Biospecimen Qualification in a Clinical Biobank of Urological Diseases.

Development of novel biomarkers for diagnosis of disease and assessment of treatment efficacy utilizes a wide range of biospecimens for discovery research. The fitness of biospecimens for the purpose of biomarker development depends on the clinical characteristics of the donor and on a number of critical and potentially uncontrolled pre-analytical variables. Pre-analytical factors influence the reliability of the biomarkers to be analyzed and can seriously impact analytic outcomes. Sample quality stratification assays and tools can be utilized by biorepositories to minimize bias resulting from samples' inconsistent quality. In this study, we evaluated the quality of biobanked specimens by comparing analytical outcomes at 1, 5, and 10 years after collection. Our results demonstrate that currently available assays and tools can be used by biobank laboratories to support objective biospecimen qualification. We have established a workflow to monitor the quality of different types of biospecimens and, in this study, present the results of a qualification exercise applied to fluid samples and their derivatives in the context of urological diseases.

Quantitative and qualitative impact of physician assistants in a Canadian urology setting.

INTRODUCTION: Physician assistants (PAs) are healthcare professionals who act as physician extenders. PAs are being used more and more in a wide variety of clinic settings throughout Canada to increase access to healthcare and reduce cost. We set out to determine the impact of PAs on a tertiary care center urologic oncology practice. METHODS: We reviewed Ontario Health Insurance Plan (OHIP) billing codes since the introduction of PAs for two attending urologists at Princess Margaret Cancer Centre. Data were grouped into early experience and established experience. In addition, questionnaires were electronically distributed among nurses, physicians, residents, and fellows who work with PAs in clinic. Patient visits conducted by PAs were tracked for one quarter to estimate the amount of annual patients seen by PAs. The costs associated with PAs are presented as recommendations for a new graduate PA hire. RESULTS: On average, PAs increased clinic volume by 11.3 patient visits per day. Furthermore, they individually care for an average of 24 patients per day. PAs did not represent a financial burden on the urology practice plan (revenue gain of $16 800). Our questionnaire demonstrated that PAs were capable healthcare professionals, who decreased workload and contributed to resident/fellow education. CONCLUSIONS: PAs in a Canadian urology practice allow for more patient visits, decrease in physician workload, and positively impact trainee education. PAs saw more patients in clinic than clinic growth, thereby decreasing physician, fellow, and resident workload. The offset of the increase in patient visits made the PAs a cost-neutral investment.

Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial.

PURPOSE: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer. PATIENTS AND METHODS: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile. RESULTS: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0-68.0] and 21.9 ng/mL (IQR, 14.6-42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078). CONCLUSIONS: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

Expansion of Lymphocytes from Prostatic Adenocarcinoma and Adjacent Nonmalignant Tissue.

Background: The evaluation of tumour-infiltrating lymphocytes (TILs) in solid malignancies has yielded insights into immune regulation within the tumour microenvironment and has also led to the development and optimisation of adoptive T cell therapies. Objectives: This study examined the in vitro expansion of TILs from prostate adenocarcinoma, as a preliminary step to evaluate the potential of TILs for adoptive T cell therapy. Design, Setting, and Participants. Malignant and adjacent nonmalignant tissues were obtained from fifteen men undergoing radical prostatectomy. Interventions. There were no study interventions. Outcome Measurements and Statistical Analysis. Expanded cells were analysed by flow cytometry, and the data was assessed for associations between cell subpopulations and expansion rate. Results: Tumour-infiltrating lymphocytes could be expanded to numbers that would be needed to generate a therapeutic infusion product from nine of 15 malignant specimens (60%). The CD4+ T cells predominated over CD8+ T cells (median 56.8% CD4+, 30.0% CD8+), and furthermore, faster TIL expansion was associated with a higher proportion of CD4+ T cells (median 69.8% in faster-growing cultures; 36.8% in slower-growing cultures). A higher proportion of CD3-CD56+ cells versus CD3+ cells was associated with slower TIL expansion in cultures from malignant specimens (median 13.3% in slower-growing cultures versus 2.05% in faster-growing cultures), but not from nonmalignant specimens. Conclusions: The expansion of TILs for potential therapeutic use is feasible. Our findings also indicate that further examination of TILs from prostate adenocarcinomas may yield insights into mechanisms of regulation of T cells within the tumour microenvironment. Further research is required to evaluate their therapeutic potential.

