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Purpose: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT., Materials and Methods: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT., Results: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses., Conclusions: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

Background: Radiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC)., Objective: To analyze predictors of complete response (CR) and survival after RT for MIBC., Design, Setting, and Participants: This was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018., Outcome Measurements and Statistical Analysis: Regression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS)., Results and Limitations: The median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3-4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034-0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46-2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25-3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79-3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46-0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51-0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01-1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34-2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17-1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49-0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51-0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12-1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols., Conclusions: RT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation., Patient Summary: We investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare radical prostatectomy outcomes in men with and without exposure to a major infectious event within 30-days of a prior TRUS-biopsy., Materials and Methods: This retrospective cohort study included men who underwent radical prostatectomy from 2002 to 2013 in Ontario, Canada. Several linked administrative databases were used. Exposure was defined as hospitalization with evidence of a urinary tract infection or sepsis during the first 30-days after a prostate biopsy. The primary outcome was a composite of procedures indicative of a likely serious complication of radical prostectomy within the first 12 months after surgery. Secondary outcomes included oncological, functional, and hospital related events within 2 years of radical prostatectomy., Results: A total of 26,254 patients were included in this study and 530 (2.02%) had a post-TRUS-biopsy infection. A similar proportion of patients with and without a post-TRUS-biopsy infectious event experienced the composite primary outcome (1.7% vs 1.1%; odds ratio [OR] 1.61, 95% confidence interval [CI] 0.82-3.14; P = .16). However, exposed patients had significantly higher odds of perioperative blood transfusion (OR 1.61, 95% CI 1.30-2.00; P <.001), bladder neck contracture (OR 1.35, 95% CI 1.12-1.63; P = .002), and 30-day hospital readmission (OR 2.08, 95% CI 1.47-2.95; P <.001), and a small but significant increase in length of hospital stay (P = 0.005). No other significant differences were observed., Conclusion: Although prior infectious events are associated with increased risk of blood transfusion, bladder neck contracture, and hospital readmission following radical prostatectomy, results from this study suggest that major surgical complications, are not adversely affected by TRUS-biopsy related infections., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate the impact of multiple transrectal ultrasound-guided prostate biopsies (TRUS-Bx) before radical prostatectomy (RP) on surgical outcomes., Materials and Methods: Administrative databases were used to identify all patients who had a RP performed in the province of Ontario from April 1, 2002, to March 31, 2013. TRUS-Bx prior to RP were identified and patients were categorized as having one or more than one prior TRUS-Bx. The primary end point was a composite index of serious surgical complications. Secondary outcomes included oncological interventions, functional-related events, and general health service-related outcomes., Results: Among 27,637 patients, 4780 (17.3%) had ≥2 biopsies performed before RP. The proportion of patients who experienced the composite end point was similar between those with one TRUS-Bx compared to those with ≥2 TRUS-Bx (1.05% vs 1.19%, OR 1.14, 95% CI 0.85-1.52). Patients with ≥2 biopsies were more likely to have a perioperative blood transfusion compared to patients with only 1 biopsy (15.5% vs 12.8%, OR 1.25, 95% CI 1.15-1.37), while readmission rate and 30-day mortality were similar. The need for radiotherapy and androgen deprivation therapy within the first year after RP was higher in patients with a single biopsy. Patients with multiple TRUS-Bx were more likely to require post-RP urodynamic evaluation and bladder neck contracture-related interventions but were not at increased odds of surgery for incontinence or erectile dysfunction., Conclusion: Perioperative outcomes after RP are similar between men with single or multiple TRUS-Bx, although multiple TRUS-Bx were associated with an increased odds of perioperative blood transfusion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: This study evaluates the clinical benefit of magnetic resonance-transrectal ultrasound (MR-TRUS) fusion biopsy over systematic biopsy between first-time and repeat prostate biopsy patients with prior atypical small acinar proliferation (ASAP)., Materials: 100 patients were enrolled in a single-centre prospective cohort study: 50 for first biopsy, 50 for repeat biopsy with prior ASAP. Multiparameteric magnetic resonance imaging (MP-MRI) and standard 12-core ultrasound biopsy (Std-Bx) were performed on all patients. Targeted biopsy using MRI-TRUS fusion (Fn-Bx) was performed f suspicious lesions were identified on the pre-biopsy MP-MRI. Classification of clinically significant disease was assessed independently for the Std-Bx vs. Fn-Bx cores to compare the two approaches., Results: Adenocarcinoma was detected in 49/100 patients (26 first biopsy, 23 ASAP biopsy), with 25 having significant disease (17 first, 8 ASAP). Fn-Bx demonstrated significantly higher per-core cancer detection rates, cancer involvement, and Gleason scores for first-time and ASAP patients. However, Fn-Bx was significantly more likely to detect significant cancer missed on Std-Bx for ASAP patients than first-time biopsy patients. The addition of Fn-Bx to Std-Bx for ASAP patients had a 166.7% relative risk reduction for missing Gleason ≥ 3 + 4 disease (number needed to image with MP-MRI=10 patients) compared to 6.3% for first biopsy (number to image=50 patients). Negative predictive value of MP-MRI for negative biopsy was 79% for first-time and 100% for ASAP patients, with median followup of 32.1 ± 15.5 months., Conclusions: MR-TRUS Fn-Bx has a greater clinical impact for repeat biopsy patients with prior ASAP than biopsy-naïve patients by detecting more significant cancers that are missed on Std-Bx.

