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OBJECTIVES: To quantify the real-world survival benefit of re-resection vs no re-resection in patients diagnosed with T1 bladder cancer (BC) at the population level. PATIENTS AND METHODS: Retrospective population-wide observational cohort study based on pathology reports linked to health administrative data. We identified patients who were diagnosed with T1 BC in the province of Ontario (01/2001-12/2015) and used billing claims to ascertain whether they received re-resection within 2-10 weeks. The time-dependent effect of re-resection on survival outcomes was modelled by Cox proportional hazards regression (unadjusted and adjusted for numerous assumed patient- and surgeon-level confounding variables). Effect measures were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 7666 patients of which 2162 (28.7%) underwent re-resection after a median (interquartile range) time of 45 (35-56) days. Patients who received re-resection were less likely to die from any causes (HR 0.68, 95% CI 0.63-0.74, P

BACKGROUND The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect). METHODS Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect). RESULTS Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75). CONCLUSIONS Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.

Summary Background Mortality in acute respiratory failure remains high despite the use of lung-protective ventilation. Recent studies have shown an association between baseline ventilation parameters (driving pressure or mechanical power) and outcomes for patients with acute respiratory distress syndrome. Strategies focused on limiting these parameters have been proposed to further improve outcomes. However, it remains unknown whether driving pressure and mechanical power should be limited over the entire duration of mechanical ventilation and in all patients with acute respiratory failure. We aimed to estimate the association between exposure to different intensities of mechanical ventilation over time and intensive care unit (ICU) mortality in patients with acute respiratory failure. Methods In this registry-based, prospective cohort study, we obtained data from the Toronto Intensive Care Observational Registry, which includes all patients receiving mechanical ventilation for 4 h or more in nine ICUs that are affiliated with the University of Toronto (Toronto, ON, Canada). We included all adult (≥18 years) patients who received invasive mechanical ventilation between April 11, 2014, and June 5, 2019. Patients were excluded if they received treatment with extracorporeal life support. The primary outcome was ICU mortality. Bayesian joint models were used to estimate the strength of associations, accounting for informative censoring due to death during follow-up. Findings Of 13 939 patients recorded in the registry, 13 408 (96·2%) were eligible for descriptive analysis. The primary analysis comprised 7876 (58·7%) patients with complete baseline characteristics, and a secondary analysis included all 13 408 patients after multiple imputation in the joint model analysis. 2409 (18·0%) of 13 408 patients died in the ICU. After adjustment for baseline characteristics, including age and severity of illness, a significant increase in the hazard of death was found to be associated with each daily increment in driving pressure (hazard ratio 1·064, 95% credible interval 1·057–1·071) or mechanical power (hazard ratio 1·060, 95% credible interval 1·053–1·066). These associations persisted over the duration of mechanical ventilation. Interpretation Cumulative exposure to higher intensities of mechanical ventilation was harmful, even for short durations. Limiting exposure to driving pressure or mechanical power should be evaluated in further studies as promising ventilation strategies to reduce mortality in patients with acute respiratory failure. Funding Canadian Institutes of Health Research.

Background Single‐arm trials are currently an accepted study design to investigate the efficacy of novel therapies (NT) in non‐muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) immunotherapy as randomized controlled trials are either unfeasible (comparator: early radical cystectomy; ERC), or unethical (comparator: placebo). To guide the design of such single‐arm trials, expert groups published recommendations for clinically meaningful outcomes. The aim of this study was to quantitatively verify the appropriateness of these recommendations. Methods We used a discrete event simulation framework in combination with a supercomputer to find the required efficacy at which a NT can compete with ERC when it comes to quality‐adjusted life expectancy (QALE). In total, 24 different efficacy thresholds (including the recommendations) were investigated. Results After ascertaining face validity with content experts, repeated verification, external validation, and calibration we considered our model valid. Both recommendations rarely showed an incremental benefit of the NT over ERC. In the most optimistic scenario, an increase in the IBCG recommendation by 10% and an increase in the FDA/AUA recommendation by 5% would yield results at which a NT could compete with ERC from a QALE perspective. Conclusions This simulation study demonstrated that the current recommendations regarding clinically meaningful outcomes for single‐arm trials evaluating the efficacy of NT in BCG‐unresponsive NMIBC may be too low. Based on our quantitative approach, we propose increasing these thresholds to at least 45%‐55% at 6 months and 35% at 18‐24 months (complete response rates/recurrence‐free survival) to promote the development of clinically truly meaningful NT., Expert groups published recommendations regarding clinically meaningful outcomes for single‐arm trials evaluating the efficacy of novel therapies in BCG‐unresponsive non‐muscle invasive bladder cancer. In this study, we used a discrete event simulation framework in combination with a supercomputer to demonstrate that these recommendations do probably not reflect clinically meaningful outcomes and should be increased to at least 45%‐55% at 6 months and 35% at 18‐24 months (complete response rates/recurrence‐free survival).

