Robotic Versus Open Cystectomy for Bladder Cancer: Synthesizing the Data from Current Systematic Reviews and Meta-Analyses.

This is a summary of existing systematic reviews comparing robotic assisted radical cystectomy (RARC) with open radical cystectomy (ORC). Our aim was to compare operative approaches with respect to perioperative, postoperative, oncologic, and health-related quality of life (QOL) outcomes. We performed a systematic review of MEDLINE, Medline-in-Process and Medline Epubs Ahead of Print, and the Cochrane Library on 22 February 2022. We included reviews of adult patients with bladder cancer undergoing RARC or ORC for muscle invasive or high-risk non-muscle invasive bladder cancer. Nonrandomized studies were excluded to minimize confounding and selection bias. The GRADE approach was used to determine the confidence in estimates. We assessed the quality of identified systematic reviews using AMSTAR 2 checklist. Six well-conducted, systematic reviews and meta-analyses were included. RARC was consistently associated with lower estimated blood loss (EBL) and transfusion rates, and longer operative time. There was inconsistent evidence for the impact of RARC on hospital length of stay (LOS). There was no significant difference in overall complication rate or major complication rate, or oncologic outcomes between groups. Comparison of QOL outcomes between studies was limited by statistical and methodological heterogeneity. RARC is associated with improvement in EBL and transfusion risk. There does not appear to be differences in oncologic outcomes or complications between approaches. Prospective studies are needed to assess the impact of diversion type, technique, and recovery pathways on patient outcomes and to assess the impact of operative approach on cost and patient-reported QOL.

The Importance of Repeat Imaging Prior to Treatment Decision-making in Testicular Cancer: Commentary From the Inaugural Global Society of Rare Genitourinary Tumors Summit.

Testicular cancer is a rare cancer that often affects young and otherwise healthy patients. Imaging plays a critical role in the staging and surveillance of patients with testicular cancer. Indeterminate findings on staging or surveillance imaging, can lead to challenging management decisions for clinicians and patients. In this article, we review the importance of short-interval, repeat imaging for several scenarios faced by patients with testicular cancer and their clinicians. The challenging scenarios and recommendations provided in this article summarize the discussion from the inaugural Global Society of Rare Genitourinary Tumors (GSRGT) Summit held on December 11-12, 2020.

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer: A Systematic Review and Meta-analysis.

Importance: Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. Objective: To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs). Data Sources: This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022. Study Selection: Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]). Data Extraction and Synthesis: Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Main Outcomes and Measures: Overall mortality and prostate cancer-specific mortality (PCSM). Results: Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes. Conclusions and Relevance: The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

The Effect of Age on Prostate Cancer Survival.

It is not clear to what extent the age of diagnosis and the attained age impact on cancer mortality rates in men with newly diagnosed prostate cancer. We estimated annual prostate cancer mortality rates and 20-year survival rates according to the age of diagnosis, race, grade and time since diagnosis using data from the Surveillance, Epidemiology and End-Results (SEER) program. We identified 116,796 prostate cancer patients diagnosed between 1992 and 1997 and followed them for 20 years. There were 21,896 deaths from prostate cancer. We calculated actuarial survival rates and annual prostate cancer mortality rates by age of diagnosis and by tumor grade. The risk of a man dying of prostate cancer was 17% for men diagnosed before age 70 and was 21% for those diagnosed after age 70. The mean annual prostate cancer mortality rate calculated over the 20-year period post-diagnosis was 1.5%. The annual rate increased from 0.9% for those diagnosed below age 60 to 2.1% for those diagnosed above age 70. For men with Gleason score ≥ 7 prostate cancer, the annual prostate cancer mortality rate peaked 2-3 years after diagnosis and then declined. For men diagnosed with Gleason score ≤ 6 prostate cancer, the annual prostate cancer mortality rate continued to rise 20 years after diagnosis and peaked after age 85. This suggests that high-grade prostate cancers are aggressive from the outset, but that low-grade prostate cancers may enter a state of dormancy and reactivate as the patient ages.

The role of prophylactic prostatectomy as a primary prevention strategy in high-risk germline mutation carriers.