Salvage partial gland ablation for recurrent prostate cancer following primary partial gland ablation: Functional and oncological outcomes.

INTRODUCTION AND OBJECTIVE: Partial gland ablation (PGA) for localised prostate cancer (CaP) aims to eradicate clinically significant tumours while preserving healthy tissue, thereby decreasing the likelihood of side effects compared to whole-gland approaches. Although salvage radical prostatectomy (sRP) is a well-described salvage option in cases of PGA failure, the evidence supporting salvage PGA (sPGA) is limited. We hereby report the oncologic and functional outcomes of patients treated with sPGA following initial treatment with primary PGA (pPGA). METHODS: We describe the findings of a retrospective review of patients who had a CaP recurrence after pPGA and then underwent sPGA, at 3 medical centers in Ontario, Canada, between 2005 and 2017. Oncological outcomes following sPGA were assessed for biochemical recurrence (BCR) and biopsy-proven recurrence (BPR). Functional outcomes were described using the international prostate symptom score (IPSS), international index of erectile function (IIEF), and rates of urinary incontinence (use of >1 pad/day). RESULTS: We identified 25 patients who underwent sPGA following pPGA (hemiablation in 48% and zonal ablation in 52% of the patients). The median length of time was 16.8 months (interquartile range [IQR] 14.0-19.1) from pPGA to sPGA and 47.06 months (IQR 19.9-171.3) from pPGA to date of last follow up. High intensity focused ultrasound (HIFU) was the only modality used in all patients. At baseline, the median age was 65 years (IQR 52-77) and median prostate specific antigen (PSA) level was 7.46 ng/mL (IQR 1-25). The median time from pPGA to BPR was 12.7 months (IQR 5.19-36). At BPR following pPGA, 4 patients (17%) had CaP grade group (GG) 1, 10 patients (42%) had GG2, 6 patients (25%) had GG3, and 4 patients (17%) had GG4 disease, with a median PSA of 3.58 ng/mL (IQR 0.67-19). The median length of follow up after sPGA was 27.3 months (IQR 14.5-86.3). Following sPGA, 13/25 patients (52%) had BCR with median time to recurrence of 14 months (IQR 2.5-82.15), with a recurrence-free survival of 24.5 months (95% confidence interval: 15.3-not reached). Of those 13 patients, 4 were managed with sRP, 4 were managed with salvage radiotherapy, 3 were managed with androgen-deprivation therapy, 1 had a third PGA with HIFU, and 1 was managed with active surveillance. The mean change from baseline to last follow up in IPSS and IIEF scores was +1.3 (P = 0.66) and -2.3 (P = 0.32), respectively. Urinary incontinence was reported by 9% of patients at baseline, with only one additional patient developing incontinence following sPGA. CONCLUSION: Our present study demonstrates that after a median follow-up of 27 months, sPGA for recurrent CaP following pPGA provides disease control in up to 50% of patients with nonsignificant detrimental effects on functional outcomes. Appropriate patient selection and adequate staging are important to consider before offering PGA to patients.

Variability in testosterone measurement between radioimmunoassay (RIA), chemiluminescence assay (CLIA) and liquid chromatography-tandem mass spectrometry (MS) among prostate cancer patients on androgen deprivation therapy (ADT).