Prior research has shown that concordance with the guideline-endorsed recommendation to re-resect patients diagnosed with primary T1 bladder cancer (BC) is suboptimal. Therefore, the aim of this population-based study was to identify factors associated with re-resection in T1 BC.We linked province-wide BC pathology reports (January 2001 to December 2015) with health administrative data sources to derive an incident cohort of patients diagnosed with T1 BC in the province of Ontario, Canada. Re-resection was ascertained by a billing claim for transurethral resection within 2 to 8 weeks after the initial resection, accounting for system-related wait times. Multivariable logistic regression analysis accounting for the clustered nature of the data was used to identify various patient-level and surgeon-level factors associated with re-resection. P values0.05 were considered statistically significant (2-sided).We identified 7,373 patients who fulfilled the inclusion criteria. Overall, 1,678 patients (23%) underwent re-resection. Patients with a more aggressive tumor profile and individuals without sufficiently sampled muscularis propria as well as younger, healthier and socioeconomically advantaged patients were more likely to receive re-resection (all p0.05). In addition, more senior, lower volume and male surgeons were less likely to perform re-resection for their patients (all p0.05).Only a minority of all patients received re-resection within 2 to 8 weeks after initial resection. To improve the access to care for potentially underserved patients, we suggest specific knowledge translation/exchange interventions that also include equity aspects besides further promotion of evidence-based instead of eminence-based medicine.

INTRODUCTION AND OBJECTIVE:A second transurethral resection within 2 to 6 weeks after the initial resection (i.e. re-resection) is recommended for patients diagnosed with primary T1 bladder cancer ...

INTRODUCTION AND OBJECTIVE:Accurate diagnosis in men with suspected prostate cancer (PC) is essential when several alternative treatment options to radical prostatectomy (RP) such as active surveil...

BACKGROUND MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. METHODS We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. CONCLUSIONS MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

A second transurethral resection of the bladder tumor (TURBT) within 2 - 6 weeks after initial TURBT is thought to have diagnostic, therapeutic, and prognostic benefits in T1 bladder cancer (BC). However, little is known about the real-world uptake of this guideline-endorsed intervention. We aimed (1) to measure re-resection rates over time, (2) to investigate if a guideline revision (April 2008) explicitly endorsing re-resection within 2 - 6 weeks in all T1 BC patients led to an increase in re-resection rates, and (3) to investigate the uptake among different groups of surgeons.Province-wide BC pathology reports (January 2001 to December 2015; Ontario, Canada) were linked with health administrative data to (1) identify primary cases of T1 BC and to (2) ascertain whether these patients received re-resection. The resulting patients were then aggregated into quarterly time series and investigated by descriptive analysis, interventional autoregressive moving average (ARIMA) modeling, and Poisson regression analysis.A cohort of 7,373 patients was aggregated into a time series. We observed a linear increase in re-resection rates from 8.4% in 2001 to 28.3% in 2015. An actual effect of the guideline revision in April 2008 on re-resection rates could not be detected (P = 0.41). However, we observed a rather heterogeneous uptake behavior among different groups of surgeons. Specifically, female surgeons, more junior surgeons, high-volume surgeons, Canadian graduates, and surgeons without an academic affiliation were all independently more likely to re-resect their patients (all P-values0.05 in adjusted analysis).Re-resection rates in primary T1 BC increased between 2001 and 2015 in the province of Ontario regardless of the guideline revision in April 2008. Our study demonstrates that the uptake of this guideline-endorsed intervention varies among different groups of surgeons and therefore warrants further research to identify barriers to change that can be addressed by tailored interventions.

Transurethral resection of bladder tumors (TURBT) represents the cornerstone in diagnosis and treatment of bladder cancer but recurrence is observed in up to 80% and over- or understaging with TURBT is common. A more recent development to overcome these limitations represents en-bloc resection of bladder tumors (ERBT) which offers several advantages over TURBT. In this report, we briefly review studies assessing outcomes of bladder cancer patients undergoing ERBT. Most randomized and non-randomized trial demonstrate improvement in clinical outcomes for ERBT over TURBT, however more pathological and translational studies are warranted.

