TURs) appear to impact outcomes in this group as well, suggesting that delays and certain histologic findings may influence outcomes with this disease. In a similar study from a different institution, Colombo and associates17 evaluated the clinical outcomes of patients with pT0 following cystectomy for TCC of the bladder. A total of 822 patients underwent radical cystec- The presence of lymphovascular invasion (LVI) is increasingly recognized as an independent risk factor identified in TUR bladder tumors as well as in the cystectomy specimen. Data suggest that those patients with LVI on a TUR specimen may be better treated aggressively, and those with LVI on the cystectomy specimen may be at risk for progression and benefit from adjuvant therapy following surgery. What is not known is the concordance status of LVI on the TUR and subsequent cystectomy specimen. Kunju and associates18 evaluated 76 TUR specimens and compared them with the pathology of the cystectomy specimens. Overall, LVI was detected on 22% of the TUR and 39% of the cystectomy specimens. There was a significant lack of concordance observed This study also confirms the notion that pT0 disease has similar outcomes compared with muscle-invasive bladder cancer and that a node dissection is an important component in this group of patients with a small incidence of nodal involvement. tomy for TCC with 102 (12%) demonstrating no residual tumor pathologically. Of this group, 70% had the TUR specimen available for clinical staging. Four patients (4%) had nodal involvement. At 5 years, the cancer-specific survival was 77%. Multivariate analysis revealed that number of lymph nodes removed and presence of lymph node involvement were the only significant predictors of bladder cancer outcome. The authors concluded that a significant percentage (23%) of pT0 patients die of bladder cancer with risk factors that include nodal involvement and number of nodes removed. This study also confirms the notion that pT0 disease has similar outcomes compared with muscleinvasive bladder cancer and that a node dissection is an important component in this group of patients with a small incidence of nodal involvement. between these 2. This difference was primarily related to false negative evaluation on the TUR specimen. These data suggest that the clinical finding of LVI at TUR may be helpful in treatment decisions, but the absence does not preclude the finding at the time of cystectomy. Long-term survival is seen in about one-third of lymph node positive patients, suggesting a therapeutic benefit of lymphadenectomy at surgery. The exact extent of the node dissection remains debatable. Wright and associates19 evaluated the association between the extent of the lymphadenectomy and survival in patients with lymph-node-positive disease following radical cystectomy. A total of 5201 patients from the SEER database (1988-2003) with TCC of the bladder who underwent radical cystectomy and lymphadenectomy were VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 225 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 226 Best of the 2007 AUA Annual Meeting continued evaluated. Patients with distant metastases were excluded from analysis. Outcomes were analyzed according to total nodes removed, total nodes involved and uninvolved, and lymph node density. Overall, 24% of patients had nodal involvement at surgery. The median number of nodes removed was 9 (range, 1 to 48) with a median number of nodes involved of 2 (range, 1 to 18). The median lymph node density was 22%. In multivariate analysis, the total number of positive nodes and the number of nodes removed remained significant risk factors for survival. Removal of more than 7 lymph nodes was associated with increased survival. The authors found that patients with a lymph node density of less than 12.5% demonstrated an improved survival compared with those with a lymph node density of 12.6% to 25%. The authors appropriately suggest that the number of uninvolved lymph nodes removed at the time of cystectomy is associated with an improved survival in node-positive patients. Although not evaluated in this study, similar results have been reported in nodenegative patients. The authors have suggested a lower threshold for lymph node density, but it must be noted that the median number of lymph nodes removed was very low (9) and may represent a more limited lymphadenectomy, whereas a more extended lymph node dissection would have yielded a high lymph node density threshold. Regardless, the concept of an appropriate node dissection is critical in patients undergoing cystectomy for bladder cancer. As previously noted, the presence of LVI has been thought to be of prognostic significance and to provide risk stratification in patients with bladder cancer. Palou and associates20 evaluated 739 patients undergoing radical cystectomy from 1979 to 2002 to determine the impact of LVI in this 226 VOL. 9 NO. 4 2007 cohort. With a mean follow-up of 47 months, LVI was found to correlate to pathologic stage, lymph node involvement, and disease-specific survival. In multivariate analysis, node status and the presence of LVI remained significantly associated with survival. The authors confirm that LVI is a prognostic predictor independent of stage and nodal status following radical cystectomy. In a similar analysis, Luongo and associates21 evaluated the prognostic significance of LVI in 312 patients with TCC of the bladder undergoing radical cystectomy. Overall, 37% of patients were found to have LVI, which was associated with increasing stage, node positivity, grade, and the presence