Background: Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA., Patients and Methods: Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy., Results: PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients., Conclusions: PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Purpose: Ileal conduit (IC) is the most frequent urinary diversion (UD) performed after radical cystectomy (RC). We reviewed the literature to investigate the factors influencing the choice of this diversion and its complications., Methods: A literature search (PubMed) was performed for all English language publications on UDs performed for treatment of bladder cancer from 1950 to 2015. The literature review was focused on studies reporting outcome of IC and its comparison with other types of UDs., Results: IC is the most common UD performed in elderly patients undergoing RC for bladder cancer. Long-term studies looking at the change in renal function after UD report a universal decline in the glomerular filtration rate; however, this decline in renal function is the least for IC. There is a significant morbidity of RC (20-56 %), which can be attributed to patient factors, surgical technique and hospital volume. Modern concepts of bowel preparation, postoperative nutrition, early enteral feeding and involvement of stoma therapists have helped improve the outcomes. The quality of life is preserved, and in many including elderly, it may be improved with IC UD., Conclusions: IC is the most commonly performed UD following radical cystectomy. It is associated with acceptable morbidity and has the lowest reoperation rates as compared to continent diversion. It is also the procedure of choice for most patients' elderly patients as well as patients with limited dexterity, poor motivation, anatomical restrictions and poor renal function. Studies measuring HRQOL report excellent patient acceptability, especially in the elderly population.

Objective: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC., Patients and Methods: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models., Results: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols., Conclusions: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

In the era of managed healthcare, the measuring and reporting of surgical outcomes is a universal mandate. The outcomes should be monitored and reported in a timely manner. Methods for measuring surgical outcomes should be continuous, free of bias and accommodate variations in patient factors. The traditional methods of surgical audits are periodic, resource-intensive and have a potential for bias. These audits are typically annual and therefore there is a long time lag before any effective remedial action could be taken. To reduce this delay the manufacturing industry has long used statistical control-chart monitoring systems, as they offer continuous monitoring and are better suited to monitoring outcomes systematically and promptly. The healthcare industry is now embracing such systematic methods. Radical cystectomy (RC) is one of the most complex surgical procedures. Systematic methods for measuring outcomes after RC can identify areas of improvements on an ongoing basis, which can be used to initiate timely corrective measures. We review the available methods to improve the outcomes. Cumulative summation charts have the potential to be a robust method which can prompt early warnings and thus initiate an analysis of root causes. This early-warning system might help to resolve the issue promptly with no need to wait for the report of annual audits. This system can also be helpful for monitoring learning curves for individuals, both in training or when learning a new technology.