Importance Microhematuria (MH) is a common finding that often leads to further evaluation for urinary tract cancers. There is ongoing debate about the extent to which patients with MH should be evaluated for cancer. Objective To assess the diagnostic yield for detection of urinary tract cancers, specifically bladder cancer, upper tract urothelial carcinoma (UTUC), and kidney cell carcinoma, among patients evaluated for MH using cystoscopy and computed tomographic (CT) urography. Data Sources MEDLINE, Scopus, and Embase were systematically searched for eligible studies published between January 1, 2009, and December 31, 2019. Study Selection Original prospective and retrospective studies reporting the prevalence of cancer among patients evaluated for MH were eligible. Two authors independently screened the titles and abstracts to select studies that met the eligibility criteria and reached consensus about which studies to include. Among 5802 records identified, 5802 articles were screened using titles and abstracts. After exclusions, 55 full-text articles were assessed for eligibility, with 39 studies selected for systematic review. Data Extraction and Synthesis This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Studies were quantitatively synthesized using a random-intercept logistic regression model. Main Outcomes and Measures The primary outcome was diagnostic yield, defined as the proportion of patients with a diagnosis of urinary tract cancer (bladder cancer, UTUC, or kidney cell carcinoma) after presentation with MH. Studies were stratified by the percentage of cystoscopy and CT urography use and by high-risk cohorts. The diagnostic yields of CT urography and cystoscopy were calculated for each cancer type. Results A total of 30 studies comprising 24 366 patients evaluated for MH were included in the meta-analysis. The pooled diagnostic yield among all patients was 2.00% (95% CI, 1.30%-3.09%) for bladder cancer, 0.02% (95% CI, 0.0%-0.15%) for UTUC, and 0.18% (95% CI, 0.09%-0.36%) for kidney cell carcinoma. Stratification of studies that used cystoscopy and/or CT urography for 95% or more of the cohort produced diagnostic yields of 2.74% (95% CI, 1.81%-4.12%) for bladder cancer, 0.09% (95% CI, 0.01%-0.75%) for UTUC, and 0.10% (95% CI, 0.04%-0.23%) for kidney cell carcinoma. In high-risk cohorts, the diagnostic yields increased to 4.61% (95% CI, 2.34%-8.90%) for bladder cancer and 0.45% (95% CI, 0.22%-0.95%) for UTUC. Conclusions and Relevance This study’s findings suggest that, given the low diagnostic yield of CT urography and the associated risks and costs, limiting its use to high-risk patients older than 50 years is warranted. Risk stratification, as recommended by the recent American Urology Association guidelines on MH, may be a better approach to tailor further evaluation.

Introduction: Prior research demonstrated an association between surgical case volume and survival in muscle-invasive bladder cancer (BC). This relationship, however, has not been investigated in the setting of T1 BC so far. Therefore, we investigated whether a higher surgical case volume of T1 BC translates into improved survival outcomes. Methods: Province-wide pathology reports (January 2002 to December 2015) were linked with health administrative data to identify patients diagnosed with T1 BC. For each patient, we determined the T1 case volume of the involved surgeon by benchmarking (percentile) her/him against his/her colleagues during a lookback period of one year. The volume-outcome (overall survival) relationship was then investigated by Cox proportional hazards regression (unadjusted and adjusted for a wide range of assumed confounders) that incorporated volume in three different ways (80th percentile and higher vs. below, median and higher vs. below, continuous [quintiles]). Effect sizes were presented as hazard ratios (95% confidence interval). Results: We identified 7426 patients who were diagnosed with T1 BC and followed for 4.8 years. A third of all patients (n=1895, 25.5%) received surgery by a high-volume surgeon (80th percentile and higher). Higher T1 case volume was associated with improved survival both in unadjusted (80th percentile: 0.93 [0.86–0.99]; median: 0.93 [0.87–0.99]; continuous: 0.97 [0.94–0.99]) and adjusted analysis (80th percentile: 0.94 [0.88–1.01]; median: 0.93 [0.87–0.99]; continuous: 0.97 [0.95–0.99]). Conclusions: This province-wide cohort study could demonstrate a volume-outcome relationship in T1 BC and raises questions regarding the regionalization of care in high-risk non-muscle-invasive BC. The generalizability of our findings, however, is limited by the fact that the performance of the initial resection by a high-volume surgeon does not necessarily translate into downstream care by the same surgeon.

Objective To review the indications for and side effects of androgen deprivation therapy (ADT) in men affected by prostate cancer. Data Sources National guidelines, evidence-based summaries, peer-reviewed studies, and websites. Conclusion Indications for ADT include men with (1) intermediate- to high-risk localised prostate cancer undergoing radiation therapy, (2) biochemical recurrence after radical prostatectomy treated with salvage radiation therapy, or (3) metastatic prostate cancer. Several forms of ADT are available. To support self-management, body weight, diet, physical activity, alcohol consumption, and smoking should be discussed during clinical consultations. Important side effects of ADT may include flare-up phenomena of GnRH analogues, local reactions at injection sites, cardiovascular events, bone loss/fractures, drug-drug interactions, urinary tract dysfunction, hot flashes, cognitive impairment, seizure falls, and liver impairment. Implications for Nursing Practice Nurses have a role in personalized cancer care and should be familiar with indications, side effects, and interventions to optimize quality of life for men affected by prostate cancer receiving ADT.

