Search

40 Background: The approval of novel hormonal agents (NHAs), abiraterone and enzalutamide, have increased the therapeutic arsenal available in metastatic castration-resistant prostate cancer (mCRPC). However, the use of chemotherapy and other antineoplastics at the end of life has been suggested as an indicator of poor quality of care. In this study, we report the use of NHAs at the end of life in men with mCRPC in the province of Quebec, Canada. Methods: Using Quebec public healthcare administrative databases, we identified patients with prostate cancer who used an NHA (abiraterone or enzalutamide) after androgen deprivation therapy and who died between 2012 and 2016. The primary outcome was the use of an NHA in the 30 days before death. Use of an NHA in the 60 and 90 days before dying, and initiation (first prescription) of an NHA in the 30 days before death were evaluated as secondary outcomes. Multivariable analysis of the primary outcome was performed with logistic regression with results reported as odds ratios (OR) with 95% confidence intervals (95%CI). Results: The cohort consists of 1316 patients who used an NHA over the course of their disease and died at a median age of 78 years old, with 292 (22.2%), 464 (35.3%), and 575 (43.7%) having used an NHA in the 30, 60 and 90 days of life, respectively. Use of NHA 30 days before dying decreased over the study period, from 44.8% in 2012 to 17.0% in 2016 (Cochran-Armitage test p-value < 0.001). On multivariable analyses, later years of death remained associated with lower odds of NHA use 30 days before death (OR 0.74, 95%CI 0.66 to 0.81, p < 0.001). Fifty-eight (4.4%) patients initiated a NHA 30 days before dying. Conclusions: Rates of NHA use 30 days before dying were high initially but decreased over the study period. Further assessment of NHA use at the end of life is warranted to examine if the trend will be maintained given the recent approval of additional oral NHAs for prostate cancer.

38 Background: Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) treatment, however several side-effects are associated with its long-term use. Notably, loss of bone mineral density (BMD) is accelerated which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to properly assess baseline fracture risk. The objective was to examine the proportion of BMD testing in men initiating long-term ADT in Quebec. Methods: The cohort consists of men extracted from Quebec public healthcare insurance administrative databases who were diagnosed with PCa from 2001-2012 and treated by ADT for at least one continuous year. The primary study outcome was the receipt of baseline BMD testing (defined as a BMD test identified in the period from 6 months prior to and up to 12 months after ADT initiation). Multivariable generalized linear mixed with a logit link was performed to identify variables associated with baseline BMD testing accounting for physician clustering. Results: We identified 7,069 patients, of which 887 (12.6%) underwent baseline BMD testing. Baseline BMD testing varied by year of ADT initiation, from 7.7% in 2001-2003 to 12.3% in 2013-2012. Following multivariable analyses, later years of ADT initiation (2004-2006, 2007-2009, 2010-2012, 2013-2015) remained associated with higher odds of baseline BMD testing compared to the earlier years (2001-2003) (ORs ranging from 1.43-1.88; p < 0.001). Conversely, age > 80 (OR 0.73; 95% CI 0.57-0.94; p = 0.001), greater Charlson comorbidity score (OR 0.51; 95%CI 0.34-0.75; p = 0.001), and rural residence (OR 0.60; 95%CI 0.48-0.75; p < 0.001) were associated with lower odds of baseline BMD testing. Conclusions: In our study population, rates of baseline BMD testing in men initiating ADT are low, although the rates increased over the course of the study period. Potential gaps identified in baseline BMD testing include older, more comorbid patients, and rural residence. Additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

161 Background: Canadian Urological Association guidelines outline the scheduling of imaging modalities based on prostate-specific antigen doubling time (PSADT) to screen for mets in pts with nonmetastatic (M0) CRPC and to manage pts with metastatic (M1) CRPC. Data describing guideline adoption and real-world timing of bone scans and treatment patterns in Canadian CRPC pts are limited. Methods: A retrospective chart review conducted at 13 Canadian urology practices included pts with CRPC (PSA ≥2 ng/mL despite androgen deprivation therapy) sequentially identified in reverse chronological order starting July 30, 2015. Pts had no mets at CRPC diagnosis (index date). Data were abstracted from the index date to the chart review date. Coprimary objectives were to describe CRPC management in terms of timing of the 1st and repeat bone scans in M0 and treatment patterns when pts became metastatic. Secondary objectives described nonbone imaging. Results: 232 pts enrolled. Over the observation period 109 remained nonmetastatic (M0 cohort); 123 developed mets (M1 cohort). Median index PSADT was ~1.5x greater for the M0 cohort than the M1 cohort. 68 pts (71.6%) in M0 and 117 pts (95.1%) in M1 had ≥1 bone scan. Median (95% CI) months from CRPC diagnosis to 1st bone scan was 7.5 (5.6–9.6) for pts in M1 and 15.7 (10.0–23.0) for pts in M0. Median (95% CI) months from identification of mets to start of treatment for the M1 cohort was 3.2 (2.3–5.7). The most common therapies were abiraterone (55%) and enzalutamide (42%), with respective median (95% CI) durations of 12.7 (8.7–23.3) and 15.7 months (10.4–NE). 25% of pts received a bone-targeted agent. Conclusions: In CRPC, time to first bone scan was shorter for pts who subsequently developed mets or had rapid PSADT. Abiraterone and enzalutamide were the most common therapies in pts with mets. [Table: see text]

To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection.We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death.In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival.These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.

