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Sex cord-stromal tumors are the second most common testicular tumors after germ cell tumors. They account for about 2%–5% of adult testicular tumors. Most of these tumors are benign. The most common sex cord-stromal tumor is Leydig cell tumor. In contrast, testicular fibroma is a very rare type of sex cord-stromal tumors. Histologically, testicular fibromas resemble their ovarian counterparts; however, they are much less common than ovarian fibromas. To the best of our knowledge

This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with renal cell carcinoma (RCC). It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and healthcare policy makers in the management of patients diagnosed with RCC.

This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with prostate cancer. It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi oncology society and Saudi urological association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with adenocarcinoma of the prostate to.

This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with renal cell carcinoma (RCC). It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and healthcare policy makers in the management of patients diagnosed with RCC.

O1: Assessing the protective effect of dexrazoxane against doxorubicin-induced toxicity in HL-1 cardiomyocytes

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The stakes are high when making treatment decisions in T1 bladder cancer (BC). Conservative management may lead to progression and possibly death from BC. Conversely, radical cystectomy could be over-treatment of non-progressive disease. The problem for clinicians is that reliable prognostic indices are lacking. We performed a head-to-head comparison of two substaging systems, European Organisation for the Research and Treatment of Cancer (EORTC) risk scores and four molecular markers in T1 carcinomas of the bladder treated conservatively with BCG. T1 sub-stage according to a new system (micro-invasive [T1m] and extensive-invasive [T1e]) was the most important clinical variable for predicting progression to carcinoma invading bladder muscle. The performance of the EORTC risk scores was disappointing for this T1 sub-group. Molecular markers were not significant in multivariable analysis for predicting progression. Future studies may lead to the incorporation of sub-stage (T1m/T1e) in the TNM classification system for urinary BC to guide clinical decision-making in T1 BC. OBJECTIVE To evaluate the prognostic significance of four molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer (EORTC) risk scores in primary T1 bladder cancer (BC) treated with adjuvant bacille Calmette-Guerin. PATIENTS AND METHODS The slides of 129 carcinomas of the bladder from two university hospitals were reviewed and the T1 diagnosis was confirmed. T1 sub-staging was done in two separate rounds, using a new system that identifies micro-invasive (T1m) and extensive-invasive (T1e) T1BC, and then according to invasion of the muscularis mucosae (T1a/T1b/T1c). The EORTC risk scores for recurrence and progression were calculated. Uni- and multivariable analyses for recurrence and progression were performed using clinicopathological variables, T1 sub-stage, EORTC risk scores and molecular markers (fibroblast growth factor receptor 3 gene mutation and Ki-67, P53, P27 expression). RESULTS The median follow-up was 6.5 years. Forty-two patients remained recurrence-free (33%). Progression to T2 or metastasis was observed in 38 (30%) patients. In multivariable analysis for recurrence, multiplicity was significant. In multivariable analysis for progression, female gender, sub-stage (T1m/T1e) and carcinoma in situ (CIS) were significant. Molecular markers were significant in univariable and in multivariable analyses for recurrence. EORTC risk scores were not significant. CONCLUSIONS CIS, female gender and sub-stage (T1m/T1e) were the most important variables for progression. The additional value of molecular markers was modest. Sub-stage (T1m/T1e) could potentially be incorporated in future tumour-node-metastasis classifications.

Study Type – Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Smoking is well described among the most important risk factors for bladder cancer. It is also known that higher quantity of tobacco exposure is associated with higher bladder cancer risk and that smoking cessation is known to be associated with lower risk of bladder cancer. Furthermore, among patients with non-muscle invasive bladder cancer, smoking cessation decreases the risk of tumour recurrence. On the other hand, the effect of smoking on tumour stages at presentation and especially on prognosis is not well studied. The current study describes the presentation and outcome of 564 patients (64% smokers, 36% non-smokers) treated with radical cystectomy. Patients with smoking history have more advanced outcome at the time of radical surgery and significantly worse outcome after surgery when compared to non-smokers, although the effect of smoking was not significant when survival was studied in multivariable analysis including classic prognostic parameters such as tumour grade, stage and adjuvant chemotherapy. Finally, there was a surprising finding that history of smoking affected outcome among male patients but such effect was not noted among female patients. OBJECTIVE • To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population. PATIENTS AND METHODS • A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. • In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. • Categorical data were analyzed by the chi-squared test and numerical data were analyzed by Student's t-test. • The Kaplan–Meier method, log-rank test and a proportional hazards model were used to estimate the effect of smoking on survival. RESULTS • In total, 352 patients (64%) were smokers and 194 (36%) were non-smokers. • Smokers had more frequently advanced tumours and nodal metastasis. • The 10-year disease-specific survival (DSS) was 52% vs 66% for smokers and non-smokers, respectively (P= 0.039). • Smokers also had significantly worse overall survival (10-year overall survival 37% vs 62%; P= 0.015). • Smoking affected significant DSS among men (P= 0.012), although no effect was observed among women. • In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0–1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1–1.8) for overall mortality. • In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8–1.6; P= 0.41). • In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1–2.3; P= 0.007). CONCLUSIONS • Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. • Smoking affected survival only among men. • Women had poorer survival but smoking was not a contributing factor to this.

