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Simple Summary: The growth of minimally invasive techniques for radical nephroureterectomy (RNU) has significantly changed the surgical treatment landscape of non-metastatic upper urinary tract urothelial carcinoma in recent decades. The aim of this study was to compare perioperative and oncologic outcomes between open, laparoscopic, and robotic RNU using a retrospective, multicenter, multinational database. Using 756 propensity-score-matched patients out of a total of 2434, we found a worse bladder recurrence-free survival in patients undergoing laparoscopic and robotic RNU compared with open RNU. Recurrence-free, cancer-specific, and overall survival were similar between the three surgical approaches. Laparoscopic and robotic RNU revealed a shorter hospital length of stay and fewer major postoperative complications compared to open RNU. Although minimally invasive RNU techniques are associated with improved perioperative outcomes, further studies are warranted to investigate the underlying factors responsible for the worse bladder recurrence-free survival of patients treated with these techniques. Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990–2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien–Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan–Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22–2.28, p = 0.001 and HR 1.73, 95%CI 1.22–2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta −1.1, 95% CI −2.2–0.02, p = 0.047 and beta −6.1, 95% CI −7.2–5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31–0.79, p = 0.003 and OR 0.27, 95% CI 0.16–0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Measuring the quality of care is important in health care to improve the treatment of patients. In this investigation, we sought to identify five indicators ("pentafecta") that reflect the quality of care of patients who have cancer of the upper urinary tract (kidney and/or ureter) and are treated with surgical removal of the affected kidney and ureter. Furthermore, we searched for conditions that can predict a failure to achieve these criteria during treatment. The five indicators that define the pentafecta are the complete removal of the tumor without residuals, the complete removal of the ureter and its bladder part, the absence of complications related to the blood, the absence of severe complications related to the surgery, and the absence of tumor recurrence 12 months after the surgery. Of the 1718 patients included, 844 (49%) achieved all pentafecta criteria. These patients had higher chances at 5 years after the surgery to be alive and not to die from any cause (A) or from cancer (B) compared to those who did not achieve the pentafecta criteria (A: 68.7 vs. 50.1% and B: 79.8 vs. 62.7%, respectively). There were no conditions related to the patient that were found to predict a failure to achieve the pentafecta. Using quality indicators such as the proposed pentafecta for the assessment of the treatment of cancer patients may help define prognosis and improve patient care. Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed. [ABSTRACT FROM AUTHOR]

Objective: To determine if there is an association between patient body habitus as measured by body mass index (BMI), body surface area (BSA), preoperative prostate volume, postoperative specimen weight, and open conversion with cystotomy or perineal urethrotomy (PU) during holmium laser enucleation of the prostate (HoLEP). We attempt to provide meaningful criteria to assist in preoperative patient counseling.Materials and Methods: Three hundred consecutive patients underwent HoLEP between August 3, 2018 and February 20, 2020 by a single surgeon. Patient metrics were recorded in a database including age, height, weight, preoperative prostate volume, postoperative specimen weight, catheter dependence, and transfusion requirement. Nine patients were identified who had cystotomy (8) or PU (1) performed during HoLEP secondary to inability to complete the procedure using standard endoscopic technique. Univariate and multivariate statistical analysis was performed.Result: Younger age, higher BMI, higher BSA, and higher estimated prostate volume were associated with increased risk of open conversion during HoLEP. No patient with a BMI under 30 required open conversion.Conclusion: Men with BMI >30 kg/m2 or preoperative prostate volume >125 mL should be counseled on the possibility of open conversion with cystotomy or PU. Although the overall risk of conversion is low (3%), the risk may be as high as 10% for patients in the highest quartile of BMI (>30.5 kg/m2) and BSA (>2.2m2). [ABSTRACT FROM AUTHOR]

Introduction: A large part of the developing world continues to lack access to surgical care. Urology remains one of the least represented surgical subspecialties in global health. To begin understanding the burden of urological illness in sub-Saharan Africa, we sought to characterize all patients presenting to a tertiary care hospital in Malawi with a urological diagnosis or related complaint in the past year. Methods: Retrospective review of the surgical clinic and surgical theater record books at Zomba Central Hospital (ZCH) was performed over a one-year time span. Patients presenting with urological diagnoses or undergoing a urological procedure under local or general anesthetic in the operating theater were identified and entered into a database. Results: We reviewed 440 clinical patients. The most common clinical presentations were for urinary retention (34.7%) and lower urinary tract symptoms (15.5%). A total of 182 surgical cases were reviewed. The most common diagnoses for surgical patients were urethral stricture disease (22%), bladder masses (17%), and benign prostatic hyperplasia (BPH) symptoms (14.8%). Urethral stricturerelated procedures, including direct visual internal urethrotomy and urethral dilatation, were the most common (14.2% and 7.7%, respectively). BPH-related procedures, including simple prostatectomy and transurethral resection of the prostate were the second most common (6.7% and 8.2%, respectively). Conclusions: Urethral stricture disease, BPH, and urinary retention represent the clinical diagnoses with the highest burden of visits. Despite these numbers, few definitive procedures are performed annually. Further focus on urological training in sub-Saharan Africa should focus on these conditions and their surgical management. [ABSTRACT FROM AUTHOR]

Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa).Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided.Results: Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001).Conclusions: Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa. [ABSTRACT FROM AUTHOR]

Progressive multifocal encephalopathy (PML) is a rare demyelinating disease that typically presents in immunodeficient patients. We report a case of a previously healthy 62-Year-Old woman who suffered from an unsteady gait, throbbing headaches, and progressive left-sided weakness and numbness. Stroke was initially suspected based on imaging and symptoms. A series of follow-up magnetic resonance images of the brain showed a right parietal lesion growing in size as the patient became unable to walk and experienced increasing lethargy and confusion. A biopsy of the lesion was positive for the John Cunningham virus (JCV). A diagnosis of PML was made and she was started on mefloquine. No improvement was seen on this treatment and her condition worsened. Although PML remains uncommon in immunocompetent individuals, it cannot be ruled out based on their immune status. Although the exact cause remains uncertain, underlying or transient states of immunosuppression may be responsible for reactivation of the JCV in these patients. [ABSTRACT FROM AUTHOR]

Background: There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed.Objective: We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure.Design, Setting, and Participants: A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients.Results and Limitations: Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study.Conclusions: EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance. [ABSTRACT FROM AUTHOR]

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient. [ABSTRACT FROM AUTHOR]

Objective: To perform a cost-effectiveness evaluation comparing the management options for mid-size (1-2cm) renal stones including percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and shockwave lithotripsy (SWL).Methods: A Markov model was created to compare cost-effectiveness of PCNL, mini-PCNL, RIRS, and SWL for 1-2cm lower pole (index patient 1) and PCNL, RIRS, and SWL for 1-2 cm non-lower pole (index patient 2) renal stones. A literature review provided stone free, complication, retreatment, secondary procedure rates, and quality adjusted life years (QALYs). Medicare costs were used. The incremental cost-effectiveness ratio (ICER) was compared with a willingness-to-pay(WTP) threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed.Results: At 3 years, costs for index patient 1 were $10,290(PCNL), $10,109(mini-PCNL), $5,930(RIRS), and $10,916(SWL). Mini-PCNL resulted in the highest QALYs(2.953) followed by PCNL(2.951), RIRS(2.946), and SWL(2.943). This translated to RIRS being most cost-effective followed by mini-PCNL(ICER $624,075/QALY) and PCNL(ICER $946,464/QALY). SWL was dominated with higher costs and lower effectiveness. For index patient 2, RIRS dominated both PCNL and SWL. For index patient 1: mini-PCNL and PCNL became cost effective if cost ≤$5,940 and ≤$5,390, respectively. SWL became cost-effective with SFR ≥75% or cost ≤$1,236. On probabilistic sensitivity analysis, the most cost-effective strategy was RIRS in 97%, mini-PCNL in 2%, PCNL in 1%, and SWL in 0% of simulations.Conclusion: For 1-2cm renal stones, RIRS is most cost-effective. However, mini and standard PCNL could become cost-effective at lower costs, particularly for lower pole stones. [ABSTRACT FROM AUTHOR]

Objective: To better understand the safety and diagnostic yield of percutaneous core-needle biopsy (PCNB) for upper tract urothelial carcinoma (UTUC).Methods: Of 444 patients undergoing radical nephroureterectomy (RNU) for UTUC between 2009 and 2017 at our institution, 42 who had PCNB prior to RNU were identified for analysis. Endpoints included safety, diagnostic yield, and concordance with RNU pathology. PCNB specimens were deemed histologically concordant with RNU specimens for cases when cytologic evaluation of biopsy specimen and corresponding pathologic evaluation of RNU specimen both made a histologic diagnosis of urothelial carcinoma.Results: Median tumor size was 3.8 cm (1.2-10.2 cm). All lesions arose from the pelvicalyceal system. CT-guidance was utilized in 52% (n = 22), and ultrasound-guidance in 48% (n = 20). Relative to RNU pathology, 95% of PCNBs demonstrated histologic concordance. Histologic grade was provided in 69% (n = 29) of PCNBs, with a 90% (n = 26) concordance with surgical pathology. Grades 1-2 and 3 complications occurred in 14.3% (n = 6) and 2.4% (n = 1), respectively. At a median follow-up of 28.2 months (range, 1.2-97.1 months) after biopsy, no cases of radiographic tract seeding were identified.Conclusion: In our cohort of 42 patients undergoing RNU for UTUC, PCNB appeared a safe diagnostic tool with high histologic yield and grade concordance. With greater than 2 years of follow-up, no cases of tract seeding were identified. [ABSTRACT FROM AUTHOR]