With the current movement toward treating oligometastatic hormone sensitive prostate cancer (OMPC), we design a study with the objective of gathering opinions regarding what would be considered a clinically significant benefit from such treatments.Data was collected from physicians of the Society of Urologic Oncology using a self-administered questionnaire using SurveyMonkey. The questionnaire was designed to obtain characteristics on clinical practice of the respondents, definitions used for OMPC and also what would be considered a clinically significant benefit according to the respondents. We present a descriptive analysis of the responses obtained.We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected "clinically-significant" benefit.This study shows that most clinicians still support the use of conventional imaging to define OMPC. Our findings show that a curing rate of a minimum of 11% and an androgen deprivation therapy-free survival at 1 year are considered clinically significant and this should be used for estimating the sample size in future clinical trials.

Background and objectives The general rule that every active malignancy is an absolute contraindication for kidney transplantation is challenged by kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. Interdisciplinary treatment teams therefore often face the challenge of balancing the benefits of early kidney transplantation and the risk of metastatic progression. Hence, we compared the quality-adjusted life expectancy of different management strategies in kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. Design, setting, participants, & measurements A discrete event simulation model was developed on the basis of a systematic literature search, clinical guidelines, and expert opinion. After model validation and calibration, we simulated four management strategies in a hypothetical cohort of 100,000 patients: Definitive treatment (surgery or radiation therapy) and listing after a waiting period of 2 years, definitive treatment and immediate listing, active surveillance and listing after a waiting period of 2 years, and active surveillance and immediate listing. Individual patient results (quality-adjusted life years; QALYs) were aggregated into strategy-specific means (± SEs). Results Active surveillance and immediate listing yielded the highest amount of quality-adjusted life expectancy (6.97 ± 0.01 QALYs) followed by definitive treatment and immediate listing (6.75 ± 0.01 QALYs). These two strategies involving immediate listing not only outperformed those incorporating a waiting period of 2 years (definitive treatment: 6.32 ± 0.01 QALYs; active surveillance: 6.59 ± 0.01 QALYs) but also yielded a higher proportion of successfully performed transplantations (72% and 74% versus 56% and 59%), with less time on hemodialysis on average (4.02 and 3.81 years versus 4.80 and 4.65 years). Conclusions Among kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup, the active surveillance and immediate listing strategy outperformed the alternative management strategies from a quality of life expectancy perspective, followed by definitive treatment and immediate listing.

Highly sensitive and specific urinary biomarkers for the early detection of bladder cancer (BC) to improve the performance of urinary cytology are needed.To investigate the usefulness of methylation markers in voided urine to identify BC presence and grade.Using genome-wide methylation strategies in Toronto, Canada and Liège, Belgium, we have identified differentially methylated genes (TWIST1, RUNX3, GATA4, NID2, and FOXE1) in low-grade vs. high-grade BC tissue and urine. We accrued urine samples from 313 patients using a 2:1 ratio in a case-control setting from Toronto, Canada, Halifax, Canada, and Zurich, Switzerland. We studied the usefulness of these 5 methylated genes to identify BC and discriminate cancer grade in voided urine specimens. Urinary cell sediment DNA was evaluated using qPCR-based MethyLight assay. Multivariable logistic regression prediction models were created.We included 211 BC patients (180 nonmuscle invasive) and 102 controls. In univariate analyses, all methylated genes significantly predicted BC vs. no BC, and high grade vs. low grade (all P0.05). In multivariable analysis, NID2, TWIST1, and age were independent predictors of BC (all P0.05). Sensitivity of NID2 and TWIST1 to predict BC and BC grade was 76.2% and 77.6%, respectively, whereas specificity was 83.3% and 61.1%, respectively. Multivariable models predicting BC overall and discriminating between high-grade and low-grade BC reached area under the receiver operating characteristics curves of 0.89 and 0.78, respectively.This multi-centric study in a real life scenario (different countries, techniques, and pathologists) supports the promise of epigenetic urinary markers in noninvasively detecting BC. With sensitivities and specificities in the range of 80%, the overall performance characteristics of this panel of methylated genes probably does not allow such signature to significantly alter clinical care at this stage but is worth further studying for instance in BC surveillance or screening in high-risk populations.

Purpose:Leydig cell tumors are rare but they are the most common nongerm cell testicular tumors. Only limited evidence exists for reliably differentiating between benign and malignant Leydig cell t...