Well-characterized, high-quality fresh-frozen prostate tissue is required for prostate cancer research. As part of the PROCURE Prostate Cancer Biobank launched in 2007, four University Hospitals in Quebec joined to bank fresh frozen prostate tissues from radical prostatectomies (RP). As the biobank progressed towards allocation, the nature and quality of the tissues were determined. RP tissues were collected by standardized alternate mirror-image or biopsy-based targeted methods, and frozen for banking. Clinical/pathological parameters were captured. For quality control, two presumed benign and two presumed cancerous frozen, biobanked tissue blocks per case (10/site) were randomly selected during the five years of collection. In a consensus meeting, 4 pathologists blindly evaluated slides (n=160) and graded quality, Gleason score (GS), and size of cancer foci. The quality of tissue RNA (37/40 cases) was assessed using the RNA Integrity Number. The biobank included 1819 patients of mean age: 62.1 years; serum PSA: 8ng/ml; prostate weight: 47.8 g; GS: 7; and pathological stage: T2 in 64.5%, T3A in 25.5% and T3B in 10% of cases. Of the 157 evaluable slides, 79 and 78 had benign and cancer tissue, respectively. GS for the 37 cancer-positive cases were: 6 in 9, 7 in 18 and >7 in 10 and, in most instances, in concordance with final GS. In 40% of slides containing cancer, foci occupied ≥50% of block surface and 42% had a diameter ≥1 cm. Tissue was well preserved and consistently yielded RNA of very good quality with RNA Integrity Number (RIN) >7 for 97% of cases (mean=8.7±0.7) during the five-year collection period. This study confirms the high quality of randomly selected benign and cancerous fresh-frozen prostate tissues of the PROCURE Quebec Prostate Cancer Biobank. These results strengthen the uniqueness of this large prospective resource for prostate cancer research.

We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.

We present the case of a 50-year-old man with a periurethral mass. He was previously known for sclerosing epithelioid fibrosarcoma (SEF) of the left foot, having an amputation for local recurrence with >2 cm negative margins. A solid periurethral mass was surgically excised seven months later, yielding the diagnosis of metastatic SEF. This is the first documented metastasis of SEF to the penis. These sarcomas have proven difficult to treat, with high recurrence rates despite a multimodal approach.

Introduction and objectives Management of bladder cancer imposes a great economic challenge on the health care system; with the greatest share of this burden attributed to radical cystectomy (RC) and prolonged postoperative follow-up. Our aim was to characterize health care services utilization and evaluate associated cost predictors during the last 6 months of life in patients who had RC. Methods We conducted a retrospective study within a cohort of 2,988 patients who had RC from 2000 to 2009. Data were obtained from the Quebec health insurance medical services database. We included patients who deceased during the study period, and survived at least 6 months after the first 90 postoperative days. Services billing codes were used to retrieve hospital, outpatient and imaging services. Linear regression models were used to assess predictors of costs. Results From the 1,355 patients who deceased during the study period, we analyzed data of 799 subjects. Men formed 77.3% and 52.8% of patients were between 60 and 75 years of age at the time of RC. In their last 6 months of life, 17.2% of patients had surgery for major urinary tract complications, 25% had chemotherapy whereas 27.6% had radiotherapy. Also, 3.5% of patients had hemodialysis. Imaging was performed in 94.6% of patients. Urologist (specialist) visits ranked first where 72.3% of patients had 3,481 visits (average = 6 visits/pt) followed by medical subspecialist where 69% of patients had 10,010 visits (average = 18 visits/pt). For supportive care, 97% of patients had 25,560 family physician visits (average = 31 visits/pt) whereas only 16% of them had highly specialized care. Services utilization kept increasing with time especially during the last 2 months before death. Post-RC complications were significant predictor associated with increased costs at all assessed services ( P Conclusion Our study results suggest that health care services utilization varies in the assessed period. Urologists involvement in the process of care tends to decrease over time, in favor of other medical specialties, however, some health care services, such as highly specialized supportive care, may be underutilized.

Purpose Recent observational studies have associated the use of androgen deprivation therapy (ADT) with an increased risk of dementia and Alzheimer’s disease, but these studies had limitations. The objective of this study was to determine whether the use of ADT is associated with an increased risk of dementia, including Alzheimer’s disease, in patients with prostate cancer. Patients and Methods Using the United Kingdom’s Clinical Practice Research Datalink, we assembled a cohort of 30,903 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1988 and April 30, 2015, and observed them until April 30, 2016. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% CIs of dementia associated with the use of ADT compared with nonuse. ADT exposure was lagged by 1 year to account for delays associated with the diagnosis of dementia and to minimize reverse causality. Secondary analyses assessed whether the risk varied with cumulative duration of use and by ADT type. Results During a mean (standard deviation) follow-up of 4.3 (3.6) years, 799 patients were newly diagnosed with dementia (incidence, 6.0; 95% CI, 5.6 to 6.4) per 1,000 person-years. Compared with nonuse, ADT use was not associated with an increased risk of dementia (incidence, 7.4 v 4.4 per 1,000 person-years, respectively; adjusted hazard ratio, 1.02; 95% CI, 0.87 to 1.19). In secondary analyses, cumulative duration of use ( P for heterogeneity = .78) and no single type of ADT were associated with an increased risk of dementia. Conclusion In this population-based study, the use of ADT was not associated with an increased risk of dementia. Additional studies in different settings are needed to confirm these findings.

Biobanking biological samples involve multiple handling, processing, and labeling steps. Each step may be a source of error, which if unnoticed or uncorrected may have consequences for research. We aimed to develop a simple and inexpensive genotyping method that would be valuable to detect such errors and confirm sample identity. For this purpose, seven variable number of tandem repeat (VNTR) loci were selected, analyzed by polymerase chain reaction (PCR) amplification, and organized in a PCR-based DNA profiling algorithm that proved useful to minimize the number of steps required for the procedure. Match probability calculations suggest that this method/algorithm has the potential to discriminate every participant of a biobank. As a proof of concept, the algorithm was applied on samples taken from the PROCURE Prostate Cancer Biobank. It was applied on 403 DNA samples from 101 randomly chosen patients who provided prostate tissues at surgery and blood at two to three different time points over a period of up to 7 years. A unique DNA profile requiring the analysis of no more than four VNTR loci (D16S83, D17S5, D1S80, D19S20) was successfully obtained for each of the 101 cases studied and led to the identification of two mismatches among the 403 samples evaluated (0.5% error rate). Further investigations using the same genotyping method revealed that one of the errors was due to tissue mishandling and that the other was due to tissue mislabeling. These errors, typical to the complex biobanking process, highlight the importance to implement a routine genotyping method as part of quality assurance in biobanking.