of CIS. Recurrence-free, overall, and disease-specific survival were all significantly lower in patients with LVI. In multivariate analysis, pathologic stage, lymph node, and LVI involvement were all independent prognostic factors for survival following radical cystectomy. These data also add to the growing body of evidence to support the prognostic significance of LVI in patients with invasive bladder cancer. LVI appears be an important risk factor that could better direct adjuvant therapy following surgery for these patients (Table 3). Patients with lymph-node-positive disease are at high risk for recurrence following radical cystectomy. Various factors have been identified to provide risk stratification for these patients. Agarwal and associates22 compared lymph node density and TNM nodal status for predicting diseasespecific survival. Overall, 248 patients with node-positive disease following radical cystectomy were evaluated. No patient received neoadjuvant Table 3 Clinicopathological Features and LVI LVI Negative Age (years) Gender T stage  70 95 62
70 94 61 Male 160 97 Female 29 26  T1 104 6 T2 44 32 T3 38 57 T4 Node stage Grade Carcinoma in situ LVI Positive 3 28 Negative 179 71 Positive 10 52 G1 8 0 G2 8 2 G3 127 113 No CIS 126 99 CIS 63 24 P Value .536 .224 .000 .000 .000 .001 LVI, lymphovascular invasion. Reproduced from Luongo et al21 with permission from the American Urological Association. REVIEWS IN UROLOGY RIU0370_12-12.qxd 12/12/07 8:30 PM Page 227 Best of the 2007 AUA Annual Meeting chemotherapy. With a median followup of 24 months, the median diseasespecific survival at 5 years was 37%. The median number of positive lymph nodes was 2 and the median lymph node density was 20%. The diseasespecific survival for patients with a lymph node density of less than 20% was 55% compared with only a 15% survival at 5 years when the lymph node density was 20% or greater. On univariate analysis, both the TNM system and lymph node density were significant predictors, but only lymph node density remained significant in a multivariate analysis. Other significant factors included adjuvant chemotherapy and organ-confined, lymph node-positive disease. The authors concluded that lymph node density was superior to the TNM staging system for predicting outcomes in node-positive disease following cystectomy, which also appears to be valid in the context of adjuvant chemotherapy. ileal conduit urinary diversion were older. The mean total FACT scores regarding cancer were similar at baseline and 1 year after. Although there was a significant improvement in emotional well-being following treatment, there was a decrease in overall social well-being. There was no obvious difference in HRQOL in these patients stratified by gender and type of urinary diversion. Interestingly, patients with a neobladder had higher HRQOL scores prior to cystectomy compared with ileal conduit patients, but these scores declined at 1 year in the neobladder group and increased in the ileal conduit group. This change was mostly attributed to continence scores. The authors concluded that neobladder patients had a higher diversion. Of 123 patients who underwent radical cystectomy and had 1-year follow-up, 116 patients consented to telephone interviews using validated questionnaires. This included 96 men (82%), of whom 55 (57%) underwent a nerve-sparing cystectomy procedure. With regard to erectile function, men who underwent nerve-sparing procedures and those who were being treated actively for erectile dysfunction scored higher in this domain. During the day, there was no obvious difference in urinary function when comparing the various forms of urinary diversion, whereas night-time urinary function was worse for those undergoing an orthotopic diversion compared with an ileal conduit or continent cutaneous These data suggest that it is important to discuss erectile and urinary issues following cystectomy in all patients regardless of the form of diversion. Patients with erectile dysfunction may improve with treatment, and those with an orthotopic reservoir must recognize the night-time incontinence risk with this form of lower urinary tract reconstruction. Quality of Life Assessing health-related quality of life (HRQOL) following cancer treatments is becoming increasingly more important in the United States. Tikhonenkov and associates23 prospectively assessed HRQOL before and 1 year after radical cystectomy and urinary diversion. A total of 220 patients from 2001 to 2005 were included in the study. A previously validated FACT-Vanderbilt Cystectomy Index (FACT-VCI) was administered and included questions regarding cancer therapy, urinary, bowel, and sexual function. Comparisons were made at baseline and 1 year, and analyzed with respect to age, gender, and type of urinary diversion. Only 94 patients returned the survey at 1 year, a response rate of 42%. The mean age was 68 years, 76% were men, and 47% underwent an orthotopic neobladder. Patients undergoing an baseline HRQOL, likely due to a younger patient population, whereas the decline in QOL scores was mainly due to worsening continence scores 1 year following cystectomy. It may very well be possible that younger patients have higher expectations regarding functional outcomes and HRQOL issues. Thus, despite the fact that neobladder patients do not have a stoma and urostomy bag, they appear less satisfied with the QOL outcomes. Najari and associates24 compared the long-term HRQOL in patients with bladder cancer following radical cystectomy and urinary diversion with regard to erectile, urinary, and bowel function. Patients