Background and Objectives: To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy. Materials and Methods: This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. Results: Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values

Study Type – Prognosis (multi-centre cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? More men than women develop bladder cancer (BC) but reasons why are unclear. Recent findings have implicated androgens, androgen receptors (AR) and AR expression in BC. Previous studies showed that a significant loss of AR expression was associated with aggressive BC. However, these results have been gathered on limited series of patients. We analyzed the expression of AR in BC and its correlation with gender, grade, stage and clinical outcome on a large multi-institutional (Toronto/Dallas) cohort. In contrast to previous reports, our data do not suggest that loss of AR expression is gender-related nor associated with invasive BC. In fact, in this large cohort, we showed that AR positivity is actually uncommon in BC, that there are no differences in expression among high and low grade tumours and no statistically significant differences between muscle-invasive AR-positive and AR-negative cases in time to death, or time to recurrence. OBJECTIVE • To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. PATIENTS AND METHODS • A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA. RESULTS • The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases. CONCLUSION • In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC.

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? High-grade non muscle invasive bladder cancer is a very aggressive disease, potentially lethal if not managed adequately, because of the ability of these tumours to invade surrounding tissues and become metastatic. Treatment with intravesical BCG has been shown to delay progression to muscle invasive or/and metastatic disease, preserve the bladder, and decrease the risk of death from bladder cancer. However, most studies have analyzed patients with short follow-up, and long-term data about the real efficacy of BCG to prevent tumour recurrence, progression and impact mortality are lacking. This study has analyzed a large series of patients with high-grade non muscle invasive bladder cancer treated with intravesical BCG in two University Institutions (Toronto and Rotterdam), with a central pathology review by a very experienced uro-pathologist. It provides further insight into the long-term risks of progression of patients harbouring high-grade T1 bladder cancer treated with BCG, demonstrating that about 30% of patients are at risk of progression and that late progressions even more than 3 years after the initial resection and BCG treatment are rare but not exceptional. OBJECTIVE To report the long-term results of bacille Calmette-Guerin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high-grade (HG) bladder cancer (BC) confirmed by central pathological review. PATIENTS AND METHODS In all, 136 patients from two university centres (Rotterdam, n= 49; Toronto, n= 87) were diagnosed with primary T1HG BC. One experienced uro-pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models. RESULTS Mean (range) follow-up was 6.5 (0.3–21.6) years. There were no significant differences for recurrence (P= 0.52), progression (P= 0.35) and disease-specific survival (DSS) (P= 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow-up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P= 0.011). No independent predictors were found for progression. CONCLUSIONS Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥3 years after BCG. Caution should be exercised when relying on the long-term effects of BCG, and close follow-up of these patients should not be neglected.

This is an update to the previously published Saudi guidelines for the evaluation and medical/surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The guidelines are presented with their accompanying supporting evidence level, which is based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

This is an update to the previously published Saudi guidelines for the evaluation and medical and surgical management of patients diagnosed with prostate cancer. Prostate cancer is categorized according to the stage of the disease using the tumor node metastasis staging system 7th edition. The guidelines are presented with supporting evidence levels based on a comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Local factors, such as availability, logistic feasibility, and familiarity of various treatment modalities, have been taken into consideration. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with adenocarcinoma of the prostate.