Background Survival in patients with bladder cancer has only moderately improved over the past 2 decades. A potential reason for this is nonadherence to clinical guidelines and best practice, leading to wide variations in care. Common quality indicators (QIs) are needed to quantify adherence to best practice and provide data for benchmarking and quality improvement. Objective To produce an evidence- and consensus-based list of QIs for the management of bladder cancer. Methods A modified Delphi method was used to develop the indicator list. Candidate indicators were extracted from the literature and rated by a 27-member Canadian expert panel in several rounds until consensus was reached on the final list of indicators. In rounds with numeric ratings, a frequency analysis was performed. Results A total of 86 indicators were rated, 52 extracted from the literature and 34 suggested by the panel. After iterative rounds of ratings and discussion, a final list of 60 QIs spanning several disciplines and phases of the cancer care continuum was developed. Conclusions This is the first study to comprehensively produce common QIs representing structure, process, and outcome measures in bladder cancer management. Though developed in Canada, these indicators can be used in other countries with slight modifications to track performance and improve care.

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer death, and distinguishing aggressive from indolent tumors is a major challenge. Identification and characterization of genomic alterations associated with advanced disease can provide new markers of progression and better therapeutic approaches. METHODS: We performed fluorescence in situ hybridization to detect the copy number gain of chromosome 16p13.3 in 75 PCa samples including 10 lymph node (LN) metastases and their matched primary tumors, 9 samples of castration-resistant prostate cancer (CRPC), and 46 additional primary PCa specimens with clinicopathologic parameters. RESULTS: We detected the gain in 5 of 10 LN metastases and 3 of 5 matched primary tumors, 3 of 9 CRPC samples, and 9 of 46 (20%) primary tumors where the 16p13.3 alteration was associated with high Gleason score and elevated preoperative prostate-specific antigen levels. The level of 16p13.3 gain was higher in LN metastasis and CRPC specimens compared to primary PCa. Chromosome mapping revealed the gain spans PDPK1 encoding the 3-phosphoinositide-dependent protein kinase-1 (PDK1). Knockdown of PDK1 in three PCa cell lines reduced migration without affecting growth and re-expressing PDK1 rescued motility. CONCLUSION: Our findings support a prognostic value of the 16p13.3 gain and a role of PDK1 in PCa progression through migration.

Study Type – Therapy (retrospective cohort) Level of Evidence 3a What's known on the subject? and What does the study add? It is known that the majority (80%) of solid renal masses are malignant. Most of the literature suggests that smaller tumour size is associated with a higher incidence of benign disease. We have confirmed that decreased tumour size is associated with benign disease, particularly for lesions

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease. OBJECTIVES • To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC). • To establish appropriate surveillance protocols. PATIENTS AND METHODS • We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres. • Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study. RESULTS • A total of 825 patients (43.6%) developed recurrence. • According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant. • The median (range) time to recurrence for the entire population was 10.1 (1–192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively. • According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5-yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1–72 months) than ≥pT3N0 tumours (10 months, range 1–70 months) or ≤pT2N0 tumours (14 months, range 1–192 months, P < 0.001). CONCLUSIONS • Differences in recurrence patterns after RC suggest the need for varied follow-up protocols for each group. • We propose a stage-based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over-investigation.

Background The psychosocial dimension of prostate cancer has received increased attention over the past 2 decades. Objectives The objectives of the study were to investigate the men's psychosocial adjustment over the course of the first year of prostate cancer and to examine the sense of coherence, couple cohesion and adaptability, sexual and urinary symptoms, and mood disturbance as predictors of their adjustment. Methods There were 81, 69, and 61 men visited at home prior to treatment (T1), 3 months later (T2), and 1 year after the first visit (T3), respectively. Repeated-measures analyses of variance were used to examine adjustment over time. Multiple regressions determined whether the predictors were associated with the adjustment domains. Results Sexual relationship deteriorated and social environment improved between T1 and T2. Between T1 and T3, sexual, domestic, and family relationships deteriorated, whereas social environment improved. Mood disturbance, sense of coherence, couple cohesion, and couple adaptability were predictors of psychological, vocational, and domestic domains at T1. At T2, mood disturbance and sexual functioning were predictors of healthcare, vocational, social, psychological, and family domains. At T3, couple cohesion and adaptability and urinary functioning were predictors to vocational, domestic, social, and psychological adjustment. Conclusions During the first year of prostate cancer, men showed deterioration in sexual, close-family, and extended-family relationship domains. Implications for practice Sexuality is an important topic, and spousal communication should be encouraged throughout the first year following diagnosis. Preparedness for the changes associated with prostate cancer along with continuing support to couples, rather than to patients only, might be the strongest approach to enhancing men's adjustment.

To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma.Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N = 365) and (Group 2) patients with clinical muscle invasive cancer de novo (N = 785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality.Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7 years, and 79.7 and 79.5%, respectively (P = 0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P = 0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P0.0001), positive lymph nodes were 20.1 and 28.8% (P = 0.002), and lymphovascular invasion was 31.7 and 46.2% (P = 0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P = 0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5 years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10 years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P = 0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P = 0.0002).Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo.

Objective To assess outcome in patients with T1 high-grade (T1HG) bladder cancer treated at a single academic institution and to determine the prognostic factors that can help in counselling patients towards early cystectomy. Patients and methods Records of 2570 patients with bladder cancer treated from 1995 to 2005 were reviewed. Only patients diagnosed with T1HG disease were included in the analysis. Collected variables included various clinicopathological parameters, use of statins, smoking, as well as dates of recurrence, progression, radical cystectomy and death. Recurrence-free survival (RFS) and worsening-free survival (WFS) were analyzed. Multivariate Cox proportional regression analysis was employed to verify the prognostic significance of various variables. Results In total, 278 (10.8%) patients were identified as having T1HG disease on transurethral resection. 66% of patients who recurred, and 36.3% developed stage progression after a median (range) follow-up of 3 (0.1-15.4) years. 30% patients who underwent radical cystectomy, and 9% were dead of disease. The 5-year RFS and WFS rates were 26.6% and 49.4%, respectively. On multivariate analysis, only non-trigonal tumour location, restaging transurethral resection, history of previous carcinoma not invading bladder muscle and adjuvant bacille Calmette-Guerin (BCG) therapy were significantly associated with prolonged RFS, whereas papillary tumour architecture, history of previous carcinoma not invading bladder muscle and adjuvant BCG therapy were significantly associated with prolonged WFS. Conclusions Patients with T1HG bladder cancer are at a significant risk of progression and death from disease. Primary tumours, sessile architecture and trigonal location are factors associated with a worse outcome and may be used to counsel patients towards early cystectomy.