in this retrospective study underwent various forms of urinary diversion including orthotopic, continent cutaneous, and ileal conduit form of reconstruction. Bowel function was similar in all patients. The authors noted that these data suggest that it is important to discuss erectile and urinary issues following cystectomy in all patients regardless of the form of diversion. Patients with erectile dysfunction may improve with treatment, and those with an orthotopic reservoir must recognize the night-time incontinence risk with this form of lower urinary tract reconstruction. The optimal treatment and management of high-risk T1 bladder cancer is controversial. Immediate cystectomy provides the best chance for cure but is associated with a change in the quality of life. On the contrary, intravesical therapy with a delayed cystectomy is another option that may maintain a similar quality of life VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 227 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 228 Best of the 2007 AUA Annual Meeting continued but with the potential for decreased efficacy. Cost issues, although not primary in the treatment decision process, may also be an important component among patients with bladder cancer, as this is the most expensive malignancy to treat per patient. Kulkarni and associates25 used a Markov Monte Carlo cost effectiveness model to simulate the outcomes of a cohort of patients diagnosed and treated for high-risk grade 3 (G3) T1 bladder cancer. Treatment options include immediate cystectomy versus conservative therapy with intravesical BCG. Using sophisticated probabilistic sensitivity analysis, the researchers found that patients undergoing immediate cystectomy had a higher qualityadjusted life expectancy than those undergoing conservative measures. The expected per patient lifetime cost of immediate cystectomy was $42,400 versus $50,100 for conservative therapy. The authors noted that immediate cystectomy is the dominant treatment for high-risk G3T1 bladder cancer. This treatment scheme could potentially lead to an improved qualityadjusted life expectancy for many patients with this disease and could yield significant cost savings at the societal level. Steiner and associates26 evaluated long-term functional outcomes in women undergoing orthotopic diversion over a 12-year period. All women underwent a T-pouch ileal neobladder, and functional outcomes were evaluated with regard to continence and voiding pattern. The mean age at surgery was 64 years, and the indication for cystectomy was bladder cancer in most patients. Continence was defined as using not more than 1 pad in 24 hours. Although bacteriuria was a common finding, only 13% of patients had symptomatic urinary tract infection. Day and nighttime continence was 81%, and 23% of 228 VOL. 9 NO. 4 2007 women required clean intermittent catheterization to empty the neobladder. These excellent results confirm that this is an appropriate form of reconstruction and arguably should be a standard of care with which other forms of urinary diversion are compared. Institutional and Individual Outcomes It is becoming increasingly evident that hospitals and surgeons performing a high volume of complex urologic procedures are associated with better outcomes following such procedures. Allareddy and Konety 27 sought to determine if hospital volume of radical cystectomy could predict outcomes of other cancer and non-cancer common urologic procedures. A large national database was used (years 2000-2004), and complications following 10 common urologic procedures were not necessarily translate into better outcomes following urologic procedures performed for non-malignant diseases. The use of large national databases has provided important information about various outcomes in patients with bladder cancer following radical cystectomy and has helped to identify risk factors that influence patient morbidity and mortality. Barbieri and associates28 examined the hospital characteristics associated with outcomes following radical cystectomy in patients from a single, highvolume, academic institution as well as a cohort from a nationwide database of academic institutions (University Health System Consortium). From 2002 to 2005, 6728 patients were evaluated from the database and 421 patients from the specific academic center. Overall, the complication rate at the academic center was 32%, average length of stay 7 days, and A greater level of experience with complex urologic procedures such as cystectomy is associated with better outcomes for other urologic procedures performed for malignancy but does not necessarily translate into better outcomes following urologic procedures performed for non-malignant diseases. identified. Hospital volume for cystectomy was characterized as low (1-4/year), medium (5-10/year), or high (