Objective: The purpose of this article is to compare transrectal ultrasound (TRUS) biopsy accuracies of operators with different levels of prostate MRI experience using cognitive registration versus MRI-TRUS fusion to assess the preferred method of TRUS prostate biopsy for MRI-identified lesions. SUBJECTS AND METHODS; One hundred patients from a prospective prostate MRI-TRUS fusion biopsy study were reviewed to identify all patients with clinically significant prostate adenocarcinoma (PCA) detected on MRI-targeted biopsy. Twenty-five PCA tumors were incorporated into a validated TRUS prostate biopsy simulator. Three prostate biopsy experts, each with different levels of experience in prostate MRI and MRI-TRUS fusion biopsy, performed a total of 225 simulated targeted biopsies on the MRI lesions as well as regional biopsy targets. Simulated biopsies performed using cognitive registration with 2D TRUS and 3D TRUS were compared with biopsies performed under MRI-TRUS fusion., Results: Two-dimensional and 3D TRUS sampled only 48% and 45% of clinically significant PCA MRI lesions, respectively, compared with 100% with MRI-TRUS fusion. Lesion sampling accuracy did not statistically significantly vary according to operator experience or tumor volume. MRI-TRUS fusion-naïve operators showed consistent errors in targeting of the apex, midgland, and anterior targets, suggesting that there is biased error in cognitive registration. The MRI-TRUS fusion expert correctly targeted the prostate apex; however, his midgland and anterior mistargeting was similar to that of the less-experienced operators., Conclusion: MRI-targeted TRUS-guided prostate biopsy using cognitive registration appears to be inferior to MRI-TRUS fusion, with fewer than 50% of clinically significant PCA lesions successfully sampled. No statistically significant difference in biopsy accuracy was seen according to operator experience with prostate MRI or MRI-TRUS fusion.

Objective: To evaluate the effect of body mass index (BMI) on the outcomes of patients with urinary tract carcinoma treated with radical surgery., Materials and Methods: Data were collected from 10 Canadian centers on patients who underwent radical cystectomy (RC) (1998-2008) or radical nephroureterectomy (RNU) (1990-2010). Various parameters among subsets of patients (BMI < 25, 25 ≤ BMI < 30, and BMI ≥ 30 kg/m(2)) were analyzed. Kaplan-Meier and multivariate analyses were performed to assess the effect of BMI on overall survival, disease-specific survival, and recurrence-free survival (RFS)., Results: Among the 847 RC and 664 RNU patients, there was no difference in histology, stage, grade, and margin status among the 3 patient subsets undergoing either surgery. However, RC patients with lower BMIs (< 25 kg/m(2)) were significantly older (P = 0.004), had more nodal metastasis (P = 0.03), and trended toward higher stage (P = 0.052). RNU patients with lower BMIs (< 25 kg/m(2)) were significantly older (P = 0.0004) and fewer received adjuvant chemotherapy (P = 0.04) compared with those with BMI ≥ 30 kg/m(2); however, there was no difference in tumor location (P = 0.20), stage (P = 0.48), and management of distal ureter among the groups (P = 0.30). On multivariate analysis, BMI was not prognostic for overall survival, disease-specific survival, and RFS in the RC group. However, BMI ≥ 30 kg/m(2) was associated with more bladder cancer recurrences and worse RFS in the RNU group (HR = 1.588; 95% CI: 1.148-2.196; P = 0.0052)., Conclusions: Increased BMI did not influence survival among RC patients. BMI ≥ 30 kg/m(2) is associated with worse bladder cancer recurrences among RNU patients; whether this is related to difficulty in obtaining adequate bladder cuff in patients with obesity requires further evaluation., (© 2013 Published by Elsevier Inc.)