Objectives Aborted cystectomy due to unresectable disease is not uncommon in patients with bladder cancer. Our aim was to review the outcome of these patients and evaluate various prognostic variables. Materials and methods Thirty-one bladder cancer patients who underwent aborted radical cystectomy due to unresectable disease from 1993 to 2007, and form the basis of this report. Survival was estimated by the Kaplan and Meier method, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. Results Mean age of patients was 66 years with median follow-up of patients alive 10 months. The 2- and 5-year overall survival (OS) was 41% and 0%, respectively. Twenty patients had a pelvic lymph node dissection (PLND) and 11 patients did not. Twenty-three patients received postoperative therapy, of whom 8 received chemotherapy with the intent of surgical consolidation (only 2 were rendered resectable thereafter), and 15 received combined chemoradiation. OS was not significantly associated with hydronephrosis, concomitant CIS, performance status, history of superficial tumors, postoperative therapy, and salvage cystectomy. Patients with pN2-3 had similar overall survival compared with those with pT4b (13 vs. 17 months, P = 0.59). However, patients who underwent PLND trended towards improved OS compared with those who did not (24 vs. 10 months, P = 0.09). Conclusions Outcome of patients with unresectable disease is dismal. Patients who had an aborted cystectomy due to unresectable disease may benefit from PLND. Further refinements of clinical staging to better identify these patients preoperatively and offer them upfront chemotherapy are needed.

Background: Hematuria is one of the most common findings on urinalysis in patients encountered by primary care physicians. In many instances it can also be the first presentation of a serious urological problem. As such, we sought to evaluate current practices adopted by primary care physicians in the workup and screening of hematuria. Methods: Questionnaires were mailed to all registered primary care physicians across Quebec. Questions covered each physician’s personal approach to men and postmenopausal women with painless gross hematuria or with asymptomatic microscopic hematuria, as well as screening techniques, general knowledge with regards to urine collection and sampling, and referral patterns. Results: Of the surveys mailed, 599 were returned. Annual routine screening urinalysis on all adult male and female patients was performed by 47% of respondents, regardless of age or risk factors. Of all the respondents, 95% stated microscopic hematuria was associated with bladder cancer. However, in an older male with painless gross hematuria, only 64% of respondents recommended further evaluation by urology. On the other hand, in a postmenopausal woman with 2 consecutive events of significant microscopic hematuria, only 48.6% recommended referral to urology. Findings were not associated with the gender of the respondent, experience or geographic location of practice (urban vs. rural). Interpretation: There seems to be reluctance amongst primary care physicians to refer patients with gross or significant microscopic hematuria to urology for further investigation. A higher level of suspicion and further education should be implemented to detect serious conditions and to offer earlier intervention when possible.

Study Type – Therapy (practice pattern survey) Level of Evidence 2b What’s known on the subject? and What does the study add? Benign prostatic hyperplasia is one of the most common urologic conditions encountered by general practitioners. 5-alpha-reductase inhibitors are newer drugs used for its treatment. Their use, however, can affect PSA kinetics and potentially mask the early detection of prostate cancer. This study further confirms that most general practitioners prefer to use alpha-blockers over 5-alpha-reductase inhibitors in the management of BPH. Furthermore, it clearly shows that there is a lack of awareness of the effect of these medications on PSA kinetics and, as such, further education among GPs is recommended about these drugs in order to optimize their usage at the primary care level and to avoid delays in cancer detection. OBJECTIVE • To investigate among general practitioners (GPs) their level of awareness and indications for urological consultations in patients treated with 5α-reductase inhibitors (5ARIs). SUBJECTS AND METHODS • We conducted a survey of GPs in Quebec. • Questions covered GPs’ preferred benign prostatic hyperplasia (BPH) management, knowledge of 5ARIs, their role in prostate cancer prevention, and triggers for urology consultation. RESULTS • Of the surveys mailed, 599 were returned (15.7% response rate). • Therapy with 5ARIs was initiated by GPs in 34.3%, with 20% and 12% preferring 5ARIs alone and combined with an α-blocker as first-line therapy for BPH, respectively. • Once on therapy, 74% did not refer to a urologist if the PSA level did not decline after 6–12 months. • Finally, 40.7% would not advocate 5ARI chemoprevention for prostate cancer, regardless of risk reduction. • Findings were not associated with GP gender, experience or geographic location of practice (urban versus rural). CONCLUSIONS • There was a preference amongst GP to use α-blockers over 5ARIs for BPH and hesitancy to use them in prostate cancer chemoprevention. • There is a lack of awareness of 5ARI effects on PSA kinetics and a reluctance to refer to a urologist. • Further education in Quebec is needed about 5ARIs to optimize their usage and avoid delaying cancer detection.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate data obtained from a large, multi-institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables. MATERIALS AND METHODS Data were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS The median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrence-free and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was

The objective of our study is to examine the correlation between PSA density (PSAd) at the time of diagnosis with PSA velocity (PSAV), PSA doubling time and tumour progression, on repeat biopsy, in men with prostate cancer on active surveillance. Data from 102 patients with clinically localized prostate cancer on active surveillance in the period between 1992 and 2007, who had the necessary parameters available, were collected. PSAd was calculated and correlated with PSAV, PSA doubling time (PSADT), Gleason score at diagnosis and local progression on repeated biopsies. PSAV was 0.64 and 1.31 ng ml(-1) per year (P = 0.02), PSADT of 192 and 113 months (P = 0.4) for PSAd below and above 0.15, respectively. The rate of detecting high Gleason score (≥ 7) at diagnosis was 6 and 23% for PSAd below and above 0.15, respectively. A total of 101 patients underwent at least a second biopsy and the incidence of upgrading was 10 and 31% for PSAd below and above 0.15, respectively (P = 0.001). Although low PSAd is an accepted measure for suggesting insignificant prostate cancer, our study expands its role to indicate that PSAd0.15 may be an additional clinical parameter that may suggest indolent disease, as measured by future PSAV and repeat biopsy over time.