10/year). On multivariate analysis, low cystectomy volume was associated with high odds of complications following other urologic oncologic procedures. There was no significant association between cystectomy volume and reported complications following any of the other non-cancer operations. The authors concluded that a greater level of experience with complex urologic procedures such as cystectomy is associated with better outcomes for other urologic procedures performed for malignancy but does REVIEWS IN UROLOGY in-hospital mortality 1%. The complication rate in the database was 37%, average length of stay 11 days, and in-hospital mortality 1.5%. Institutions that performed more cystectomies (high-volume) had significantly better outcomes than institutions with lower procedure volumes. Hospitals that performed more than 50 cystectomies per year had a mortality rate of only 0.5% compared with almost 3% for institutions that performed 10 or fewer cystectomies per year. The authors concluded that even among academic medical centers, hospitals performing higher volumes of radical cystectomies are associated with improved clinical outcomes, RIU0370_12-12.qxd 12/12/07 8:30 PM Page 229 Best of the 2007 AUA Annual Meeting including decreased mortality and shorter hospital stays. These are important data that may provide a framework for self-assessment and help establish criteria for performance evaluation, but they must be viewed with caution. Many factors influence outcomes following radical cystectomy such as age, associated comorbidities, extent of surgery, and extent of the lymph node dissection, and these may not be factored or evaluated in the database. Regardless, the association of volume and outcomes following cystectomy appears to exist. Existing data support the notion that the more lymph nodes removed and evaluated at cystectomy, the greater the survival advantage conferred in patients with bladder cancer requiring surgery. To analyze this relationship in a slightly different fashion, Hollenbeck and associates29 used the national SEER-Medicare linked database from 1992 to 2003 to evaluate whether hospitals that examined and evaluated more lymph nodes following surgery have superior survival rates. Overall, 3606 patients were studied, with hospitals categorized into 3 evenly sized groups in which 10 or more lymph nodes were removed. After adjusting for differences in patients and providers, high hospital lymph node examination rates were significantly associated with improved overall and cancerspecific survival. These differences were also noted when higher lymph node counts were evaluated. The authors comment that these data provide empirical support for the use of node counts as a proxy for “quality” of surgery. In addition, the data add to the growing body of evidence and underscore the importance not only of node dissection but also of surgical excellence in the treatment of bladder cancer patients requiring cystectomy. As mentioned above, outcomes following radical cystectomy for bladder cancer are dependent on the nodal yield in both lymph-node-positive and node-negative disease. Several variables can influence the nodal counts. Kulkarni and associates30 evaluated the effect of various health care provider characteristics on nodal count at the time of cystectomy. A total of 89 cystectomies were identified between 2001 and 2005, and the impact of surgeon and pathologist was examined. Lymph nodes were evaluated by routine palpation techniques. The median number of nodes identified was 14. On univariate analysis, individual surgeon and the either laparoscopic (n  51) or robotic-assisted (n  60) cystectomy and urinary diversion. The charts were retrospectively evaluated, and various clinical and pathological variables were evaluated. The indication for cystectomy was urothelial cancer in 88% of patients. The average number of lymph nodes removed was 16 in the laparoscopic and 20 in the robotic approach. The overall marginpositive rate was 5.4%. Average hospital stays were 15 days for the laparoscopic approach and 12 days for the robotic, and complication rates were 31% and 33%, respectively. Although the authors state that the minimally invasive approaches can be In general, there does not appear to be any obvious advantage from these minimally invasive approaches for the treatment of invasive bladder cancer and, in fact, they may compromise the oncologic outcomes in these high-risk patients. number of nodal packets submitted were significantly associated with nodal yield. In addition, surgical margins status was associated with nodal counts: fewer nodes were associated with higher positive surgical margins. In multivariate analysis, surgeon and number of node packets remained significant factors with regard to nodal yield. These data confirm the importance not only of the surgeon (who controls for the extent of dissection) but also of how the specimen is submitted to the pathologists. It does not appear that individual pathologists significantly impact nodal yield. Furthermore, it is recommended that a uniform technique, extent of nodal template, and multiple nodal packets improve outcomes and should be advocated in those patients requiring cystectomy for bladder cancer. Technology Lau and associates31 retrospectively reviewed 111 patients undergoing performed for bladder cancer, there are clinical and oncologic concerns. First, the urinary diversions are generally performed extracorporeally, and in many instances continent forms of diversion are not performed. Furthermore, there does not appear to be any benefit with regard to hospital stay with a significant marginpositive rate. In addition, although the authors comment that extended lymphadenectomy was performed, the average number of lymph nodes does not necessarily reflect this. In general, there does not appear to be any obvious advantage from these minimally invasive approaches for the treatment of invasive bladder cancer and, in fact, they may compromise the oncologic outcomes in these high-risk patients. It must be emphasized that minimally invasive approaches must maintain the oncologic principles and provide similar clinical outcomes. It is this reviewer’s opinion that minimally invasive approaches currently are not VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 229 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 