PURPOSE OF REVIEW: Men with high-risk germline mutations are at significantly higher risk of developing and dying from prostate cancer. Current screening and treatment paradigms may lead to missed opportunities for cure. Herein we review the current literature on prevention, screening and treatment of these carriers and explore the potential role of prophylactic prostatectomy in primary prevention of prostate cancer mortality. RECENT FINDINGS: Prostate-specific antigen (PSA)-based screening has demonstrated marginal benefits in prostate cancer (PCa) survival and uncertainty remains on its true benefit among high-risk carriers. Recent results indicate that PCa in BRCA 2 carriers occurs at a higher incidence, younger age and progresses more rapidly compared with noncarriers. An intensified screening protocol of MRI and PSA in young carriers demonstrated how using PSA values alone may be insufficient. Current evidence indicates that high-risk carriers have worse survival outcomes after undergoing radical treatment for screening detected disease when compared with noncarriers. SUMMARY: Prophylactic prostatectomy within the context of a clinical trial is a reasonable primary prevention option for discussion with high-risk carriers, especially BRCA2 carriers during the shared decision-making process. Limitations exist in the current strategies of early PSA screening followed by radical treatment in this group.

An appraisal of genetic testing for prostate cancer susceptibility.

Most criteria for genetic testing for prostate cancer susceptibility require a prior diagnosis of prostate cancer, in particular cases with metastatic disease are selected. Advances in the field are expected to improve outcomes through tailored treatments for men with advanced prostate cancer with germline pathogenic variants, although these are not currently offered in the curative setting. A better understanding of the value of genetic testing for prostate cancer susceptibility in screening, for early detection and prevention is necessary. We review and summarize the literature describing germline pathogenic variants in genes associated with increased prostate cancer risk and aggressivity. Important questions include: what is our ability to screen for and prevent prostate cancer in a man with a germline pathogenic variant and how does knowledge of a germline pathogenic variant influence treatment of men with nonmetastatic disease, with hormone-resistant disease and with metastatic disease? The frequency of germline pathogenic variants in prostate cancer is well described, according to personal and family history of cancer and by stage and grade of disease. The role of these genes in aggressive prostate cancer is also discussed. It is timely to consider whether or not genetic testing should be offered to all men with prostate cancer. The goals of testing are to facilitate screening for early cancers in unaffected high-risk men and to prevent advanced disease in men with cancer.

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.

Focal therapy: definition and rationale.

PURPOSE OF REVIEW: The role of focal therapy for the treatment of prostate cancer is expanding in clinical practice. The aim of this review is to introduce readers to controversies in the use of focal therapy and its rationale. RECENT FINDINGS: There is a growing body of literature regarding the short-term and medium-term cancer control parameters and quality of life outcomes. These are mostly observational studies without a comparative arm. There is a need for high-quality randomize control trials comparing these treatments to definitive standard of care interventions (e.g. surgery or radiotherapy) in appropriate patient populations. SUMMARY: Focal therapy for prostate cancer has become an established therapeutic strategy. Evidence continues to accrue regarding its effectiveness. It is a useful treatment option for the appropriately selected patient, with the appeal of improved quality of life compared with standard therapies.

Management of stage I testicular cancer.

PURPOSE OF REVIEW: Testicular cancer is the most common solid malignancy amongst young men, and a large proportion present with stage I disease. The options for management following radical orchiectomy are multifold. We review here approaches to treatment in this setting, providing an update on recent publications. RECENT FINDINGS: At Princess Margaret Cancer Centre, we maintain a nonrisk adapted active surveillance approach. With a dedicated surveillance program using low-dose computed tomography imaging, patients are appropriately identified early for treatment on relapse. There are ongoing investigations into minimizing toxicities of treatments for relapse, and in particular, retroperitoneal lymph node dissection (RPLND) presents an attractive alternative. This, though, remains investigational in the setting of seminoma. SUMMARY: Testicular cancer is a highly curable malignancy. In stage I disease, an active surveillance approach following radical orchiectomy is preferred, irrespective of risk-profile. This approach serves to limit the toxicity of adjuvant treatment in a significant proportion of patients, while maintaining excellent survival outcomes.

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.

A Clinical Trial of Prophylactic Prostatectomy for BRCA2 Mutation Carriers: Is Now the Time?