Objectives To evaluate performance and cost-effectiveness of voided cytology in patients with pure asymptomatic microscopic hematuria (AMH). Although voided cytology has been validated for use in patients with a history of urothelial carcinoma (UC), its use in low-risk patients with AMH is controversial. Methods A total of 200 consecutive low-risk patients (median age, 64 years) with AMH were referred to the urology clinic between 2005 and 2007. All underwent cystoscopy, upper tract imaging, and voided urinary cytology. Results of voided cytology were classified as positive, atypical, or negative. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and costs were calculated. Results None had positive cytology, 23 (11.5%) had atypical cytology, and 177 (88.5%) had negative urinary cytology. Of 200 patients, 8 (4%) were found to have low-grade UC of bladder via cystoscopy; the cytology was negative in 4 patients and atypical in 4. Of 8, 4 were Ta and 4 were pT1 tumors. There was no upper urinary tract or renal malignancy identified. If atypical cytology was considered as positive, the sensitivity, specificity, PPV, and NPV of cytology were 50%, 90%, 17%, and 98%, respectively. If atypical cytology was considered as negative, the sensitivity, specificity, PPV, and NPV of cytology were 0%, 100%, 0%, and 96%, respectively. Cost of performing urinary cytology was estimated at $262.50 per patient. Conclusions Although this study supports evaluating patients with AMH because a significant percentage of patients will have UC, voided urine cytology added a significant cost without any diagnostic benefit in the work-up of low-risk patients with AMH.

80 Background: The CPCBN has assembled a TMA-based resource comprising the specimens of 1512 prostate cancer patients treated by radical prostatectomy. This richly annotated and multi-institutional resource is available to researchers who wish to access a large cohort to validate prognostic biomarkers (http://www.tfri.ca/en/research/translational-research/cpcbn.aspx). Over the last decade, our laboratory demonstrated with an independent cohort (Gannon PO, et al. Eur J Cancer. 2013 Jul;49(10):2441-8, Labouba I, et al. PLoS One. 2015 Jul 17;10(7):e0131024), the reproducible association of nuclear factor-kappa B (NF-kB) p65 with patient’s risk of biochemical recurrence. Here, we evaluated the CPCBN TMA-series for p65 expression. Methods: Two independent observers scored the frequency of p65 nuclear localisation on digital images obtained after automated immunohistochemistry analysis of p65. Over the available minimum 3 cores of tumour tissue per patient, an average percentage of positive nucleus frequency was used. Statistical analyses were performed using SPSS software. Results: High nuclear frequency of NF-kB p65 (cut-off at 3%) was associated with an increased risk for patients to experience a biochemical relapse (p < 0.001; Exp(B) = 1.599; 95%CI = 1.321-1.937), develop bone metastasis (p = 0.007; Exp(B) = 2.126; 95%CI = 1.234-3.663)and die from their disease (p = 0.001; Exp(B) = 3.117; 95%CI = 1.55-6.266). In multivariate analyses, p65 also remained independent from clinical parameters (PSA, Gleason score and pTNM): biochemical relapse (p = 0.005; Exp(B) = 1.331; 95%CI = 1.092-1.623), bone metastasis (p = 0.033; Exp(B) = 1.82; 95%CI = 1.04- 3.158), mortality (p = 0.007; Exp(B) = 2.626; 95%CI = 1.298-5.312) Conclusions: Using a large cohort of Canadian men, our study reiterates the previous study linking NF-kB p65 with prostate cancer progression and highlights the suitability of CPCBN TMAs for biomarker validation. Our results also reveal the role of p65 as a predictor of bone metastasis development and prostate cancer-specific mortality.

Partial cystectomy (PC) remains a viable alternative to radical cystectomy (RC) for management of invasive bladder cancer in approximately 5% of patients. We used a population-based database to examine practice patterns and recurrence after partial cystectomy. We obtained billing records of all partial and radical cystectomies performed for bladder cancer in Quebec from 1983 until 2005. Analysis included age, gender, year of surgery, surgeon’s age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of recurrences salvage RC, and death. A total of 714 (30.4%) patients with invasive bladder cancer underwent PC. Majority of PC (65%) were performed in non-academic institutions. Pelvic lymphadenectomy was performed in only 163 patients (23%) and concomitant ureteral reimplantation was performed in 89 patients (13%). Of 714 patients, 52 (23.7%) required a salvage RC. Median time from PC to salvage RC was 17.6 months (range 1–240 months), respectively. Patients who underwent PC had similar 5-year overall survival compared with patients who underwent upfront RC (49.8% vs. 51%, p = 0.21). Rate of PC for invasive bladder cancer is significantly higher than expected. Pelvic lymphadenectomy is underutilized in bladder cancer patients treated with PC. Whether prevalent use of PC is due to less stringent selection criteria remains unknown. Since late recurrence is not uncommon, lifelong follow-up is recommended.

Urinary retention is common after anesthesia and surgery, reported incidence of between 5% and 70%. Comorbidities, type of surgery, and type of anesthesia influence the development of postoperative urinary retention (POUR). The authors review the overall incidence and mechanisms of POUR associated with surgery, anesthesia and analgesia. Ultrasound has been shown to provide an accurate assessment of urinary bladder volume and a guide to the management of POUR. Recommendations for urinary catheterization in the perioperative setting vary widely, influenced by many factors, including surgical factors, type of anesthesia, comorbidities, local policies, and personal preferences. Inappropriate management of POUR may be responsible for bladder overdistension, urinary tract infection, and catheter-related complications. An evidence-based approach to prevention and management of POUR during the perioperative period is proposed.