Objective: To determine the association of gender with outcome after radical cystectomy for patients with bladder cancer., Methods: An observational cohort study was conducted using retrospectively collected data from 11 centers on patients with advanced bladder cancer treated with radical cystectomy. The association of gender with disease recurrence and cancer-specific mortality was examined using a competing risk analysis., Results: The study comprised 4296 patients, including 890 women (21%). The median follow-up duration was 31.5 months for all patients. Disease recurred in 1430 patients (33.9%) (36.8% of women and 33.1% of men) at a median of 11 months after surgery. Death from any cause was observed in 46.0% of men and 50.1% of women. Cancer-specific death was observed in 33.0% of women and 27.2% of men. Multivariable regression with competing risk found that female gender was associated with an increased risk for disease recurrence and cancer-specific mortality (hazard ratio, 1.27; 95% confidence interval, 1.108-1.465; P = .007) compared with male gender. Important limitations include the inability to account for additional potential confounders, such as differences in environmental exposures, treatment selection, and histologic subtypes between men and women., Conclusion: Our analysis identified female gender as a poor-risk feature for patients undergoing radical cystectomy. This adverse prognostic factor was independent of standard clinical and pathologic features and competing risk from non-cancer-related death., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Whether a patient has urothelial carcinoma located within the renal pelvis or ureter remains a controversial prognostic indicator in clinical urology. We wished to evaluate whether tumor location is associated with recurrence in patients undergoing nephroureterectomy for upper tract urothelial cancer in a large volume patient cohort., Subjects and Methods: We created a retrospective database of patients from 7 academic centers throughout Canada who underwent nephroureterectomy for upper tract urothelial carcinoma. Patient demographics as well as pathologic and surgical factors were analyzed to evaluate any statistical association between tumor location and overall survival, disease-free survival, and disease-specific survival., Results: A total of 1,029 patients had data available for analysis with a mean follow up of 3.2 years. Kaplan Meier 5-year disease-free survivals (DFS) were 46%, 37%, and 19% for renal pelvis tumors, ureteric tumors, and multifocal tumors respectively. There was no association between the location of the tumor and the DFS, however, disease involving both the ureter and renal pelvis was associated with lower DFS and overall survival (OS) (P < 0.001)., Conclusions: Tumor location does not appear to have any influence on the risk of recurrence of disease following nephroureterectomy in this large patient cohort. However, multifocal tumors involving both the ureter and renal pelvis had a significantly worse prognosis and should be considered for more aggressive management., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To identify the origin of synchronous and metachronous urothelial carcinoma (UC) of the bladder and upper urinary tract to get a better understanding of the basic mechanism behind the multifocality of UC, which may provide a sound bases for the future development of new strategies for detection, prevention and therapy., Methods: Six patients with UC of the bladder and synchronous or metachronous UC of the upper urinary tract were studied. Genetic analysis involving the study of loss of heterozygosity (LOH) has been evaluated on their tumours using well characterised and new markers of UC (D9S171, D9S177, D9S303 and TP53)., Results: Five of the six patients demonstrated informative results. Four of five (80%) of patients had synchronous or metacharonous UC tumour and showed patterns of LOH consistent with tumorigenesis from monoclonal tumour origin. One of five (20%) patients exhibited a LOH consistent with oligoclonal tumorigenesis., Conclusion: These findings suggest that both the monoclonal and field cancerization theory of tumorigenesis may play a role in tumors of the urothelial tract. However, more data is needed.