INTRODUCTION & AIMS: Monitoring testosterone (T) levels is recommended to assess the effectiveness of androgen deprivation therapy (ADT) in advanced prostate cancer. T levels below 20 ng/dL have been associated with better outcomes. Three main measures for T exist including radioimmunoassay (RIA), chemiluminescence assay (CLIA) and mass spectrometry (MS). While CLIA and RIA are ubiquitous, MS is regarded as the reference standard. We set out to determine the discordance of T measurements amongst men on ADT. METHODS: A retrospective review of men with prostate cancer on ADT for ≥3 months was conducted. Serum samples were split in triplicate. Observational data was reported and T measurements were compared analyzing for variability looking for categorical concordance. Over and under-estimation rates were calculated. RESULTS: Ninety-five patients were included with a mean age of 70 (50-92) years. Mean ADT duration was 24.1 (3-144) months. Ninety-five percent of patients had T ≤20ng/dL by MS and CLIA as compared to only 80% by RIA. After subdividing into T categories of ≤20, 20 to 50 and ≥50 ng/dL concordance analysis showed that 4.3% and 18.9% of T measured by MS would have a different category result when remeasured by CLIA (Kappa 0.84) or RIA (Kappa 0.50) respectively. CLIA and RIA overestimated T in 66.7% of patients with T <20 ng/dL measured by MS. Conversely CLIA and RIA underestimated T in only 4.4% of cases with T >20 ng/dL measured by MS. CONCLUSIONS: There is significant variability in T measured with RIA, CLIA and MS. CLIA and RIA overestimated T levels in majority of patients leaving a concern of misdiagnosing truly castrate patients as being inadequately treated.

Clinical Management of Prostate Cancer in High-Risk Genetic Mutation Carriers.

BACKGROUND: Prostate cancer is a leading cause of death. Approximately one in eight men who are diagnosed with prostate cancer will die of it. Since there is a large difference in mortality between low- and high-risk prostate cancers, it is critical to identify individuals who are at high-risk for disease progression and death. Germline genetic differences are increasingly recognized as contributing to risk of lethal prostate cancer. The objective of this paper is to review prostate cancer management options for men with high-risk germline mutations. METHODS: We performed a review of the literature to identify articles regarding management of prostate cancer in individuals with high-risk germline genetic mutations. RESULTS: We identified numerous publications regarding the management of prostate cancer among high-risk germline carriers, but the overall quality of the evidence is low. CONCLUSIONS: We performed a review of the literature and compiled clinical considerations for the management of individuals with high-risk germline mutations when they develop prostate cancer. The quality of the evidence is low, and there is an immediate need for further research and the development of consensus guidelines to guide clinical practice for these individuals.

The association of statin subgroups with lower urinary tract symptoms following a prostate biopsy.

INTRODUCTION: This was a secondary analysis aiming to assess whether hydrophilic or hydrophobic statins have a differential effect on urinary retention (UR) and lower urinary tract symptoms (LUTS) in men following a prostate biopsy (PBx), who were at risk for prostate cancer development. METHODS: This was a population-based cohort study with data incorporated from the Institute for Clinical and Evaluative Sciences database to identify all Ontarian men aged 66 and above with a history of a single negative PBx between 1994 and 2016, with no drug prescription history of any of several putative chemo-preventative medications (statins, proton pump inhibitors, five-alpha-reductase inhibitors, and alpha-blockers). Multivariable Cox regression models with time-dependent covariates were used to assess the association of hydrophilic and hydrophobic statins with UR and LUTS within 30 days of a PBx. All models were adjusted for other known putative chemopreventive medications, age, rurality, pharmacologically treated diabetes, comorbidity score, and study inclusion year. RESULTS: Overall, 21 512 men were included, with a median followup time of 9.4 years (interquartile range [IQR] 5.4-13.4 years). Hydrophobic and hydrophilic statins were initiated by 30.7% and 19.6% of men, respectively, after the first negative PBx. UR and LUTS were experienced by 2.2% and 10% of men, respectively. Cox models demonstrated hydrophilic statins were associated with a lower risk of UR (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.38-0.83, p=0.0038) and LUTS (HR 0.86, 95% CI 0.76-0.98, p=0.022), while no such association was shown for hydrophobic statins. CONCLUSIONS: Initiation of hydrophilic statins in men older than 66 appears to be inversely associated with the risk of UR and LUTS within 30 days of a PBx.

Time trends of drug-specific actionable adverse events among patients on androgen receptor antagonists: Implications for remote monitoring.