Introduction: Digital rectal examination (DRE) is part of the clinical evaluation of men on active surveillance (AS). The purpose of the present study is to analyze the value of DRE as a predictor of upgrading in a population of men with prostate cancer (PCa) treated with AS. Methods: We used the prostate biopsy (PBx) database from an academic center, including PBx from 2006–2018, and identified 2029 confirmatory biopsies (CxPBx) of men treated with AS, of which 726 men had both diagnostic (initial) and CxPBx information available. We did a descriptive analysis and evaluated sensitivity, specificity, and predictive values of DRE for the detection of clinically significant PCa (csPCa). Multivariable regression analysis was done to identify predictors of csPCa. The primary outcome was to evaluate DRE as a predictor of the presence of csPCa at CxPBx. Results: Among the 2029 patients with a CxPBx, 75% had PCa, and of these, 30.3% had upgrading to International Society of Urologic Pathologists (ISUP) grade ≥2. Thirteen percent of men had a suspicious DRE (done by their treating physician). Sensitivity, specificity, negative and positive predictive values of DRE to detect csPCa were best with a prostate-specific antigen (PSA)

To investigate whether heat-induced fiber degradation and loss of power output, which occurred during GreenLight laser vaporization (LV) of the prostate using the first- and second-generation 80 and 120 W laser, are still an issue during LV using the upgraded third generation 180 W GreenLight XPS™ laser. Laser beam power output of 53 laser fibers was measured at baseline and after every 25 kJ of delivered energy during routine 180 W GreenLight XPS™ LV in 47 patients with prostatic bladder outflow obstruction. After the procedures, the fiber tips were microscopically examined. The median applied energy per patient was 178 kJ [interquartile range (IQR): 106–247]. Loss of power output during the procedure was detectable in all fibers. After the application of 25, 150, and 250 kJ, the median power output decreased to 77% (IQR 59–87), 57% (IQR 32–71), and 51% (IQR 37–64) of the baseline value. Nine fibers (17%) remained on a relatively high power output level (> 80% of the initial output), while 13 fibers (25%) showed an end-of-procedure power output of less than 20%. Microscopy of the fiber tip revealed mild-to-moderate overall degradation and increasing degradation with higher energy delivered. Despite changes in fiber design, heat-induced fiber damage and loss of power output remain an issue during 180 W GreenLight XPS™ LV. Whether modifications of the surgical technique can prevent impairment of fiber performance needs to be further evaluated.

BACKGROUND The prognostic role of preoperative serum lipid levels in patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer (PCa) is unclear. The aim of the present study was to investigate preoperative serum lipid levels in patients with clinically localized PCa undergoing RP and their association with clinicopathological features and oncological outcome. METHODS Preoperative lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) and statin use from consecutive patients with clinically localized PCa undergoing RP in a tertiary referral center between 2008 and 2015 were recorded and patients were followed prospectively. Logistic regression analysis was used to test the association between lipid levels and clinicopathological parameters. Lipid values were analyzed both as continuous and dichotomized variables. Univariable and multivariable Cox regression analyses were performed to identify predictors for recurrence-free survival (RFS). Recurrence was defined as rising and verified PSA levels >0.1 ng/ml. RESULTS Our cohort consisted of 371 men with a median age of 63 years (range 41-78 years) and a median preoperative PSA value of 6.79 ng/ml (0.43-81.4 ng/ml). Median follow-up was 28 months (1-64). No association was found between lipid levels and adverse pathological characteristics such as ≥pT3, Gleason score ≥8, positive nodal status and positive surgical margins. Recurrence occurred in 49 patients (15.4%) at a median time of 18 months (2-51 month). Compared to low LDL cholesterol, high LDL cholesterol was associated with longer RFS in univariable analysis (continuous: Hazard Ratio (HR): 0.67, 95%-Confidence Interval (CI): 0.47-0.96, P = 0.03; 3 mM cut-point: HR: 0.44, 95%-CI: 0.24-0.79, P = 0.006). Neither levels of other lipids, nor statin use were associated with RFS. Preoperative LDL cholesterol remained an independent predictor for PCa recurrence in a multivariable model adjusted for age, preoperative PSA, statin use, tumor stage, Gleason score, nodal status and surgical margin status (continuous: HR: 0.66, 95%-CI: 0.44-0.99, P = 0.04; 3 mM cut-point: HR: 0.41, 95%-CI: 0.21-0.78, P = 0.007). CONCLUSIONS This is the first prospective study showing the potential adverse and independent prognostic role of low preoperative LDL cholesterol levels in patients with localized PCa undergoing RP. Prostate © 2017 Wiley Periodicals, Inc.