Androgen withdrawal is the most effective form of systemic therapy for men with advanced prostate cancer. Unfortunately, androgen-independent progression is inevitable, and the development of hormone-refractory disease and death occurs within 2 to 3 years in most men. The understanding of molecular mechanisms promoting the growth of androgen-independent prostate cancer cells is essential for the rational design of agents to treat advanced disease. We previously reported that Fer tyrosine kinase level correlates with the development of prostate cancer and aggressiveness of prostate cancer cell lines. Moreover, knocking down Fer expression interferes with prostate cancer cell growth in vitro. However, the mechanism by which Fer mediates prostate cancer progression remains elusive. We present here that Fer and phospho-Y705 signal transducer and activator of transcription 3 (STAT3) are barely detectable in human benign prostate tissues but constitutively expressed in the cytoplasm and nucleus of the same subsets of tumor cells in human prostate cancer. The interaction between STAT3 and Fer was observed in all prostate cancer cell lines tested, and this interaction is mediated via the Fer Src homology 2 domain and modulated by interleukin-6 (IL-6). Moreover, IL-6 triggered a rapid formation of Fer/gp130 and Fer/STAT3 complexes in a time-dependent manner and consistent with changes in Fer and STAT3 phosphorylation and cytoplasmic/nuclear distribution. The modulation of Fer expression/activation resulted in inhibitory or stimulatory effects on STAT3 phosphorylation, nuclear translocation, and transcriptional activation. These effects translated in IL-6–mediated PC-3 cell growth. Taken together, these results support an important function of Fer in prostate cancer. (Mol Cancer Res 2009;7(1):142–55)

Chemoprevention is the use of natural or synthetic agents that reverse, inhibit or prevent the development of cancer with the least possible adverse effects in cancer-free individuals. Prostate cancer has the highest incidence and the second highest cancer mortality in American men. Risk factors include age, ethnicity, family history, genetics, inflammation and obesity. Based on level 1 evidence, finasteride (a 5α-reductase inhibitor) is the only agent that has been demonstrated to decrease the risk of developing prostate cancer. Further studies are needed to evaluate whether other potential agents (including lycopene, vitamin E, selenium, anti-inflammatory agents, selective estrogen-receptor modulators, statins, soy, green tea, pomegranate, red wine and curcumin) have a role in the chemoprevention of prostate cancer. The hurdles are finding the agents that offer a reduction in risk at a low cost while having minimal side effects in an otherwise healthy population.

BACKGROUND. Active surveillance (AS) with deferred treatment is an established management option for patients with prostate cancer and favorable clinical parameters. The impact of repeat biopsy after diagnosis was examined in a cohort of men with prostate cancer on AS. METHODS. In all, 186 men with prostate cancer with favorable parameters or who refused treatment were conservatively managed by AS. Of these, 92 patients had at least 1 biopsy after diagnosis. Patients were followed every 3 to 6 months with prostate-specific antigen (PSA) and physical examination and were offered rebiopsy annually or if there were any changes on physical examination or in the PSA value. Disease progression while on AS was defined as having ≥1 of the following: ≥cT2b disease, ≥3 positive cores, >50% of cancer in at least 1 core, or a predominant Gleason pattern of 4 in rebiopsies. RESULTS. The median age of the patients at the time of diagnosis was 67 years (range, 49–78 years). The median follow-up was 76 months (range, 20–169 months). Of the 92 patients who underwent repeat biopsies, 42 patients, 25 patients, 13 patients, 10 patients, and 2 patients had 1, 2, 3, 4, and 5 rebiopsies, respectively. A total of 34 patients (36%) demonstrated disease progression on rebiopsy. The first rebiopsy was positive for cancer in 48 patients (52.2%) and negative in 44 patients (47.8%). The 5-year actuarial progression-free probability was 82% for patients with a negative first repeat biopsy compared with 50% for patients with a positive first rebiopsy (P = .02). A PSA doubling time

Purpose: Tookad® is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy. Materials and Methods: Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes. Results: Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained. Conclusions: Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.

Purpose: Cluster-of-differentiation antigen 9 (CD9) protein, a member of the tetraspanin family, has been implicated in carcinogenesis of various human tumors. Although decreased expression of the CD82 tetraspanin protein, a close CD9 relative, is associated with prostate cancer progression, CD9 expression has not been analyzed in this malignancy. Experimental Design: CD9 expression in human prostatic adenocarcinoma was analyzed by immunohistochemistry on 167 primary tumors and 88 lymph node or bone metastases. CD9 cDNA was sequenced from two human prostate cancer cell lines, prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and normal prostatic tissues. Results: Although CD9 was detected in the epithelium of normal prostatic tissues, reduced or loss of CD9 expression within neoplastic cells was observed in 24% of 107 clinically localized primary adenocarcinomas, 85% of 60 clinically advanced primary adenocarcinomas, 85% of 65 lymph node metastases, and 65% of 23 bone metastases. Difference in CD9 expression between clinically localized and advanced diseases was highly significant (P < 1 × 10−7). Whereas there was no alteration of CD9 cDNA in normal tissues, all PC-3–derived cell lines, one PIN, and four prostatic adenocarcinomas harbored deletions in their CD9 cDNAs. Recurring CD9 point mutations were also found in PC-3M-LN4 cells, one PIN, and seven prostatic adenocarcinomas. Conclusions: CD9 expression is significantly reduced and even lost during prostate cancer progression. Moreover, deletions and mutations of the CD9 mRNA may be associated with loss of protein expression observed in tumor cells. Our data suggest that CD9 inactivation may play an important role in prostate cancer progression.