Objective: To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer., Methods: From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report., Results: Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not., Conclusion: Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Clinical variables with more accuracy to predict biologically insignificant prostate cancer are needed. We evaluated the combination of transrectal ultrasound-guided biopsy of the prostate (TRUSBx) pathologic and radiologic findings in their ability to predict the biologic potential of each prostate cancer., Materials and Methods: A total of 1043 consecutive patients who underwent TRUSBx were reviewed. Using pathologic criteria, patients with prostate cancer (n = 529) and those treated with radical prostatectomy (RP) (n = 147) were grouped as: "insignificant" (Gleason score ≤ 6, prostate-specific antigen (PSA) density ≤ 0.15 ng/ml, tumor in ≤ 50% of any single core, and < 33% positive cores) and "significant" prostate cancer. TRUSBx imaging and pathology results were compared with the RP specimen to identify factors predictive of "insignificant" prostate cancer., Results: TRUSBx pathology results demonstrated perineural invasion in 36.4% of "significant" versus 5.4% of "insignificant" prostate cancers (p < 0.01) and pathologic invasion of periprostatic tissue in 7% of significant versus 0% of insignificant prostate cancers (p < 0.01). TRUS findings concerning for neoplasia were associated with significant tumors (p < 0.01). Multivariable analysis demonstrated perineural invasion in the biopsy specimen (p = 0.03), PSA density (p = 0.02) and maximum tumor volume of any core (p = 0.02) were independently predictive of a significant prostate cancer., Conclusions: TRUS findings concerning for measurable tumor and perineural invasion in TRUSBx specimens appear to be complementary to Epstein's pathologic criteria and should be considered to aid in the determination whether a prostate cancer is organ-confined and more likely to be biologically insignificant.

Objective: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series., Patients and Methods: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2))., Results: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study., Conclusions: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB., (© 2012 BJU International.)

The overall 5-year survival of patients with urothelial carcinoma of the bladder (UC) is about 78%; however, there are some rare subtypes. One of these is the lipoid cell subtype, which bears a very poor prognosis. Another rare disease entity with a poor prognosis is metastasis to the lower gastrointestinal tract in the form of secondary linitis plastica of the rectum. We describe an extremely rare and unique case of rectal linitis plastica secondary to the rare lipoid cell variant of UC.

Objectives: The role of advanced age as an independent prognostic factor for clinical outcomes after radical cystectomy is controversial. The objective of the current study was to assess the associations between age and clinical outcomes in a large, multi-institutional series of patients treated with radical cystectomy for bladder cancer., Materials and Methods: Institutional radical cystectomy databases containing detailed information on bladder cancer patients treated between 1993 and 2008 were obtained from 8 academic centers in Canada. Data were collected on 2,287 patients and combined into a relational database formatted with patient characteristics, pathologic characteristics, recurrence status, and survival status. Patient age was coded as <60 years, 60-69 years, 70-79 years, or ≥ 80 years. Clinical outcomes were 30-day mortality, 90-day mortality, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). Logistic regression and Cox proportional hazards regression analysis were used to analyze survival data., Results: Five hundred fifty-seven (24.6%), 679 (30.0%), 846 (37.4%), and 181 (8.0%) patients were <60 years, 60-69 years, 70-79 years, and ≥ 80 years, respectively. Increased age was associated with decreased utilization rates of neoadjuvant chemotherapy (P = 0.0143), adjuvant chemotherapy (P < 0.0001), and continent urinary diversion (P < 0.0001) as well as advanced pathologic tumor stage (P = 0.0003), increased positive surgical margins (P < 0.0001), and lymphovascular invasion (P = 0.0335). Compared with patients < 60 years, multivariate regression analysis showed that age ≥ 80 years was independently associated with 90-day mortality (OR 2.98, 95% CI 1.22-7.30), OS (HR 2.03, 95% CI 1.51-2.75), DSS (HR 1.56, 95% CI 1.09-2.24), and RFS (HR 2.06, 95% CI 1.57-2.70)., Conclusions: Age ≥ 80 years at the time of radical cystectomy was independently associated with adverse survival outcomes. These data suggest that increased chronologic age should be considered in clinical trial design and in nomograms predicting survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed., Methods: A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features., Results: The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue., Conclusion: The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease., (Copyright © 2011 Wiley Periodicals, Inc.)