We sought to externally validate recently published prostate cancer risk calculators incorporating multiparametric magnetic resonance imaging to predict clinically significant prostate cancer. We also compared the performance of these calculators to that of multiparametric magnetic resonance imaging naïve prostate cancer risk calculators.We identified men without a previous prostate cancer diagnosis who underwent transperineal template saturation prostate biopsy with fusion guided targeted biopsy between November 2014 and March 2018 at our academic tertiary referral center. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. Predictors, which were patient age, prostate specific antigen, digital rectal examination, prostate volume, family history, previous prostate biopsy and the highest region of interest according to the PI-RADS™ (Prostate Imaging Reporting and Data System), were retrospectively collected. Four multiparametric magnetic resonance imaging prostate cancer risk calculators and 2 multiparametric magnetic resonance imaging naïve prostate cancer risk calculators were evaluated for discrimination, calibration and the clinical net benefit using ROC analysis, calibration plots and decision curve analysis.Of the 468 men 193 (41%) were diagnosed with clinically significant prostate cancer. Three multiparametric magnetic resonance imaging prostate cancer risk calculators showed similar discrimination with a ROC AUC significantly higher than that of the other prostate cancer risk calculators (AUC 0.83-0.85 vs 0.69-0.74). Calibration in the large showed 2% deviation from the true amount of clinically significant prostate cancer for 2 multiparametric magnetic resonance imaging risk calculators while the other calculators showed worse calibration at 11% to 27%. A clinical net benefit was observed only for 3 multiparametric magnetic resonance imaging risk calculators at biopsy thresholds of 15% or greater. None of the 6 investigated prostate cancer risk calculators demonstrated clinical usefulness against a biopsy all strategy at thresholds less than 15%.The performance of multiparametric magnetic resonance imaging prostate cancer risk calculators varies but they generally outperform multiparametric magnetic resonance imaging naïve prostate cancer risk calculators in regard to discrimination, calibration and clinical usefulness. External validation in other biopsy settings is highly encouraged.

Key Points Question Was a change in hospital funding policy for radical prostatectomy associated with changes in management of localized prostate cancer in the province of Ontario, Canada? Findings In this population-based interrupted time series study, which included 33 128 patients with incident localized prostate cancer and 17 159 patients treated with radical prostatectomy, no statistically significant association of the change in hospital funding policy with most outcomes was found. However, potential improvement in appropriate patient selection for prostate cancer surgery was observed. Meaning The implementation of a hospital funding policy change aimed at improving health care quality and value was not associated with management of localized prostate cancer., This population-based, interrupted time series study evaluates whether changes in hospital funding policy in Ontario, Canada, aimed at improving health care quality and value were associated with changes in the management of localized prostate cancer or the characteristics of patients receiving radical prostatectomy for localized prostate cancer., Importance Hospital funding reforms for prostate cancer surgery may have altered management of localized prostate cancer in the province of Ontario, Canada. Objective To determine whether changes in hospital funding policy aimed at improving health care quality and value were associated with changes in the management of localized prostate cancer or the characteristics of patients receiving radical prostatectomy (RP) for localized prostate cancer. Design, Setting, and Participants This population-based, interrupted time series study used linked population-based administrative data regarding adults in Ontario with incidental localized prostate cancer and those who underwent RP for localized prostate cancer. Patients who underwent RP were compared with patients who underwent surgical procedures for localized renal cell carcinoma, which was not included in the policy change but was subjected to similar secular trends and potential confounders. Monthly outcomes were analyzed using interventional autoregressive integrated moving average models. Data were collected from January 2011 to November 2017 and analyzed in January 2019. Exposures Funding policy change in April 2015 from flexible block funding for all hospital-based care to prespecified payment amounts per procedure for treatment of localized prostate cancer, coupled with the dissemination of a diagnosis-specific handbook outlining best practices. Main Outcomes and Measures Initial management (RP vs radiation therapy vs active surveillance) and tumor risk profiles per management strategy among incident cases of localized prostate cancer. Additional outcomes were case volume, mean length of stay, proportion of patients returning to hospital or emergency department within 30 days, proportion of patients older than 65 years, mean Charlson Comorbidity Index, and proportion of minimally invasive surgical procedures among patients undergoing RP for localized prostate cancer. Results A total of 33 128 patients with incident localized prostate cancer (median [interquartile range (IQR)] age, 67 [61-73] years; median [IQR] cases per monthly observation interval, 466 [420-516]), 17 159 patients who received radical prostatectomy (median [IQR] age, 63 [58-68] years; median [IQR] cases per monthly observation interval, 209 [183-225]), and 5762 individuals who underwent surgery for renal cell carcinoma (median [IQR] age, 62 [53-70] years; median [IQR] cases per monthly observation interval, 71 [61-77]) were identified. By the end of the observation period, radical prostatectomy and radiation therapy were used in comparable proportions (30.3% and 28.9%, respectively) and included only a small fraction of low-risk patients (6.4% and 2.9%, respectively). No statistically significant association of the funding policy change with most outcomes was found. Conclusions and Relevance The implementation of funding reform for hospitals offering RP was not associated with changes in the management of localized prostate cancer, although it may have encouraged more appropriate selection of patients for RP. Mostly preexisting trends toward guideline-conforming practice were observed. Co-occurring policy changes and/or guideline revisions may have weakened signals from the policy change.