230 Best of the 2007 AUA Annual Meeting continued comparable with open radical cystectomy for patients requiring cystectomy for bladder cancer. Guru and associates32 evaluated the feasibility and initial clinical experience in 30 consecutive patients with robotic-assisted radical cystectomy, lymph node dissection, and open urinary diversion for bladder cancer. The mean operative time for the roboticassisted cystectomy was over 3 hours plus an additional 45 minutes spent for a limited (not extended) lymph node dissection. In addition, 155 minutes were then dedicated to the ileal conduit. No patient underwent continent urinary diversion. The mean hospital stay was 9 days. Two patients (6%) had positive surgical margins, and the median number of lymph nodes removed was only 13. The authors concluded that a roboticassisted radical cystectomy and lymph node dissection can be performed safely with good oncologic control. This minimally invasive approach for bladder cancer, in fact, does not provide similar oncologic outcomes, has higher incidence of margin positivity, fewer nodes removed, takes longer surgically, and does not shorten the hospital stay. Feasibility is only appropriate if the approach or technique can replicate the standard—that which is done from an open perspective. It is this reviewer’s strong opinion that the robotic approach does not provide the same oncologic outcomes and has no significant clinical advantages in this oncologic setting of bladder cancer. The use of fluorescence (FL) cystoscopy and the advantages of this technique over traditional white light (WL) cystoscopy in the diagnosis and management of superficial bladder cancer has been a topic of much discussion over the past several years. Penkoff and associates33 reported the results of the first randomized, double-blind, placebo-controlled, multicenter, prospective phase III clinical 230 VOL. 9 NO. 4 2007 trial in which the detection and resection of bladder cancer was evaluated. In this study, 5-ALA induced FL was compared with WL cystoscopy. Patients were randomized and stratified by tumor risk to receive a 3% 5ALA or 0.9% NaCl solution 2 hours before cystoscopy. Endoscopic evaluation and TUR were performed with both FL and WL conditions. Cystoscopy was performed every 3 months. A total of 381 patients were randomized. Patient comparisons revealed a significantly higher proportion of patients with additional CIS lesions detected by FL as compared with WL cystoscopy (54% vs 0%). Tumor documentation revealed 33%, 54%, and 16% of CIS, dysplasia, and Ta lesions detected by FL solely, respectively. Interestingly, when comparing the 140 patients undergoing FL evaluation and the 150 patients undergoing WL cystoscopy with regard to 12-month recurrence-free survival, the researchers found no significant difference between the groups: 62% versus 70%, respectively. Furthermore, this recurrence was independent of the risk group. The au- (CT) scanners in staging the primary bladder tumor, extravesical disease, lymph node metastases, and local tumor extension in bladder cancer patients who subsequently underwent radical cystectomy. A total of 163 patients underwent a preoperative CT scan at least 7 days post TUR of the bladder tumor. The helical CT was 75% accurate in staging perivesical involvement, understaged 15% of the time, and overstaged 10% of the time. Staging results for lymph node metastases were similar: 75% accurate, 15% understaged, and 10% overstaged. Local visceral extension was 90% accurate. Overall, excluding lymph node metastases and distant disease, clinical staging was 56% accurate, with disease understaging at 23%. The authors noted that helical CT scans have improved clinical accuracy in perivesical disease, local extension, and nodal metastases compared with previous published studies using more conventional CT scanners. Despite this improvement, significant inaccuracies remain, and better, possibly molecular, imaging techniques to Fluorescence cystoscopy improved the detection rate of tumor lesions, but this visual improvement does not appear to translate into improved recurrence-free survival rates. thors appropriately noted that FL improved the detection rate of tumor lesions, but this visual improvement does not appear to translate into improved recurrence-free survival rates. White light remains the standard approach, particularly in the United States, for evaluation and detection of bladder tumors, and this traditional technique does not appear to compromise the outcomes of patients with superficial tumors. Diaz and associates34 evaluated the accuracy of multiplanar, multislice (helical) computerized tomography REVIEWS IN UROLOGY improve upon clinical staging and imaging are warranted. Age, Gender, Socioeconomics Although radical cystectomy remains the ideal treatment for invasive bladder cancer, it is less clear if octogenarian patients receive the same benefits of this therapy as younger patients. To examine this question, Chamie and associates35 utilized the SEER data of the National Cancer Institute to compare bladder-preservation (radiation) therapy and radical cystectomy from 1992 to 1997 for RIU0370_12-12.qxd 12/12/07 8:30 PM Page 231 Best of the 2007 AUA Annual Meeting non-metastatic TCC based on various age groups. In this database cohort, 1471 patients underwent radical cystectomy and 1089 underwent radiation therapy. After adjustment for tumor stage and grade, there were significantly improved median overall and cancer-specific survival rates with radical cystectomy for all age groups. Even in the very elderly group (80 to 89 