Transrectal ultrasound-guided needle biopsy of the prostate (TRUS) is a well-tolerated and standardized procedure for the diagnosis of prostate cancer. Complications associated with TRUS requiring emergency room visits or hospital admissions are relatively low and include complications, such as a 1% risk of urinary retention and less than 1% chance of bacterial sepsis. Vertebral osteomyelitis is a rare complication of TRUS; there are 3 reported cases. Vertebral osteomyelitis has an insidious onset and usually resolves following medical intervention. We present an extremely rare case of vertebral osteomyelitis following TRUS, its clinical outcome and management.

Background: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated., Objective: To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status., Design, Setting, and Participants: We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe., Measurements: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes., Results and Limitations: The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters., Conclusions: Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors., Methods: We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period., Results: We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma., Conclusion: Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival.

Introduction: Surgical wait times have been shown to be of significance in other malignancies, but limited studies exist in renal cell cancer (RCC). We analyzed surgical waiting time for RCC patients to see if there was an adverse impact on pathological characteristics., Methods: Our centre triages RCC patients on the basis of perceived tumour risk. The waiting time for surgery is adjusted stage for stage: clinical T1 at 90 days, T2 at 40 days, T3 and T4 at 30 days. We retrospectively reviewed the charts of 354 patients who underwent surgery for RCC. Patients were assessed for pathological upstaging, positive lymph nodes, tumour recurrence and tumour size within each stage. Analysis was performed, using surgical waiting time as a categorical variable, to test for associations with disease recurrence or adverse pathological characteristics., Results: The median time from the first consultation to surgery was 41 days and the mean follow-up was 26.6 months. Waiting time stage for stage was: clinical T1 at 57.12 days, clinical T2 at 36.8 days, clinical T3 and T4 at 30.32 days. On multivariate analysis, pathological tumour size was associated with progression, whereas no significant association was found between waiting time and upstaging. Higher stage tumours, sarcomatoid pathology and clinical evidence of progression were associated with shorter waiting times for early interventions., Conclusions: There was no statistically significant evidence for upstaging or progression during the waiting period for our group of patients. The data reinforce previous studies reporting a "safe" period of active surveillance in T1 RCC without affecting their final pathological outcome.

Objective: • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients., Patients and Methods: • The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables., Results: • The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene-directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue-specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag-mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer., (© 2011 American Association for Cancer Research.)

Objective: • To explore the usefulness of cumulative summation (CUSUM) graphs for monitoring positive surgical margin (PSM) rates during a surgeon's transition from open to robot-assisted radical prostatectomy (RARP)., Patients and Methods: • Data were prospectively collected from patients undergoing RARP by a single surgeon. • Preoperatively all patients were either low or moderate risk under the D'Amico classification system. • A CUSUM graph was charted retrospectively to analyse the PSM rate in patients undergoing RARP for pathological stage T2 (pT2) disease. • Acceptable and unacceptable PSM rates were set at 10% and 15% respectively., Results: • From a cohort of 226 patients, 158 patients with pT2 disease were selected. The mean (range) age of these patients was 59.2 (39-73) years, the median (range) Gleason score was 6 (4-9), the mean (range) PSA was 6.43 (0.52-17.5) ng/mL and the mean (range) prostate volume was 44 (18-120) cm(3). In all, 21 patients had PSMs (13%). • CUSUM graphs were produced and clearly demonstrated the change in PSM rate over time., Conclusion: • CUSUM graphs are a novel and useful visual representation of the learning curve for surgeons. • PSM rates in patients with pT2 disease are a good outcome to monitor using CUSUM graphs as they are binary and lack the confounding factors associated with other outcomes such as continence and erectile dysfunction. • We advocate the use of CUSUM graphs as a method of quality assurance with the introduction of a robotics programme., (© 2010 THE AUTHORS; BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Purpose: Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk., Materials and Methods: The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised., Results: Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively., Conclusions: We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system., Methods: We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis., Results: The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival., Interpretation: These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies.