Background Clinical applicability of newly discovered reagents for molecular imaging is hampered by the lack of translational models. As the dog prostate cancer (DPC-1) model recapitulates in dogs the natural history of prostate cancer in man, we tested the feasibility of single-photon emission computed tomography (SPECT)/CT imaging in this model using an anti-prostate-specific membrane antigen (PSMA)/17G1 antibody as the radiotracer. Methods Immunoblots and immunohistochemistry (IHC) with 17G1 were performed on canine and human prostate cancer cell lines and tissues. Five dogs with DPC-1 tumors were enrolled for pelvic and, in some instances, thoracic SPECT/CT procedures, also repeated over time. Controls included 111indium (In)-17G1 prior to DPC-1 implantation and 111In-immunoglobulins (IgGs) prior to imaging with 111In-17G1 in dogs bearing prostatic DPC-1 tumors. Results 17G1 cross-reactivity with canine PSMA (and J591) was confirmed by protein analyses on DPC-1, LNCaP, and PC-3 cell lines and IHC of dog vs. human prostate tissue sections. 17G1 stained luminal cells and DPC-1 cancer cells in dog prostates similarly to human luminal and cancer cells of patients and LNCaP xenografts. SPECT/CT imaging revealed low uptake (≤2.1) of both 111In-17G1 in normal dog prostates and 111In-IgGs in growing DPC-1 prostate tumors comparatively to 111In-17G1 uptake of 3.6 increasing up to 6.5 values in prostate with DPC-1 lesions. Images showed a diffused pattern and, occasionally, a peripheral doughnut-shape-like pattern. Numerous sacro-iliac lymph nodes and lung lesions were detected with contrast ratios of 5.2 and 3.0, respectively. The highest values were observed in pelvic bones (11 and 19) of two dogs, next confirmed as PSMA-positive metastases. Conclusions This proof-of-concept PSMA-based SPECT/CT molecular imaging detecting primary prostate tumors and metastases in canines with high cancer burden speaks in favor of this large model’s utility to facilitate technology transfer to the clinic and accelerate applications of new tools and modalities for tumor staging in patients. Electronic supplementary material The online version of this article (doi:10.1186/s13550-015-0155-6) contains supplementary material, which is available to authorized users.

Background RNA-binding motif protein 3 (RBM3), involved in cell survival, has paradoxically been linked to both oncogenesis as well as an increased survival in several cancers, including urothelial carcinoma (UCA). Methods The putative prognostic role of RBM3 was studied using cystectomy specimens with 152 invasive UCA with 35 matched metastases, 65 carcinomas in situ (CIS), 22 high-grade papillary UCAs (PAP), and 112 benign urothelium cases. Results The H-score (HS, staining intensity × % of positive cells) was used for RBM3 immunoexpression. CIS showed the highest HS (mean = 140) followed by benign urothelium (mean = 97). Metastases showed higher HS than primary invasive UCA (P ≤ 0.0001), and high HS was associated with a lower pT stage (P ≤ 0.0001) and a trend toward the absence of lymphovascular invasion (LVI, P = 0.09), but not pN stage (P = 0.35) and surgical margin status (P = 0.81). Univariate analysis (UVA) of disease recurrence only showed an association between pN stage and LVI (P = 0.005 and 0.03, respectively). On UVA of mortality, pT stage was strongly associated with death (P = 0.01) while pN stage, LVI, surgical margin status, and HS were not. Multivariate analysis confirmed the lack of HS association with recurrence (P = 0.08) and death (P = 0.32). Conclusions Stronger RBM3 immunoexpression correlated with lower stage tumors and a diminished risk for LVI. However, RBM3 does not seem to carry a prognostic significance for clinical outcome (recurrence and mortality). The exact prognostic role of RBM3 in UCA is yet to be determined.

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects., National Institutes of Health (U.S.). (grant 5U24CA143799), National Institutes of Health (U.S.). (grant 5U24CA143835), National Institutes of Health (U.S.). (grant 5U24CA143840), National Institutes of Health (U.S.). (grant 5U24CA143843), National Institutes of Health (U.S.). (grant 5U24CA143845), National Institutes of Health (U.S.). (grant 5U24CA143848), National Institutes of Health (U.S.). (grant 5U24CA143858), National Institutes of Health (U.S.). (grant 5U24CA143866), National Institutes of Health (U.S.). (grant 5U24CA143867), National Institutes of Health (U.S.). (grant 5U24CA143882), National Institutes of Health (U.S.). (grant 5U24CA143883), National Institutes of Health (U.S.). (grant 5U24CA144025), National Institutes of Health (U.S.). (grant U54HG003067), National Institutes of Health (U.S.). (grant U54HG003079), National Institutes of Health (U.S.). (grant U54HG003273), National Institutes of Health (U.S.). (grant P30CA16672)

Urinary cytology (C) and cystoscopy remain the gold standard for the detection and screening of bladder cancer (BC). In this prospective study, we analyzed whether baseline C, ImmunoCyt (I), BTA Stat (B), hemoglobin dipstick (H), and NMP22 BladderChek (N) can predict recurrence and progression. Urinary samples from 91 patients with BC were prospectively collected over an 18-month period. Baseline characteristics of the population included patient demographics, various clinicopathological variables and use of intravesical therapy. Progression and recurrence were then assessed after a median follow-up of 48 months (IQR 23.7–59.5). Univariate and multivariate analyses were performed using COX proportional hazards models. On univariate analysis, C (HR 1.36; p = 0.26), I (HR 0.89; p = 0.66), B (HR 0.80; p = 0.42), H (HR 0.75; p = 0.30), and N (HR 0.82; p = 0.48) were not associated with recurrence-free survival (RFS). With regard to progression-free survival (PFS), C was significantly prognostic (HR 2.67; p = 0.017), whereas I, B, H, and N were not. On multivariable analysis, NMP22 was the only marker to be independently associated with RFS (HR 0.41, p