The greater availability and use of genetic testing have improved our ability to determine that men with BRCA2 mutations are at significantly higher risk of developing and dying of prostate cancer. We should continue research efforts in secondary prevention for this population, but must also explore primary preventative strategies such as prophylactic prostatectomy. Efforts are under way at our institution for a clinical trial in this area.

Development, implementation, and evaluation of a competency-based didactic and simulation-focused boot camp for incoming urology residents: Report of the first three years.

INTRODUCTION: The Royal College of Physicians and Surgeons of Canada's Competence by Design (CBD) initiative presents curricula challenges to ensure residents gain proficiency while progressing through training. To prepare first-year urology residents (R1s), we developed, implemented, and evaluated a didactic and simulation-focused boot camp to implement the CBD curriculum. We report our experiences and findings of the first three years. METHODS: Urology residents from two Canadian universities participated in the two-day boot camp at the beginning of residency. Eleven didactic and six simulation sessions allowed for instruction and deliberate practice with feedback. Pre-and post-course multiple-choice questionnaires (MCQs) and an objective structured clinical exam (OSCE) evaluated knowledge and skills uptake. For initial program evaluation, three R2s served as historical controls in year 1. RESULTS: Nineteen residents completed boot camp. The mean age was 26.4 (±2.8) and 13 were male. Participants markedly improved on the pre- and post-MCQs (year 1: 62% and 91%; year 2: 55% and 89%; year 3: 58% and 86%, respectively). Participants scored marginally higher than the controls on four of the six OSCE stations. OSCE scores remained >88% over the three cohorts. All participants reported higher confidence levels post-boot camp and felt it was excellent preparation for residency. CONCLUSIONS: During its first three years, our urology boot camp has demonstrated high feasibility and utility. Knowledge and technical skills uptake were established via MCQ and OSCE results, with participants' scores near or above those of R2 controls. This boot camp will remain in our CBD curriculum and can provide a framework for other urology residency programs.

Long-term Testis Cancer Survivors in Canada-Mortality Risks in a Large Population-based Cohort.

BACKGROUND: Testis cancer (TC) patients are young with excellent cancer prognosis. Hence, the risk of late-onset treatment-related morbidity and mortality is of concern due to longer survival after treatment. OBJECTIVE: We set to characterize long-term survival of TC patients through a Canadian population dataset. DESIGN SETTING AND PARTICIPANTS: We used a population-based dataset, the Canadian Census Health and Environment Cohort (CanCHEC), to identify individuals diagnosed with TC between 1991 and 2010. We compared them with all other male individuals without TC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was mortality due to cardiovascular disease (CVD) or nontesticular malignancy. Mann-Whitney or chi-square test was used where applicable. Data were analyzed using a Cox proportional hazard model with and without matching. RESULTS AND LIMITATIONS: We identified 1950 individuals with TC. We compared them with 1 300 295 men with no TC. There were 335 deaths in the study group during the study period (17.2%) with a mean follow-up of 19.6 yr. TC patients were at increased risk of death from secondary malignancies (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.39-1.91; p < 0.0001) with specific risks for hematologic neoplasms (HR 3.86, 95% CI 2.78-5.37; p < 0.001) and other malignancies (HR 2.41, 95% CI 1.76-3.29; p < 0.001). Gastrointestinal, hematologic, and respiratory toxicities were the most common secondary malignancies leading to death. When stratified according to histology, nonseminoma (NS) patients were at significantly increased risk of death from CVD (HR 2.03, 95% CI 1.27-3.25; p = 0.0032). Individuals with seminoma were at increased risk of death from other nontestis neoplasms (HR 1.46, 95% CI 1.17-1.82; p = 0.0007), specifically hematologic neoplasms (HR 2.09, 95% CI 1.18-3.72; p = 0.0118). CONCLUSIONS: NS patients are at increased risk of CVD-related death, whereas seminoma patients are at increased risk of death from non-testis-related malignancies. PATIENT SUMMARY: We report long-term mortality following diagnosis of testis cancer. Nonseminoma patients have an increased risk of death from cardiovascular disease, while seminoma patients have an increased risk of death from secondary malignancies.

The ability of prior urinary cultures results to predict future culture results in neurogenic bladder patients.