years), the cancer-specific survival was more than double (33 vs 70 months) for cystectomy (Figure 1). These data add to the growing body of evidence that cystectomy remains the ideal therapy for high-grade invasive bladder cancer and may also provide significant benefits for appropriately selected elderly patients. The outcomes of patients with superficial bladder cancer stratified by age groups have not been well studied. Kohjimoto and associates36 assessed the impact of age on recurrence and progression in patients treated for primary superficial bladder cancer. Over a 20-year period (19852005) 491 patients were treated with TUR and/or BCG for superficial bladder cancer. Outcomes were then ana- progression compared with those 60 to 69 years old. The authors note that age appears to be a risk factor that impacts outcomes with bladder cancer even among patients with superficial disease. Although the exact etiology is unknown and, in fact, may involve multiple factors, it is hypothesized that a depressed immune status, an attenuated response to intravesical BCG, and less therapy in this elderly group may all be involved. Alternatively, elderly There is a growing body of evidence to suggest that women have worse oncologic outcomes than men when undergoing therapy for muscle-invasive bladder cancer. The causes of these gender differences are not well defined but may include a delay in diagnosis and possibly technical issues at the time of cystectomy. patients may not be treated as aggressively because of possible health concerns, associated comorbidities, or simply because of their elderly status. Horstmann and associates37 evaluated the gender differences and comparative outcomes in 1269 patients (876 men, 393 women) treated for bladder cancer between 1969 and These data add to the growing body of evidence that cystectomy remains the ideal therapy for high-grade invasive bladder cancer and may also provide significant benefits for appropriately selected elderly patients. lyzed by age groups of less than 50 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, and 80 years or older. The authors found that despite having more so-called broad-based and higher-grade tumors, men in the elderly groups were less likely to be treated with intravesical BCG. Men 80 years or older had the highest recurrence and progression rates among all age groups. In this study, age was found to be an independent risk factor for tumor recurrence in a multivariate analysis. Patients 80 years or older had a 112% higher risk of tumor growing body of evidence to suggest that women have worse oncologic outcomes than men when undergoing therapy for muscle-invasive bladder cancer. The causes of these gender differences are not well defined but may include a delay in diagnosis and possibly technical issues at the time of cystectomy. It is well known that women have a survival advantage in various malignancies, but some studies have sug- 1997 at a single institution. In this retrospective series, men were younger at diagnosis (62 vs 67 years), and had significantly more highgrade and number of tumors. Despite the fact that women had fewer tumors, were older at diagnosis, and had less aggressive tumors, only in the group with muscle-invasive disease did women appear to have significantly worse overall survival (28%) compared with men (33%) at 10 years. Although this study is retrospective, and patients may not have been treated uniformly, there is a gested that women with bladder cancer have a worse prognosis and survival. In order to study these gender differences, Reyblat and associates38 compared the gender outcomes in patients with TCC of the bladder undergoing radical cystectomy at a single institution. A total of 1359 patients (80% men, 20% women) underwent radical cystectomy for TCC of the bladder. Median follow-up was greater than 13 years. There were no apparent gender differences in preoperative therapies, time to cystectomy, pathologic stage and subgroups, margin status, number of lymph nodes removed, and lymph node density. Overall, more women had clinical T3 tumors (19% vs 12%). The overall 5-year recurrence-free survival for women was 61% compared with 70% for men. Women with organ-confined (node-negative) and lymph-nodepositive tumors had significantly worse outcomes compared with men in the same pathologic subgroup. Although overall survival was not different, it was clear that the so-called survival benefit of women with various tumors was not seen in those with VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 231 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 232 Best of the 2007 AUA Annual Meeting continued Figure 1. T3 or lower bladder cancer treated with either radical cystectomy or radiation therapy, stratified by decade of age, diagnosed between 1992 and 1997. NR, not reported. Adapted from Chamie et al 35 with permission from the American Urological Association. Overall Survival Cancer-Specific Survival Age 60–69 1.00 1.00 32 vs 90 months 62 vs NR months 0.75 Odds ratio Odds ratio 0.75 0.50 0.25 0.50 0.25 0 0 0 60 Analysis time (months) 120 0 60 Analysis time (months) 120 Hazard ratio: 2.07 Age 70–79 1.00 1.00 22 vs 57 months 62 vs NR months 0.75 Odds ratio Odds ratio 0.75 0.50 0.25 0.50 0.25 0 0 0 60 Analysis time (months) 120 0 60 Analysis time (months) 120 Hazard ratio: 1.63 Age 80–89 1.00 1.00 16 vs 22 months 33 vs 70 months 0.75 Odds ratio Odds ratio 0.75 0.50 0.25 0.50 0.25 0 0 0 60 Analysis time (months) 120 0 Hazard ratio: 1.23 Cystectomy 232 VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY Radiation 60 Analysis time (months) 