INTRODUCTION: In light of COVID-19, reducing patient exposure via remote monitoring is desirable. Patients prescribed abiraterone/ enzalutamide are scheduled for monthly in-person appointments to screen for adverse events (AEs). We determined time trends of drug-specific actionable AEs among users of abiraterone/enzalutamide to assess the safety of remote monitoring. METHODS: A chart review was conducted on 828 prostate cancer patients prescribed abiraterone and/or enzalutamide. Data were collected to determine time to actionable first AEs, including hypertension, elevated liver enzymes (aspartate transaminase [AST], alanine transaminase [ALT]), hyperbilirubinemia, and hypokalemia. Survival analysis was used to determine time to AEs. RESULTS: In this study, 425 and 403 patients received enzalutamide and abiraterone, respectively. In total, 25.6% of those who took enzalutamide experienced an AE, compared to 28.8% of patients on abiraterone. For patients using abiraterone and experiencing an AE, cumulative incidence of AEs at three, six, nine, and 12 months were: 67.2%, 81.9%, 90.5%, and 93.9%, respectively. Among enzalutamide users experiencing an AE, cumulative incidence of AEs at three, six, nine, and 12 months were 51.4%, 70.7%, 82.6%, and 88.1%, respectively. The AEs associated with enzalutamide were hypertension and liver dysfunction (77.1% and 22.9%, respectively). In the abiraterone group, associated AEs were liver dysfunction (47.4%), hypertension (47.4%), and hypokalemia (5.2%). CONCLUSIONS: Attaining AEs secondary to abiraterone/enzalutamide decreases over time and tends to occur within the first six months of therapy. Most actionable AEs can be remotely monitored. Given COVID-19, remote monitoring after six months of initiating abiraterone or enzalutamide appears appropriate.

Biorepositories and Databanks for the Development of Novel Biomarkers for Genitourinary Cancer Prevention and Management.

CONTEXT: Translational research in uro-oncology depends on the availability of high-quality biospecimens and associated data to advance precision medicine and improve clinical outcomes. Procurement, storage, and annotation of these specimens represent critical steps towards this end. OBJECTIVE: To review best-practice experiences gained via the McCain GU BioBank, a repository of more than 750 000 biospecimens obtained from more than 16 000 patients attending clinics at the University Health Network in Toronto, Canada. EVIDENCE ACQUISITION: The review summarizes our experiences at a large single-institution genitourinary oncology biorepository. EVIDENCE SYNTHESIS: Key findings are placed in the context of emerging trends in genitourinary oncology, with a focus on integration of molecular profiling and clinical data with traditional biorepository management. Proposed approaches provide high-quality biospecimens with comprehensive and reliable clinical data that can fuel innovation and discovery in research. CONCLUSIONS: Biorepositories are vital for improving clinical outcomes and advancing personalized medicine. High-quality biospecimens and their associated clinical data are crucial for validation of biomarkers in oncology. Efforts to procure, store, and annotate clinical specimens represent critical steps in translational research. Elements such as biobank size, biospecimen types, disease cohorts, predetermined collection protocols, broad informed consent, sample handling and storage protocols, and available infrastructure directly influence the effectiveness and capacity of a biobank. PATIENT SUMMARY: Biorepositories, or biobanks, are facilities that store biospecimens such as blood, urine, or tissue (usually collected from humans) for use in research. Biobanks have become an important resource in medical research, as they provide high-quality specimens to support different types of contemporary research such as genomics, biomarker discovery, and personalized medicine. Clinical management and treatment of genitourinary cancers, such as prostate, kidney, and bladder cancers, are particularly suited for biomarker research. The provision of biospecimens and their associated clinical data have become crucial for validation of biomarkers in these cancers.

The evolving role of germline genetic testing and management in prostate cancer: Report from the Princess Margaret Cancer Centre international retreat.

Prostate cancer is a significant cause of cancer mortality. It has been well-established that certain germline pathogenic variants confer both an increased risk of being diagnosed with prostate cancer and dying of prostate cancer.1 There are exciting developments in both the availability of genetic testing and opportunities for improved treatment of patients.On August 19, 2020, the Princess Margaret Cancer Centre in Toronto, Ontario, hosted a virtual retreat, bringing together international experts in urology, medical oncology, radiation oncology, medical genetics, and translational research, as well as a patient representative. We are pleased to provide this manuscript as a review of those proceedings for Canadian clinicians.We highlighted several needs for future research and policy action based on this meeting:Increased access to funding for germline testing for the common genetic disorders associated with increased risk of prostate cancer.More research into identifying genetic factors influencing risk stratification, treatment response, and outcomes of prostate cancer within Canadian populations at higher genetic risk for prostate cancer.Added awareness about genetic risk factors among the Canadian public.Development of patient-specific and reported outcomes research in tailored care for patients at increased genetic risk of prostate cancer.Creation of multidisciplinary clinics that specialize in tailored care for patients at increased genetic risk of prostate cancer.