Background: Since the introduction of nerve-sparing radical prostatectomy (NSRP), there have been concerns about the increased risks of positive surgical margins (PSM) and biochemical progression (BP). We examined the relationship of NSRP with PSM and BP using a large, mature dataset. Materials and Methods: Patients who underwent RP for clinically localized prostate cancer at our center between 1997 and 2008 were identified. Patients who received neoadjuvant therapy were excluded. We examined the relation of NSRP to the rate of PSM and BP in univariate and multivariate analyses adjusting for clinical and pathological variables including age, pretreatment prostate-specific antigen (PSA) levels and doubling time, and pathological stage and grade. Results: In total, 856 patients were included, 70.9% underwent NSRP and 29.1% had non-NSRP. PSM rates were 13.5% in the NSRP group compared to 17.7% in non-NSRP ( P =0.11). In a multivariate analysis, non-NSRP was preformed in patients with a higher pathological stage (HR 1.95, 95% CI 1.25-3.04, P =0.003) and a higher baseline PSA level (HR 1.04, 95% CI 1.01-1.08, P =0.005). With a median follow-up of 41 months, BP-free survival was 88% for non-NSRP compared to 92% for the NSRP group (log rank P =0.018); this difference was not significant in a multivariate Cox regression analysis (HR 0.54, 95% CI 0.28-1.06, P =0.09). Conclusion: When used in properly selected patients, NSRP does not seem to increase the risk of PSM and disease progression. The most effective way of resolving this issue is through a randomized clinical trial; however, such a trial is not feasible.

BJU Int 2010; 106: 206–211. Objective: To evaluate the effect of a pathology review on the clinical outcome of patients with primary pT1 bladder cancer (BC), as the clinical course of such patients is variable. Patients and Methods: The slides of 164 primary (first diagnosis) pT1 bladder tumours from two university hospitals were reviewed by one pathologist for stage and grade (World Health Organization 1973 and 2004). Patients were initially managed conservatively with bacille Calmette-Guerin (BCG). Uni- and multivariate analyses compared the predictive value of age, gender, hospital, carcinoma in situ (CIS), tumour-size, reviewed grade and reviewed stage. Results: With a mean follow-up of 6.4 years, there was disease progression in 48 (29%) patients and 26 (16%) died from BC. Associated CIS was found in 55 (34%) patients. After reviewing the slides, 24 (15%) tumours were downstaged to pTa, 134 (82%) remained pT1 and six (4%) were upstaged to or pT2. The grade review resulted in 74 G2, 90 G3, 37 low-grade and 127 high-grade lesions for the two systems used. In multivariate analyses, reviewed stage (both P 0.001) and CIS (P 0.017 and 0.023) had independent significance for progression and disease-specific survival, respectively. Conclusion: A stage review is indicated in pT1 BC, as almost 20% of pT1 tumours were up- or downstaged, and the reviewed stage predicted the patient’s prognosis. Hence, pathology review identified patients with different prognoses who might benefit from other treatment strategies than BCG. We confirmed that CIS is an unfavourable sign in pT1 bladder cancer. Editorial Comment: This article is unique in that instead of evaluating whether review of cases from a community hospital is beneficial, the authors reviewed cases from 2 major universities with expertise in urological pathology. Of T1 tumors 20% were either upstaged or down-staged, and the reviewed stage was an independent predictor of disease specific survival. It appears that even if an expert pathologist reads a case, review of all T1 tumors by more than 1 pathologist is important.