120 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 233 Best of the 2007 AUA Annual Meeting bladder cancer requiring cystectomy. In fact, in multivariable analysis in this study, gender differences remained a significant risk factor for recurrence. The rationale for these gender differences is not well elucidated. Regardless, it is apparent that females are at higher risk for disease progression than male patients undergoing radical cystectomy for bladder cancer. Lentz and associates39 evaluated the impact of marital status in patients undergoing radical cystectomy for bladder cancer. It has been observed that married individuals may have improved health status, longer life expectancy, and improved survival in various malignancies compared with unmarried persons. The authors evaluated a cohort of patients undergoing radical cystectomy for bladder cancer and the impact of marital status on demographic, perioperative, and pathologic outcomes in order to better understand the factors that contribute to survival. A total of 204 patients underwent radical cystectomy for transitional cell carcinoma (TCC). Patients were categorized as either married or unmarried (widowed, divorced, or never married). Outcomes were analyzed and compared with various demographic, perioperative, and pathologic factors. Overall, 70% of patients in this cohort were married. Married patients were more often male and had higher body mass index and body fat and significantly lower pre-operative serum creatinine and higher hematocrits. Interestingly, married individuals had shorter mean hospital stays by 1.3 days and had higher rates of organconfined disease with lower rates of lymph node tumor involvement. The authors suggested that these findings support observations in other tumor types and disease states that married patients present earlier than unmarried individuals, which may explain the improved survival outcomes that have been observed. Although not presented, it would be interesting to study the pathologic stage or subgroups and survival outcomes regarding marital status. Regardless, it appears that these data support the concept that married individuals are treated earlier in the bladder cancer disease process compared with unmarried individuals. Manoharan and associates40 analyzed the presentations and outcomes of Hispanic patients undergoing radical cystectomy for bladder cancer. A total of 431 radical cystectomies were performed from 1992 to 2006 at a single institution. Patients were categorized as Hispanic and white nonHispanic, and comparative analysis was performed. Overall, 69 patients (18%) were Hispanic. Hispanic patients presented with higher-stage disease, but there was no significant difference in overall and diseasespecific survival when patients were compared stage for stage. Although the exact reason why Hispanic patients managed with radical cystectomy for bladder cancer present with higher pathologic stage is unknown, it may be related to issues such as access to health care, patient education, and awareness of the signs and symptoms of bladder cancer. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Bartsch G, Hautmann RE, Volkmer BG. Prostate cancer in cystectomy specimens of patients with bladder cancer [abstract 335]. J Urol. 2007;177 [4 suppl]:113. Kefer JC, Liu L, Klein EA, et al. Predicting occult malignancy in the prostate prior to radical cystectomy [abstract 1096]. J Urol. 2007;177[4 suppl]:362. Gupta A, Shariat SF, Nielson M, et al. Outcomes of patients with clinical T1 grade 3 bladder urothelial cell bladder carcinoma treated with radical cystectomy [abstract 1511]. J Urol. 2007; 177[4 suppl]:498-499. Bader P, Spahn M, Woehr M, Frohneberg D. Bladder cancer PT1 G3 N0 M0—results of early cystectomy [abstract 1574]. J Urol. 2007;177[4 suppl]:521. Park J, Song C, You C, et al. Is it always necessary to perform repeat transurethral resection for primary T1G3 bladder cancer absent muscle 16. 17. 18. 19. tissue in the specimen? [abstract 1581]. J Urol. 2007;177[4 suppl]:523. Forster TH, Shahin O, Weltzien B, et al. Prognostic significance of resection biopsy of the tumor bed during TUR-B for superficial transitional bladder cancer [abstract 1586]. J Urol. 2007; 177[4 suppl]:524-525. Hoffmann P, Roumeguère T, Mélot C, et al. Statins are potentially harmful for patients with non-muscle invasive bladder cancer receiving Bacillus Calmette-Guerin [abstract 1567]. J Urol. 2007;177[4 suppl]:518. Thalmann GN, Birkhaeuser F, Rentsch CA, et al. Does the strain of Bacillus Calmette-Guérin (BCG) used for intravesical instillations in the treatment of nonmuscle invasive transitional cell carcinoma of the bladder matter? [abstract 1578]. J Urol. 2007;177[4 suppl]:522. Ali-El-Dein B, Sarhan O, Nabeeh A, et al. Maintenance intravesical BCG therapy for superficial bladder tumors: 3-week multiple courses versus monthly doses [abstract 1579]. J Urol. 2007; 177[4 suppl]:522-523. Hara I, Miyake H, Takenaka A, Fujisawa M. Is second course of BCG instillation therapy effective for bladder carcinoma in situ (CIS)? [abstract 1582]. J Urol. 2007;177[4 suppl]:523. Nativ O, Colombo R, Engelstein D, et al. Combined mitomycin C and hyperthermia (Synergo) for patients with superficial bladder cancer (SBC) after Bacillus Calmette-Guerin (BCG) failure [abstract 1570]. J Urol. 2007;177[4 suppl]:519. Spencer BA, Mohile SG, Hershman D, et al. Adjuvant intravesical therapy and improved survival among elderly patients with superficial bladder cancer [abstract 1571]. J Urol. 2007; 177[4 suppl]:519. Dhar N, Klein EA, Reuther AM, Studer UE. Extended pelvic lymph node