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and 0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p

Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2–21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p

To evaluate the role of preoperative multiparametric magnetic resonance imaging (MRI) as predictor of post-prostatectomy incontinence (PPI). We analyzed patients who underwent robot-assisted radical prostatectomy for localized prostate cancer at our institution between July 2015 and April 2017. In these patients, we measured the perfusion quality of the pelvic floor with contrast media kinetics in the preoperative MRI of the prostate and compared the levator ani muscle (region of interest) to the surrounding pelvic muscle structures (reference). Prospectively collected questionnaires regarding urinary incontinence were then evaluated 1 year postoperatively. Outcomes were dichotomized into “continent” (ICIQ-Score = 0–5) and “incontinent” (ICIQ-Score ≥ 6). In each patient, we determined the perfusion ratio of the levator ani muscle divided by the surrounding pelvic muscle structures and compared them among the groups. Forty-two patients were included in the study (n = 22 in “continent”, n = 20 in “incontinent” group). The median perfusion ratio from the continent group was significantly higher compared to the incontinent group (1.61 vs. 1.15; 95% CI 0.09–0.81, p = 0.015). The median perfusion ratio in “excellent” (ICIQ-Score = 0) was significantly higher than in “poor” (ICIQ-Score ≥ 11) outcomes (1.48 vs. 0.94; 95% CI 0.04–1.03, p = 0.036). Further, a higher perfusion ratio was negatively correlated with ICIQ-Score (r = − 0.33; 95% CI − 0.58 to 0.03; p = 0.031). Our data demonstrate a promising new strategy to predict PPI through the perfusion quality of pelvic muscle structures with contrast media kinetics. This may facilitate preoperative patient consulting and decision-making.

INTRODUCTION AND OBJECTIVES:To minimize morbidity of surgery or radiation, active surveillance (AS) is standard of care in low-risk prostate cancer (PC). Predicting which men on AS will progress an...

INTRODUCTION AND OBJECTIVES:While radical prostatectomy (RP) renders good cancer control, urinary incontinence (UI) remains a major morbidity issue and significantly influences the postoperative qu...

INTRODUCTION AND OBJECTIVES:Photoselective vaporization of the prostate (PVP) with the so-called 532nm greenlight laser is an accepted treatment modality for non-neurogenic lower urinary tract symp...

ObjectivesTo systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy.Materials and methodsMEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB).ResultsThe literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59).ConclusionPooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.

Bipolar plasma vaporization (BPV) has been shown to be a low-morbidity alternative to conventional transurethral resection of the prostate (TURP). Improved functional short-term outcome and a postoperative prostate volume reduction comparable to TURP have been reported. However, comprehensive mid- or long-term results following BPV are still lacking.A consecutive series of men who underwent pure BPV in a tertiary care academic center was prospectively investigated. Clinical parameters [International Prostate Symptom Score with Quality-of-Life domain, peak urinary flow rate (Qmax), postvoid residual volume, and prostate-specific antigen] as well as prostate volume (assessed by planimetric volumetry following transrectal 3D-ultrasound) were recorded preoperatively and regularly after BPV (after catheter removal, 6 weeks, 6 months, 1 year, and 3 years). Statistical analysis was performed using the Wilcoxon signed-rank test. All p-values ≤0.05 were considered significant.Seventy-five men were included in this prospective investigation. Their median (interquartile range) prostate volume was 41.0 mL (30.6-57.4 mL). In the first year after BPV, the prostate volume continuously decreased over time and the relative volume reduction was 52.2% after 12 months. Subsequently, the volume reduction remained stable with 50.7% after 3 years. All investigated outcome parameters improved significantly after the procedure and remained so after 3 years. Reoperations due to persistent or regrown adenoma were not necessary. Six (8.0%) and five patients (6.6%) developed a de novo urethral stricture or bladder neck contracture, respectively.Three years after pure BPV of the prostate, a durable prostate volume reduction in combination with a stable improvement of functional outcome parameters was detectable in our prospective study. The low morbidity of the procedure and the possibility to perform BPV under ongoing platelet aggregation inhibition confirms its role as minimally invasive alternative to conventional TURP.