Objective: • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes., Patients and Methods: • Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB., Results: • Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05)., Conclusions: • We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: We present the design, reliability, face, content and construct validity testing of a virtual reality simulator for transrectal ultrasound (TRUS), which allows doctors-in-training to perform multiple different biopsy schemes., Methods: This biopsy system design uses a regular "end-firing" TRUS probe. Movements of the probe are tracked with a micro-magnetic sensor to dynamically slice through a phantom patient's 3D prostate volume to provide real-time continuous TRUS views. 3D TRUS scans during prostate biopsy clinics were recorded. Intrinsic reliability was assessed by comparing the left side of the prostate to the right side of the prostate for each biopsy. A content and face validity questionnaire was administered to 26 doctors to assess the simulator. Construct validity was assessed by comparing notes from experts and novices with regards to the time taken and the accuracy of each biopsy., Results: Imaging data from 50 patients were integrated into the simulator. The completed VR TRUS simulator uses real patient images, and is able to provide simulation for 50 cases, with a haptic interface that uses a standard TRUS probe and biopsy needle. Intrinsic reliability was successfully demonstrated by comparing results from the left and right sides of the prostate. Face and content validity respondents noted the realism of the simulator, and its appropriateness as a teaching model. The simulator was able to distinguish between experts and novices during construct validity testing., Conclusions: A virtual reality TRUS simulator has successfully been created. It has promising face, content and construct validity results.

Purpose: The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival., Materials and Methods: We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic., Results: Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival., Conclusions: Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients., Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC., Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups., Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making., (Copyright © 2011 S. Karger AG, Basel.)

Carcinoma cuniculatum of the penis is an extremely rare variant of squamous cell carcinoma characterized by an endophytic deeply branching and burrowing growth pattern. One documented case series demonstrated afflicted patients ranging in age from 73-83 years with the tumour located on the glans penis, coronal sulcus or foreskin. We report a case of a 55-year-old with disease located on the ventral aspect of the shaft of the penis. The tumour was invasive into the deep dermal connective tissue, comparatively superficial to all previous documented cases. He subsequently underwent a partial penectomy. The case is discussed with a brief review of the literature.

Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting., Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles., Results: The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (> or =T(3)) and nodal involvement., Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.

Purpose: We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome., Materials and Methods: We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe., Results: Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively)., Conclusions: Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder., Materials and Methods: We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen., Results: Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% +/- 0.8% and 69% +/- 0.8% for patients without soft tissue surgical margins vs 21.6% +/- 3.1% and 26.4% +/- 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive., Conclusions: Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy., (Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy., Materials and Methods: The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed., Results: Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173)., Conclusions: Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB)., Patients and Methods: We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space., Results: LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft-tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer-specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node-positive patients, LVI only marginally improved the prediction of cancer-specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%)., Conclusions: LVI is strongly associated with clinical outcome in node-negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.

Purpose: Automatic identification of the biopsy-core tissue location during a prostate biopsy procedure would provide verification that targets were adequately sampled and would allow for appropriate intraprocedure biopsy target modification. Localization of the biopsy core requires accurate segmentation of the biopsy needle and needle tip from transrectal ultrasound (TRUS) biopsy images. A temporal-based TRUS needle segmentation algorithm was developed specifically for the prostate biopsy procedure to automatically identify the TRUS image containing the biopsy needle from a collection of 2D TRUS images and to segment the biopsy-core location from the 2D TRUS image., Methods: The temporal-based segmentation algorithm performs a temporal analysis on a series of biopsy TRUS images collected throughout needle insertion and withdrawal. Following the identification of points of needle insertion and retraction, the needle axis is segmented using a Hough transform-based algorithm, which is followed by a temporospectral TRUS analysis to identify the biopsy-needle tip. Validation of the temporal-based algorithm is performed on 108 TRUS biopsy sequences collected from the procedures of ten patients. The success of the temporal search to identify the proper images was manually assessed, while the accuracies of the needle-axis and needle-tip segmentations were quantitatively compared to implementations of two other needle segmentation algorithms within the literature., Results: The needle segmentation algorithm demonstrated a >99% accuracy in identifying the TRUS image at the moment of needle insertion from the collection of real-time TRUS images throughout the insertion and withdrawal of the biopsy needle. The segmented biopsy-needle axes were accurate to within 2.3 +/- 2.0 degrees and 0.48 +/- 0.42 mm of the gold standard. Identification of the needle tip to within half of the biopsy-core length (<10 mm) was 95% successful with a mean error of 2.4 +/- 4.0 mm. Needle-tip detection using the temporal-based algorithm was significantly more accurate (p < 0.001) than the other two algorithms tested, while the segmentation of the needle axis was not significantly different between the three algorithms., Conclusions: The temporal-based needle segmentation algorithm accurately segments the location of the biopsy core from 2D TRUS images of clinical prostate biopsy procedures. The results for needle-tip localization demonstrated that the temporal-based algorithm is significantly more accurate than implementations of some existing needle segmentation algorithms within the literature.