dissection is associated with lower recurrence rates in patients after radical cystectomy: a nonrandomized interinstitutional comparison [abstract 334]. J Urol. 2007;177[4 suppl]:113. Hendricksen K, Kiemeney LA, Caris CTM, et al. Recurrence of non-muscle invasive bladder cancer: is it influenced by smoking behavior? [abstract 1084]. J Urol. 2007;177[4 suppl]:358. Agud A, Ribal MJ, Mengual L, et al. Prognostic value of molecular staging of bladder cancer with RT-PCR assay for KRT20: results at 5 year-followup [abstract 1089]. J Urol. 2007;177[4 suppl]:360. Rodriguez O, Palou J, Urdaneta G Jr, et al. An analysis of prognostic factors in patients with PT0 disease following radical cystectomy and long term follow-up [abstract 1514]. J Urol. 2007;177[4 suppl]:499. Colombo R, Briganti A, Sozzi F, et al. Clinical outcome and factors predicting cancer specific survival of patients with PT0 disease following radical cystectomy [abstract 1515]. J Urol. 2007; 177[4 suppl]:499-500. Kunju LP, You L, Zhang Y, et al. Comparison of lymphovascular invasion in TURBT and radical cystectomy specimens from patients with urothelial carcinoma [abstract 1520]. J Urol. 2007;177[4 suppl]:502. Wright JL, Lin DW, Porter MP. The association between extent of lymphadenectomy and survival VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 233 RIU0370_12-12.qxd 12/12/07 8:30 PM Page 234 Best of the 2007 AUA Annual Meeting continued 20. 21. 22. 23. 24. 25. 234 among patients with lymph node metastases undergoing radical cystectomy [abstract 1667]. J Urol. 2007;177[4 suppl]:553. Palou J, Rodríguez O, Algaba F, et al. Disease specific survival is not related to stage in patients with positive lymphovascular invasion in cystectomy specimens [abstract 1664]. J Urol. 2007;177[4 suppl]:552. Luongo T, Ayyathurai R, Nieder AM, et al. Lymphovascular invasion in bladder cancer - is it an important prognostic indicator? [abstract 1665]. J Urol. 2007;177[4 suppl]:552. Agarwal PK, Kassouf W, Dinney CPN, et al. TNM nodal status versus lymph node density for prediction of disease-specific survival after radical cystectomy for bladder cancer [abstract 1663]. J Urol. 2007;177[4 suppl]:551-552. Tikhonenkov SN, Wells N, Dutta S, et al. Prospective assessment of health related quality of life (HRQOL) at one year following radical cystectomy and urinary diversion [abstract 574]. J Urol. 2007;177[4 suppl]:191-192. Najari BB, Hsu EI, Yu RN, et al. Comparing long-term health related quality of life challenges in patients with ileal conduit vs continent cutaneous diversion vs orthotopic neobladder [abstract 1518]. J Urol. 2007;177[4 suppl]:501. Kulkarni GS, Alibhai SMH, Finelli A, et al. Cost effectiveness of treatment strategies for high risk T1G3 bladder cancer [abstract 570]. J Urol. 2007; 177[4 suppl]:190. VOL. 9 NO. 4 2007 26. 27. 28. 29. 30. 31. 32. 33. REVIEWS IN UROLOGY Steiner H, Akkad T, Gozzi C, et al. Long-term functional outcome in orthotopic bladder replacement in women: a single center study [abstract 1655]. J Urol. 2007;177[4 suppl]:549. Allareddy V, Konety BR. Association between post-cystectomy outcomes and complications following other common urologic procedures [abstract 571]. J Urol. 2007;177[4 suppl]:190-191. Barbieri CE, Lee B, Cookson MS, et al. Association of procedure volume with radical cystectomy outcomes in a nationwide database [abstract 1513]. J Urol. 2007;177[4 suppl]:499. Hollenbeck BK, Ye Z, Birkmeyer JD. Lymph node counts and survival following radical cystectomy [abstract 1650]. J Urol. 2007;177[4 suppl]:547. Kulkarni GS, Lockwood GA, Evans A, et al. The effect of health care provider characteristics on nodal yield at radical cystectomy [abstract 1652]. J Urol. 2007;177[4 suppl]:548. Lau CS, Wilson TG, Kawachi MH, et al. Laparoscopic and robotic assisted laparoscopic cystectomy and urinary diversion: the City of Hope experience [abstract 336]. J Urol. 2007;177 [4 suppl]:113. Guru KA, Kim HL, Piacente P, Mohler JL. Robotassisted radical cystectomy and lymph node dissection: initial experience at Roswell Park Cancer Institute [abstract 1649]. J Urol. 2007; 177[4 suppl]:547. Penkoff H, Steiner H, Dajc-Sommerer E, et al. Transurethral detection and resection of bladder carcinomas under white or 5-ALA induced 34. 35. 36. 37. 38. 39. 40. fluorescence light: results of the first doubleblind-placebo controlled clinical trial [abstract 1085]. J Urol. 2007;177[4 suppl]:358. Diaz EC, Miranda G, Boswell W, et al. Accuracy of helical computerized tomography in the clinical staging of bladder cancer [abstract 1659]. J Urol. 2007;177[4 suppl]:550. Chamie K, Hu B, Ellison LM. Cystectomy in the elderly: does the survival benefit in younger patients translate to the octogenarians? [abstract 1516]. J Urol. 2007;177[4 suppl]:500. Kohjimoto Y, Iba A, Shintani Y, et al. Impact of age on outcome of patients with superficial bladder cancer [abstract 1573]. J Urol. 2007; 177[4 suppl]:520-521. Horstmann M, Witthuhn R, Falk M, Stenzl A. Sex specific differences in bladder cancer [abstract 1081]. J Urol. 2007;177[4 suppl]:357. Reyblat P, Sanderson KM, Cai J, et al. Gender differences in the pathologic characteristics and disease specific outcomes in patients with transitional cell carcinoma (TCC) following radical cystectomy [abstract 1510]. J Urol. 2007;177[4 suppl]:498. Lentz A, Sands M, Kouba E, et al. Impact of marital status in patients undergoing radical cystectomy for bladder cancer [abstract 333]. J Urol. 2007;177[4 suppl]:113. Manoharan M, Samavedi S, Ayyathurai R, et al. Radical cystectomy in Hispanic patients: an outcome analysis [abstract 573]. J Urol. 2007;177[4 suppl]:191.