Background The role of metabolic syndrome (MetS) in prostate cancer risk is still debated. We investigated it in a large population-based case–control study. Methods Cases were 1937 men with incident prostate cancer, aged ≤75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1995 population controls from the same residential area and age distribution were randomly selected from electoral list of French-speaking men. Detailed lifestyle and medical histories, and anthropometric measures, were collected during in-person interviews. Prevalence of MetS components (type 2 diabetes, high blood pressure, dyslipidemia and abdominal obesity) was estimated at 2 years before diagnosis for cases/ interview for controls, and at ages 20, 40, 50 and 60. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals for the association between MetS and prostate cancer risk. Results A history of MetS (≥3 components vs

There is paucity of studies on the predictors of bladder cancer (BC) management costs. We aimed to determine predictors of costs associated with radical cystectomy (RC) for BC.We conducted a retrospective analysis in a cohort of 2,759 patients who underwent RC for BC between 2000 and 2009. We analyzed predictors of pre-surgery, RC, post-surgery, and total costs. The following variables were considered as potential predictors: age, gender, hospital/surgeon case load, academic hospital, and geo-administrative region. Multivariate linear regression was used to determine predictors.Predictors of pre-surgery costs were: age (β = 808.64, P 0.0001) and having surgery in an academic hospital (β = 511.42, P = 0.003). Increased RC costs were associated with age (β = 196.73, P = 0.0006), hospital/surgeon annual load (β = 484.45 and β = 254.21, P 0.0001, respectively). Having surgery in academic hospitals and geographic region were significant predictors of low RC costs (β = -1085.82 and β = -449.31, P 0.0001, respectively). Increasing age and the presence of post-operative complications were predictors of high post-operative costs (β = 623.48, β = 5781.44, P = 0.01, respectively), while hospital load was associated with low post-surgery costs (β = -949.79, P 0.0001).Patients' age and surgery performed by high-volume health providers were predictive factors of high RC costs. Low RC costs were associated with surgeries performed in academic hospitals.

Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer. By lowering androgen levels, ADT inhibits the progression of prostate cancer, but it may also affect gut autoimmunity. We investigated the association between ADT and the incidence of inflammatory bowel disease using a cohort of 31,842 men newly diagnosed with prostate cancer between 1988 and 2014, identified in the United Kingdom Clinical Practice Research Datalink. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays, with nonuse as the reference category. During 133,018 person-years of follow-up, 48 men were newly diagnosed with ulcerative colitis (incidence rate (IR) = 36/100,000 person-years (PY)) and 12 were diagnosed with Crohn's disease (IR = 9/100,000 PY). In Cox proportional hazards models, ADT was associated with a decreased risk of ulcerative colitis (IR = 24/100,000 PY vs. IR = 50/100,000 PY; hazard ratio = 0.52, 95% confidence interval: 0.28, 0.99) and a nonsignificant decreased risk of Crohn's disease (hazard ratio = 0.38, 95% confidence interval: 0.11, 1.37). These findings indicate that the use of ADT may be associated with intestinal autoimmunity. Further research is warranted to replicate these findings and assess their clinical significance.

Introduction Transrectal ultrasound-guided biopsy (TRUSGB) is the recommended approach to diagnose prostate cancer (PCa). Overdiagnosis and sampling errors represent major limitations. Magnetic resonance imaging (MRI)-targeted biopsy (MRTB) detects higher proportion of significant PCa and reduces diagnosis of insignificant PCa. Costs prevent MRTB from becoming the new standard in PCa diagnosis. The present study aimed at assessing whether added costs of MRI outweigh benefits of MRTB in a cost-utility model. Materials and methods A Markov model was developed to estimate quality-adjusted life-year gained (QALY) and costs for 2 strategies (the standard 12-core TRUSGB strategy and the MRTB strategy) over 5, 10, 15, and 20 years. MRI was used as triage test in biopsy-naive men with clinical suspicion of PCa. The model takes into account probability of men harboring PCa, diagnostic accuracy of both procedures, and probability of being assigned to various treatment options. Direct medical costs based on health care system perspective were included. Results Following standard TRUSGB pathway, calculated cumulative effects at 5, 10, 15, and 20 years were 4.25, 7.17, 9.03, and 10.09 QALY, respectively. Cumulative effects in MRTB pathway were 4.29, 7.26, 9.17, and 10.26 QALY, correspondingly. Costs related to TRUSGB strategy were $8,027, $11,406, $14,883, and $17,587 at 5, 10, 15, and 20 years, respectively, as compared with $7,231, $10,450, $13,267, and $15,400 for the MRTB strategy. At 5, 10, 15, and 20 years, MRTB was the established dominant strategy. Conclusions Incorporation of MRI and MRTB in PCa diagnosis and management represents a cost-effective measure at 5, 10, 15, and 20 years after initial diagnosis.

Background Few observational studies have investigated the association between androgen deprivation therapy (ADT) and venous thromboembolism (VTE) in patients with prostate cancer (PCa). Objective To determine whether the use of different types of ADT in patients with PCa is associated with an increased incidence of VTE. Design, setting, and participants A population-based cohort study was conducted using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of men newly diagnosed with PCa between April 1, 1998, and March 31, 2014. Outcome measures and statistical analysis Cox proportional hazards models with a time-varying exposure definition were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of patients hospitalized for VTE associated with current and past ADT use compared with nonuse. A secondary analysis was conducted to assess the risk with current use of specific types of ADT. Results and limitations The cohort included 21 729 patients, of whom 609 were hospitalized for VTE during follow-up. Current ADT use was associated with an 84% increased risk of VTE (incidence rates: 10.1 vs 4.8 per 1000 person-years; HR: 1.84; 95% CI, 1.50–2.26), whereas there was no association with past use (HR: 1.07; 95% CI, 0.81–1.42). In the secondary analysis, most types of ADT were associated with a high risk of VTE. Residual confounding is possible given the observational nature of the study. Conclusions The use of ADT was associated with an overall 84% increased risk of VTE, with the risk elevated for most ADT types. Patient summary In this study, we investigated whether androgen deprivation therapy was associated with the risk of blood clots in a cohort of patients with prostate cancer. We observed that the risk was nearly doubled in patients who used ADT compared with those who never used it. This treatment should be reserved for patients for whom the benefits outweigh the risks.