The suggested chemopreventive association of metformin with prostate cancer in diabetic patients.

PURPOSE: Metformin, an insulin sensitizer, is the most common first-line antidiabetic therapy. There is increasing evidence suggesting metformin can prevent the emergence of prostate cancer (CaP). We aimed to analyze the chemopreventive role of metformin, in conjunction with other putative chemopreventive medications (statins, proton-pump-inhibitors, alpha-blockers, 5-alpha-reductase inhibitors, diabetic medications) in a population-based cohort study. METHODS: Data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all diabetic men aged 66 and above with prior history of a negative prostate biopsy (PB) between 1994 and 2016, who were not on any of the medications prior to study inclusion. Multivariable Cox regression models with time-dependent covariates were used to assess the association of metformin to CaP diagnosis, subsequent PB, and use of androgen deprivation therapy (ADT). All models were adjusted for age, rurality, comorbidity, and year of study inclusion. RESULTS: Overall, 2,332 diabetic men were included, with a median follow-up time of 9.4 years (interquartile range 5.4-13.4 years). A total of 2,036 patients (87.3%) received metformin. Compared to non-metformin users, metformin use was associated with decreased CaP diagnosis rate (HR 0.69, 95%CI 0.54-0.88, P = 0.003), lower hazard of undergoing an additional PB (HR 0.64, 95%CI 0.44-0.95, P = 0.03), and receiving ADT (HR 0.72, 95%CI 0.54-0.96, P = 0.003). CONCLUSION: Men receiving metformin were less likely to have suspected or diagnosed CaP, and in those with CaP, the use of ADT was less common. Ongoing prospective randomized studies will determine if these findings correspond to the suggested associations of metformin in the emergence and/or progression of CaP.

The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer.

BACKGROUND: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins. OBJECTIVE: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models. RESULTS AND LIMITATIONS: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies. CONCLUSIONS: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration. PATIENT SUMMARY: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.

The deleterious association between proton pump inhibitors and prostate cancer-specific mortality - a population-based cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort. METHODS: We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year. RESULTS: Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis. CONCLUSIONS: Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

Optimizing screening and management of cardiovascular health in prostate cancer: A review.

In clinical practice, cancer management does not consistently encompass screening and identification of cardiovascular (CV) risk. The use of androgen deprivation therapy (ADT) in prostate cancer has been associated with increased CV risk and development of metabolic syndrome, necessitating identification of patients at risk in this population (e.g., those with pre-existing CV disease). A multidisciplinary team of Canadian physicians was assembled to develop a series of recommendations intended to identify patients who may benefit from optimal management of their CV disease and/or modification of cardiac risk factors. A key goal was the development of a simple screening tool for identification of patients with pre-existing CV disease. This simple and inclusive set of recommendations are intended for use within urology clinics to facilitate holistic approaches and simplify the management of patients.

A Prospective Randomized Controlled Trial of Irrigation "Bag Squeeze" to Manage Pain for Patients Undergoing Flexible Cystoscopy.