Purpose: To compare the accuracy of biopsy with two-dimensional (2D) transrectal ultrasonography (US) with that of biopsy with conventional three-dimensional (3D) transrectal US and biopsy with guided 3D transrectal US in the guidance of repeat prostate biopsy procedures in a prostate biopsy simulator., Materials and Methods: The institutional review board approved this retrospective study. Five residents and five experts performed repeat biopsies with a biopsy simulator that contained the transrectal US prostate images of 10 patients who had undergone biopsy. Simulated repeat biopsies were performed with 2D transrectal US, conventional 3D transrectal US, and guided 3D transrectal US (an extension of 3D transrectal US that enables active display of biopsy targets). The modalities were compared on the basis of time per biopsy and how accurately simulated repeat biopsies could be guided to specific targets. The probability for successful biopsy of a repeat target was calculated for each modality., Results: Guided 3D transrectal US was significantly (P < .01) more accurate for simulated biopsy of repeat targets than was 2D or 3D transrectal US, with a biopsy accuracy of 0.86 mm +/- 0.47 (standard deviation), 3.68 mm +/- 2.60, and 3.60 mm +/- 2.57, respectively. Experts had a 70% probability of sampling a prior biopsy target volume of 0.5 cm(3) with 2D transrectal US; however, the probability approached 100% with guided 3D transrectal US. Biopsy accuracy was not significantly different between experts and residents for any modality; however, experts were significantly (P < .05) faster than residents with each modality., Conclusion: Repeat biopsy of the prostate with 2D transrectal US has limited accuracy. Compared with 2D transrectal US, the biopsy accuracy of both experts and residents improved with guided 3D transrectal US but did not improve with conventional 3D transrectal US.

Intravesical chemotherapy after transurethral resection of a bladder tumour (TURBT) has been observed to significantly decrease recurrence rates compared to TURBT alone. Though immediate postoperative intravesical treatment with chemotherapeutic agents after transurethral resection for superficial bladder carcinoma is generally considered a safe and effective adjunctive therapy in decreasing recurrence rates, its instillation is not always completely innocuous. Lately, a more serious complication of bladder perforation associated with immediate instillation of intravesical mitomycin C (MMC) after TURBT was reported. We report our own experience of a male patient with bladder perforation after an early instillation of a single dose of MMC. In this case, systemic toxicity occurred which required intensive care after surgical repair.

Background: Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder (UCB), with its variable behaviour, represents one of the most difficult challenges for urologists and patients alike., Objective: To evaluate the characteristics and long-term outcome of patients with clinical T1G3 UCB treated with radical cystectomy (RC)., Design, Setting, and Participants: Data from 1136 patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy were collected at 12 centres located in Europe, the United States, and Canada. Median age was 67 yr (range: 29-94), with a male-to-female ratio of 4:1., Measurements: Patients' characteristics and outcome are evaluated., Results and Limitations: Of the 1136 patients, 33.4% had non-organ-confined stage at cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3. Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB., Conclusions: Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC., (Copyright 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)