Background: Management of T1 bladder cancer (BCa) is controversial. Objective: Evaluate the impact of substage on the clinical outcome of T1 BCa. Design, setting, and participants: The T1 diagnosis of 134 first-diagnosis BCa patients from two university hospitals was confirmed. For the T1 substage, we used a new system that discerns T1-microinvasive (T1m) and T1-extensive-invasive (T1e) tumors. We then determined the invasion of the muscularis mucosae-vascular plexus (MM-VP): T1a (invasion above the MM-VP), T1b (invasion in the MM-VP), or T1c (invasion beyond the MM-VP). If the MM-VP was not present at the invasion front, the case was assigned to T1a or T1c. All patients were initially managed conservatively (with bacillus Calmette-Guerin). Measurements: Multivariable analyses for progression and disease-specific survival (DSS). Results and limitations: Median follow-up was 6.4 yr (interquartile range: 3.3-9.2 yr). Progression to >= T2 was observed in 40 patients (30%), and 19 patients (14%) died of BCa. The MM-VP was not present at the invasion front in 50 patients (37%). T1 substage was as follows: 40 T1m and 94 T1e; 81 T1a, 18 T1b, and 35 T1c. In multivariable analyses, substage (T1m/T1e) was significant for progression (p = 0.001) and DSS (p = 0.032), whereas substage according to T1a/T1b/T1c was not significant. Female gender (p = 0.006) and carcinoma in situ (p = 0.034) were also significant predictors of progression. Themainlimitation to the study is absence of a repeat transurethral resection. Conclusions: Substage according to the new system (T1m and T1e) was user-friendly, possible in 100% of cases, and very predictive of T1 BCa behavior. Future studies may ultimately lead to the incorporation of this new substaging system in the TNM classification system for urinary BCa. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population.A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. Categorical data were analyzed by the chi-squared test and numerical data were analyzed by Student's t-test. The Kaplan-Meier method, log-rank test and a proportional hazards model were used to estimate the effect of smoking on survival.In total, 352 patients (64%) were smokers and 194 (36%) were non-smokers. Smokers had more frequently advanced tumours and nodal metastasis. The 10-year disease-specific survival (DSS) was 52% vs 66% for smokers and non-smokers, respectively (P = 0.039). Smokers also had significantly worse overall survival (10-year overall survival 37% vs 62%; P = 0.015). Smoking affected significant DSS among men (P = 0.012), although no effect was observed among women. In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0-1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1-1.8) for overall mortality. In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8-1.6; P = 0.41). In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1-2.3; P = 0.007).Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. Smoking affected survival only among men. Women had poorer survival but smoking was not a contributing factor to this.

• Many experts consider that media coverage, marketing and/or direct-to-consumer advertising, particularly Internet-based forms, are fundamental to the widespread adoption of robotic-assisted prostatectomy (RARP). However, this has not been explored previously. • The primary objective of the present study was to delineate the role of media coverage and marketing of RARP on the Internet, whereas the secondary goal focused on website quality with respect to the presentation of prostatectomy.• Website content was evaluated for direct-to-consumer advertising after the retrieval of the first 50 websites using Google and Yahoo for each of the terms: 'robotic prostatectomy, laparoscopic prostatectomy (LP) and open radical prostatectomy (ORP)'. • A linear regression analysis was performed for the annual number of Internet news hits over the last decade for each procedure. Website quality assessment was performed using WHO Honesty on the Internet (HON) code principles.• Of the retrieved sites, the proportion containing direct-to-consumer advertising for RARP vs LP vs ORP using Google was 64% vs 14% vs 0%, respectively (P0.001) and, using Yahoo, 80% vs 16% vs 0%, respectively (P0.001). • In a linear regression analysis, the r(2) values for news hits for each year over the last 10 years were 0.89, 0.74 and 0.76 for RARP, LP and ORP, respectively. • Website quality assessment found that a minority of the websites were accredited with HONcode principles, with no difference between procedure types (P0.05).• Media coverage and marketing of RARP on the Internet is more widespread compared to LP and ORP. • Disturbingly, the quality of websites using any technique for prostatectomy was of poor quality when using principles of honest information presenting and such findings need to be discussed with respect to obtaining informed consent from patients.

To report the long-term results of bacille Calmette-Guérin (BCG) intravesical therapy in relation to disease progression and recurrence in primary T1 high-grade (HG) bladder cancer (BC) confirmed by central pathological review.In all, 136 patients from two university centres (Rotterdam, n = 49; Toronto, n = 87) were diagnosed with primary T1HG BC. One experienced uro-pathologist reviewed all slides, ensuring all cases were indeed HG and that muscle was present in all specimens. Patients were treated with BCG induction (six instillations) after transurethral resection (TUR) of the tumour and followed with cystoscopy and urinary cytology. Predictors for recurrence, progression and survival were assessed with multivariable Cox regression models.Mean (range) follow-up was 6.5 (0.3-21.6) years. There were no significant differences for recurrence (P = 0.52), progression (P = 0.35) and disease-specific survival (DSS) (P = 0.69) between the two centres. Among the cohort, 47 patients (35%) recurred and 42 (30.9%) progressed with a median time to progression of 2.1 years; 16 (38%) of these progressions occurred ≥ 3 years after the initial BCG course; 22 (16%) patients who progressed died from BC. Overall, 96 (71%) patients had no evidence of disease at the last follow-up. Carcinoma in situ was the only independent predictor for recurrence in multivariate analysis (P = 0.011). No independent predictors were found for progression.Conservative treatment with BCG is a valid option in primary T1HG BC. Nevertheless, the aggressive nature of T1HG BC is evident in the fact that 30% progressed, with a high proportion of these progression events occurring ≥ 3 years after BCG. Caution should be exercised when relying on the long-term effects of BCG, and close follow-up of these patients should not be neglected.