We externally validated a novel prostate cancer risk calculator based on data from the Swiss arm of the ERSPC and assessed whether the risk calculator (ProstateCheck) is superior to the PCPT-RC and SWOP-RC in an independent Swiss cohort.Data from all men who underwent prostate biopsy at an academic tertiary care center between 2004 and 2012 were retrospectively analyzed. The probability of having any prostate cancer or high grade prostate cancer (Gleason score 7 or greater) on prostate biopsy was calculated using the ProstateCheck. Risk calculator performance was assessed using calibration and discrimination, and additionally compared with the PCPT-RC and SWOP-RC by decision curve analyses.Of 1,615 men 401 (25%) were diagnosed with any prostate cancer and 196 (12%) with high grade prostate cancer. Our analyses of the ProstateCheck-RC revealed good calibration in the low risk range (0 to 0.4) and moderate overestimation in the higher risk range (0.4 to 1) for any and high grade prostate cancer. The AUC for the discrimination of any prostate cancer and high grade prostate cancer was 0.69 and 0.72, respectively, which was slightly but significantly higher compared to the PCPT-RC (0.66 and 0.69, respectively) and SWOP-RC (0.64 and 0.70, respectively). Decision analysis, taking into account the harms of transrectal ultrasound measurement of prostate volume, showed little benefit for ProstateCheck-RC, with properties inferior to those of the PCPT-RC and SWOP-RC.Our independent external evaluation revealed moderate performance of the ProstateCheck-RC. Its clinical benefit is limited, and inferior to that of the PCPT-RC and SWOP-RC.

To evaluate and compare postoperative changes in prostate volume and clinical outcome after bipolar plasma vaporization (BPV) and conventional transurethral resection of the prostate (TURP).Consecutive series of patients undergoing BPV or TURP were included in this prospective, nonrandomized study. Planimetric volumetry after transrectal three-dimensional ultrasound of the prostate was performed preoperatively and postoperatively after 6 weeks, 6 months and 12 months. Additionally, changes in clinical outcome parameters were assessed and compared between the groups. The reduction ratio and analysis of covariance were used to compare volume changes between BPV and TURP. Multiple regression analysis was performed to assess a possible interaction between preoperative prostate volume and effect of therapy.A total of 157 patients were included (BPV: n = 68, TURP: n = 89). Median preoperative prostate volume was 43.1 ml in the BPV group and 45.9 ml in the TURP group (p = 0.43). Postoperatively, the prostate volumes decreased significantly in both groups. After catheter removal, the relative residual prostate volume was significantly higher in the BPV group (66.6 vs. 60.8 %; p = 0.02). Thereafter, significant differences were not detectable anymore (12 months: 46.6 vs. 47.1 %; p = 0.82). Regression analysis revealed that tissue ablation after BPV was superior to TURP in prostates45 ml but inferior in prostates45 ml. All clinical outcome parameters improved significantly and were not significantly different between the groups.Volume reduction and short-term clinical outcome following pure BPV was excellent and comparable to conventional TURP. However, volume reduction seems to be limited in patients with larger prostates.

To assess whether and to what extent irrigation fluid absorption occurs during laser vaporization (LV) of the prostate using the 180 W XPS™ GreenLight laser. This prospective investigation was performed in a tertiary care center with a consecutive series of patients undergoing 180 W LV of the prostate. Intraoperative irrigation was performed with isotonic saline containing 1 % ethanol. The volume of irrigation fluid absorption was calculated from periodically performed breath ethanol measurements during LV. Additionally, intraoperative changes in biochemical and hematological blood parameters were assessed. Positive breath ethanol tests were detectable in 22 of 54 patients. The median absorption volume in these patients was 950 ml (range 208–4579 ml). Ten patients absorbed more than 2000 ml. Absorbers had smaller prostates, more capsular perforations and injuries to venous sinuses, and more total energy was applied with higher output power. Five patients had transient symptoms potentially related to fluid absorption. A significant drop in hemoglobin, hematocrit, venous pH and bicarbonate and an increase in chloride were detectable in the absorber group. These changes were significantly different in the non-absorber group. Absorption of irrigation fluid did occur in a relevant proportion of patients undergoing XPS™ GreenLight LV. High-volume absorption (≥2000 ml), which might be clinically relevant, was detectable in almost 20 % of all procedures. Absorption of saline irrigation fluid does not result in a classical TUR syndrome, but fluid and chloride overload can lead to serious complications, particularly in cardiovascular high-risk patients. Thus, patients with symptoms potentially related to fluid absorption should be monitored carefully.