PURPOSE: We determined if the "bag squeeze" technique decreases pain during flexible cystoscopy in men. MATERIALS AND METHODS: This single center, prospective, double-blind, randomized controlled trial recruited 200 consenting participants who were ambulatory, outpatient males who had undergone prior cystoscopy and were not expected to require any secondary procedures. Men with prior urethral stricture or bladder neck contracture were excluded from study. Once eligibility was assessed and consent obtained, participants were randomized to undergo cystoscopy with the bag squeeze (group A) or the sham bag squeeze procedure (group B). Following cystoscopy, participants completed a pain questionnaire (visual analogue scale). Differences in mean pain score between groups were evaluated using Students' t-test with a 2-sided alpha of 0.05. RESULTS: A total of 200 patients were randomized and underwent flexible cystoscopy. Ten participants were ineligible because they required secondary procedures. Among the 190 eligible patients 97 were randomized to bag squeeze (group A) and 93 to sham bag squeeze (group B) with mean pain scores of 1.91 and 3.39, respectively (p <0.005). CONCLUSIONS: This study demonstrated a clinically meaningful decrease in pain for men undergoing flexible cystoscopy when the irrigation bag squeeze technique was used vs placebo bag squeeze. Accordingly, this useful, simple and free method to improve patient comfort during flexible cystoscopy should be adopted by clinicians.

Preliminary data indicating a connection between stress-induced prefrontal dopamine release and hippocampal TSPO expression in the psychosis spectrum.

Prolonged stress can cause neuronal loss in the hippocampus resulting in disinhibition of glutamatergic neurons proposed to enhance dopaminergic firing in subcortical regions including striatal areas. Supporting this, imaging studies show increased striatal dopamine release in response to psychosocial stress in healthy individuals with low childhood maternal care, individuals at clinical high risk for psychosis (CHR) and patients with schizophrenia. The prefrontal cortex (PFC) is connected to the hippocampus and a key region to control neurochemical responses to stressful stimuli. We recently reported a disrupted PFC dopamine-stress regulation in schizophrenia, which was intact in CHR. Given the available evidence on the link between psychosocial stress, PFC dopamine release and hippocampal immune activation in psychosis, we explored, for the first time in vivo, whether stress-induced PFC dopamine release is associated with hippocampal TSPO expression (a neuroimmune marker) in the psychosis spectrum. We used an overlapping sample of antipsychotic-naïve subjects with CHR (n = 6) and antipsychotic-free schizophrenia patients (n = 9) from our previously published studies, measuring PFC dopamine release induced by a psychosocial stress task with [11C]FLB457 positron emission tomography (PET) and TSPO expression with [18F]FEPPA PET. We observed that participants on the psychosis spectrum with lower stress-induced dopamine release in PFC had significantly higher TSPO expression in hippocampus (ß = -2.39, SE = 0.96, F(1,11) = 6.17, p = 0.030). Additionally, we report a positive association between stress-induced PFC dopamine release, controlled for hippocampal TSPO expression, and Global Assessment of Functioning. This is the first exploration of the relationship between PFC dopamine release and hippocampal TSPO expression in vivo in humans.

Impaired Prefrontal Cortical Dopamine Release in Schizophrenia During a Cognitive Task: A [11C]FLB 457 Positron Emission Tomography Study.

Evidence from several lines of research suggests decreased dopamine release in the prefrontal cortex as the neurochemical correlates of cognitive deficits in schizophrenia (SCZ). However, in vivo examination of cortical hypodopaminergia using positron emission tomography (PET) during cognitive task performance in SCZ remains to be investigated. We examined dopamine release in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), using PET while participants were performing a cognitive task. Thirteen drug-free patients with SCZ and 13 healthy volunteers (HV) matched for age and sex participated in the study. Data were acquired between 2011 and 2015. Two PET scans with [11C]FLB 457 were acquired while the participants were performing the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task (SMCT). A magnetic resonance image was acquired for anatomical delineation. Differences in cortical dopamine release between SCZ and HV, indexed as percentage change in binding potential between WCST and SMCT (ΔBPND), were calculated in ACC and DLPFC. We observed significant differences in the ΔBPND in ACC (HV = 4.40 ± 6.00; SCZ = -11.48 ± 15.08; t = 3.52; P = .003) and a trend-level difference in ΔBPND in DLPFC (HV = -0.58 ± 8.45; SCZ = -7.79 ± 11.28; t = 1.84; P = .079), suggesting dopamine depletion in cortical brain regions in patients with SCZ while performing a cognitive task. These results provide the first in vivo evidence for reduced dopamine release or even dopamine depletion while performing cognitive task in ACC and DLPFC in patients with SCZ. The present results provide support for the frontal hypodopaminergia hypothesis of cognitive symptoms in SCZ.