Background More than 25% of bladder cancer (BC) cases are still muscle-invasive at first diagnosis. Screening is unproven to enable the detection of more non–muscle-invasive tumors. BC association with aristolochic acid nephropathy (AAN) was reported after intake of slimming pills containing Chinese herbs. Objective We evaluated whether a BC screening protocol in a high-risk and unique patient population had an impact on the stage of tumor presentation. Design, setting, and participants Forty-eight AAN-affected patients were enrolled in a screening program, establishing BC incidence during prospective screening cystoscopies and biopsies biannually for up to 10 yr. Two patients were lost to follow-up, and three refused screening after consenting. Measurements Patients were evaluated for presence of BC and tumor stage at diagnosis. Results and limitations BC was diagnosed in 25 patients (52%). Among 43 patients who underwent screening cystoscopies (median follow-up: 94 mo), 22 were first diagnosed with non–muscle-invasive BC but none with muscle-invasive tumors and none died of BC. Three women who declined follow-up were diagnosed and died with advanced metastatic disease. The limitations of our findings include the small sample size of this case series, the absence of a real control group, and the particular risk factor in these patients that differs from the usual risk factors, such as smoking or industrial chemicals. Conclusions BC screening in high-risk groups may allow identification of tumors before muscle invasion. The optimal screening schedule and the relevance of the present findings in smoking-related BC remain to be defined.

T1 high-grade (formerly T1G3) bladder cancer is a challenging clinical entity representing approximately 10-15% of all new bladder cancer cases. The variable natural history of the disease and possible impairment in quality of life associated with radical treatment makes T1 high-grade one of the most challenging uro-oncological patient groups to manage. In particular, the risk of clinical understaging and not recognizing muscle-invasive disease may have detrimental effects on patient outcome. The cornerstone of contemporary staging is restaging transurethral resection (TUR), which helps in defining further management. In patients with restaging TUR stage less than T1, induction bacillus Calmette-Guerin combined with maintenance offers good results. The option of radical cystectomy should be discussed with patients with restaging TUR stage T1 or higher and it is highly recommended to all patients with recurrent T1 of carcinoma in situ during bacillus Calmette-Guerin maintenance. In addition to restaging TUR stage, several other clinicopathological factors, such T1 substaging, associated carcinoma in situ, tumor size and appearance, lymphovascular invasion, and hydronephrosis, aid in the decision making between radical and conservative treatment. Future prospects include improved staging and molecular markers that may guide toward conservative therapy or allow more cT1 patients to be offered nerve-sparing cystectomies and neobladders and, thus, improving quality of life for patients undergoing radical surgery.

• To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC.• A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA.• The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases.• In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC.

To evaluate the effect of a pathology review on the clinical outcome of patients with primary pT1 bladder cancer (BC), as the clinical course of such patients is variable.The slides of 164 primary (first diagnosis) pT1 bladder tumours from two university hospitals were reviewed by one pathologist for stage and grade (World Health Organization 1973 and 2004). Patients were initially managed conservatively with bacille Calmette-Guérin (BCG). Uni- and multivariate analyses compared the predictive value of age, gender, hospital, carcinoma in situ (CIS), tumour-size, reviewed grade and reviewed stage.With a mean follow-up of 6.4 years, there was disease progression in 48 (29%) patients and 26 (16%) died from BC. Associated CIS was found in 55 (34%) patients. After reviewing the slides, 24 (15%) tumours were downstaged to pTa, 134 (82%) remained pT1 and six (4%) were upstaged toor =pT2. The grade review resulted in 74 G2, 90 G3, 37 low-grade and 127 high-grade lesions for the two systems used. In multivariate analyses, reviewed stage (both P0.001) and CIS (P = 0.017 and 0.023) had independent significance for progression and disease-specific survival, respectively.A stage review is indicated in pT1 BC, as almost 20% of pT1 tumours were up- or downstaged, and the reviewed stage predicted the patient's prognosis. Hence, pathology review identified patients with different prognoses who might benefit from other treatment strategies than BCG. We confirmed that CIS is an unfavourable sign in pT1 bladder cancer.