Background Renal tumor biopsy (RTB) for the characterization of small renal masses (SRMs) has not been widely adopted despite reported safety and accuracy. Without pretreatment biopsy, patients with benign tumors are frequently overtreated. Objective To assess the diagnostic rate of RTBs, to determine their concordance with surgical pathology, and to assess their impact on management. Design, setting, and participants This is a single-institution retrospective study of 529 patients with biopsied solid SRMs ≤4 cm in diameter. RTBs were performed to aid in clinical management. Outcome measurements and statistical analysis Diagnostic and concordance rates were presented using proportions. Factors that contributed to a diagnostic biopsy were identified using a multivariable logistic regression. Results and limitations The first biopsy was diagnostic in 90% ( n = 476) of cases. Of the nondiagnostic biopsies, 24 patients underwent a second biopsy of which 83% were diagnostic. When both were combined, RTBs yielded an overall diagnostic rate of 94%. Following RTB, treatment could have been avoided in at least 26% of cases because the lesion was benign. Tumor size and exophytic location were significantly associated with biopsy outcome. RTB histology and nuclear grade were highly concordant with final pathology (93% and 94%, respectively). Adverse events were low (8.5%) and were all self-limited with the exception of one. Although excellent concordance between RTB and final pathology was observed, only a subset of patients underwent surgery following biopsy. Thus it is possible that some patients were misdiagnosed. Conclusions RTB of SRMs provided a high rate of diagnostic accuracy, and more than a quarter were benign. Routine RTB for SRMs informs treatment decisions and diminishes unnecessary intervention. Our results support its systematic use and suggest that a change in clinical paradigm should be considered. Patient summary Renal tumor biopsy (RTB) for pretreatment identification of the pathology of small renal masses (SRMs) is safe and reliable and decreases unnecessary treatment. Routine RTB should be considered in all patients with an indeterminate SRM for which treatment is being considered. [ABSTRACT FROM AUTHOR]

Background: Highly sensitive and specific urinary biomarkers for the early detection of bladder cancer (BC) to improve the performance of urinary cytology are needed.Objective: To investigate the usefulness of methylation markers in voided urine to identify BC presence and grade.Design, Settings, and Participants: 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.Results and Limitations: 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 P < 0.05). In multivariable analysis, NID2, TWIST1, and age were independent predictors of BC (all P < 0.05). 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Limited data exists on possible approaches to improve sperm DNA fragmentation index (DFI) when no identifiable cause is found. The effect of short abstinence on sperm parameters has been extensively studied, but rarely reported on the effect on DFI in infertile men. In this study, we aimed to determine whether a second ejaculate provided after very short abstinence demonstrates lower DFI rates in infertile men., Methods: This prospective cohort study was conducted at Mount Sinai Hospital, Toronto, Canada, a tertiary university affiliated hospital. All men having DFI testing in addition to the standard semen analysis were identified via a prospectively collected database. Infertile men were instructed to provide two semen samples 3-4 hours apart (the first sample was given after 2-5 days of abstinence) to test the effect on DFI levels. Data analysis was performed for the comparison of the change in sperm parameters and DFI between samples and between men with DFI above and under 30%., Results: A total of 52 men provided double ejaculates 3-4 hours apart. In the entire group, DFI decreased from 38.9%±21.4% to 35.1%±21.6% in the second sample (P<0.001). Semen volume was lower on the second sample (2.3±1.4 vs . 1.5±0.9 mL, P<0.001), while the remaining parameters did not change. Forty out of 52 patients (76.9%) had improved DFI (average of 6.0±4.0 percentage points). Change in DFI varied with 22/52 (42.3%) and 7/52 (13.5%) of patients found to have decreases in DFI >5% and >10% in the second ejaculate, respectively. For men with DFI of 30-40%, 64% (7/11) of DFIs reduced to the under 30% range. First DFI value was the only parameter associated with DFI decrease to under 30% in multivariate models [odds ratio (OR), 0.62; 95% confidence interval (CI): 0.39-0.98; P=0.04]., Conclusions: This study identified significant improvements in DFI in infertile men providing a second sample after 3-4 hours. Controlled trials are needed to determine if reproductive outcomes are improved using a second ejaculate for infertile men with high initial sperm DFI values., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-216/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Purpose: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities., Materials and Methods: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis., Results: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01)., Conclusions: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa)., Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided., Results: Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001)., Conclusions: Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)