Few studies have examined the prognostic significance of prior tumor resection(s) in cases of T1 nonmuscle invasive bladder cancer treated with intravesical bacillus Calmette-Guerin. We examined this issue by comparing the prognosis of primary vs nonprimary T1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.Patients with pT1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin were identified and tumor pathology was reviewed. Patients were then stratified into primary vs nonprimary tumors, and outcomes were compared using univariate, multivariate and Kaplan-Meier survival analyses, and the Cox regression model adjusting for various clinical and pathological features including, age, gender, tumor size, multifocality, pathological grade and associated carcinoma in situ.The study included 191 patients, 95 (49.7%) with primary and 96 (50.3%) with nonprimary tumors. The clinical and pathological characteristics were comparable. For the primary vs the nonprimary group progression rates were 24.2% vs 39.6%, respectively (HR 2.07, 95% CI 0.98-3.71, multivariate p = 0.03) and the 5-year progression-free survival rates were 71.9% vs 51.5%, respectively (log rank p0.001). This difference remained significant on multivariate Cox regression analysis (HR 2.53, 95% CI 1.40-4.57, p = 0.002). There was no difference between the groups in recurrence or disease specific mortality.Nonprimary T1 nonmuscle invasive bladder tumors treated with bacillus Calmette-Guerin carry a significantly higher risk of progression to muscle invasive disease compared to primary tumors. This information may be used in combination with other prognostic factors to identify those at high risk for progression when counseling patients.

Positive surgical margins have a negative impact on disease outcomes after radical prostatectomy, yet their prognostic value may vary depending on specific pathological characteristics. We examined the relationship of positive surgical margins to biochemical progression according to several clinicopathological features.We analyzed data from 1,268 patients who underwent radical prostatectomy for clinically localized prostate cancer at our center between 1992 and 2008, and did not receive any neoadjuvant or adjuvant treatment. We examined the relation of age, pretreatment prostate specific antigen, pathological T stage, radical prostatectomy Gleason score, disease risk group and surgical margin status to biochemical progression-free survival.The overall positive surgical margin rate was 20.8% and median followup was 79 months. The impact of positive surgical margins was dependent on risk group. Biochemical progression-free survival was 99.6% for the negative surgical margin group vs 94.9% for the positive surgical margin group in low risk disease (log rank p = 0.53), 93.5% for the negative surgical margin group vs 83% for the positive surgical margin group in intermediate risk disease (log rank p0.001) and 78.5% for the negative surgical margin group vs 57.1% for the positive surgical margin group in high risk disease (log rank p = 0.003). These differences remained significant in a multivariate Cox regression model adjusting for other clinicopathological features.Positive surgical margins are an independent predictor of biochemical progression in patients with intermediate and high risk prostate cancer. Patients with low risk disease have a favorable long-term outcome regardless of margin status and may be candidates for expectant management even with positive surgical margins, sparing them the side effects and costs of treatment.

Bacille Calmette-Guérin (BCG) is recommended as adjunctive therapy among patients with high-risk nonmuscle-invasive bladder cancer (BC). Given that immune response is attenuated with age, we set out to determine the impact of age on response to BCG.We searched our prospective bladder information system and limited our search to patients with incident BC completely resected at transurethral resection (TUR) who completed a full induction course of BCG. We then analyzed the impact of age on outcome. Age was analyzed both dichotomously (greater or less than 75 years) as well as by 10-year increments. The main outcomes were recurrence or progression-free survival. Log-rank and multivariable Cox proportional-hazard analyses, adjusting for clinical and pathologic features (age, multifocality, pathologic stage, grade and associated carcinoma in situ, maintenance, and restaging) were used.This cohort included 238 patients. Baseline parameters were similar aside from tumor number. Progression-free survival differed between age groups when examined either dichotomously or via 10-year increments. The 2-year progression-free survival was 87% among patients75 years vs 65% in patients75 years (log rank P.001). An age-dependent trend was noted when analyzed by 10-year increment (log-rank for trend P = .011). On multivariable analysis, age was an independent risk factor for progression (HR = 2.9, 95% CI 1.7-4.9). Recurrence-free survival was similar among age strata.We demonstrated that advanced age is associated with higher progression rates despite BCG. The care of BC in the elderly population is of increasing concern and should be addressed in a prospective clinical study.