AIMS: To determine if previous urinary cultures can predict the organism and susceptibility of subsequent urinary cultures in patients with neurogenic bladder dysfunction. METHODS: We retrospectively identified a sample of neurogenic bladder patients from a tertiary care urology clinic (July 2015-July 2016). We reviewed the patient chart, and then used the electronic laboratory record to identify all urine cultures done in the 2 years prior. We identified sequential culture pairs and determined the concordance of the initial culture organism to the subsequent one and similarly the concordance of the initial culture's antibiotic resistance status to the subsequent culture's one. RESULTS: We identified 146 people with neurogenic bladder (mostly due to spinal cord injury [n = 61], multiple sclerosis [n = 26], or spina bifida [n = 25]). These individuals used primarily intermittent catheterization (n = 69, 47%) spontaneous voiding (n = 59, 40%), or indwelling foley catheter (n = 31, 21%). During the previous 2-years, 81 participants had at least two positive urine cultures and a total of 479 cultures could be examined for organism/susceptibility concordance. There was 56% concordance of bacterial species between subsequent urine cultures, and this decreased significantly with increasing time between cultures (P = 0.02). Antibiotic susceptibility concordance was high for ciprofloxacin (77%), nitrofurantoin (79%), and trimethoprim-sulfamethoxazole (75%), with no significant change with increasing time between cultures (P > 0.90). CONCLUSIONS: Previous positive urine cultures can provide valuable information regarding future organism and antibiotic susceptibility in individuals with neurogenic bladder. The practise of reviewing the previous urine culture when selecting empiric therapy is likely an effective practise in this population.

The impact of patient-, disease-, and treatment-related factors on survival in patients with adrenocortical carcinoma.

INTRODUCTION: Adrenal cortical carcinoma (ACC) is a rare and aggressive endocrine tumour. Most present with advanced disease and have poor prognosis. Optimal treatment includes complete surgical resection. There is limited evidence for the efficacy of chemotherapy and radiation at different stages in this disease. There remain many inconsistencies with respect to diagnosis and workup. There is a lack of uniform guideline recommendations and consensus data. METHODS: We performed a retrospective chart review of all patients at London Health Sciences Centre between 1990 and 2015 using ICD coding. All paper and electronic charts were reviewed and data was collected. Statistical analysis and survival curves were performed. RESULTS: A total of 29 patients were included in our study. Median age was 55 years (interquartile range [IQR] 45-63); 14 (48%) were male and 15 (52%) were female. Approximately half (14 or 48%) of our patients presented symptomatically. Almost half (41%) of tumours were metabolically active, producing hormones. Most (88%) underwent surgical intervention. Surgical margin status was available in about half of patients and lymphadenectomy was performed in a third (n=8) of open adrenalectomy patients. A third received mitotane treatment (8 [73%] adjuvant and 3 [27%] palliative) and a third of patients received radiation. Two- and five-year median overall survival was 53% and 27%, respectively. CONCLUSIONS: ACC is a rare and aggressive tumour. This is the largest Canadian series reported to the best of our knowledge. Limited data for guidelines exists and treatment and workup patterns are inconsistent. Collaborative randomized and prospective studies on a global basis are needed.

A case control analysis investigating risk factors and outcomes for nephrocalcinosis and renal calculi in neonates.

INTRODUCTION: Studies on outcomes and risk factors for neonatal nephrocalcinosis (NC) and renal calculi (RC) are limited, and often do not include controls for comparison. We conducted a case-control analysis to identify risk factors associated with NC and/or RC in neonates and studied the natural course of these anomalies. STUDY DESIGN: Infants diagnosed with NC/RC on ultrasound within the first year of life and corresponding gestational age- and gender-matched controls were identified from the neonatal intensive care unit database at our institution over a 10-year period. Risk factors assessed included: low birth weight, small for gestational age, nephrotoxic drugs, respiratory support therapy, use of total parental nutrition (TPN), surgeries, history of UTIs, creatinine at presentation, and history of maternal hypertension. Unadjusted odds ratios were estimated. Chi square analysis was performed for binary variables and the Mann-Whitney U test for continuous variables. Outcomes examined include time to resolution of NC/RC, renal function, and hypertension. RESULTS: We identified 22 cases of NC/RC with corresponding matched controls. Median follow-up was 28 months (IQR 0-122 months). History of urinary tract infections (UTI) was the only variable significantly associated with the presence of NC/RC (OR 5.62, 95% CI 1.12-31.1, p < 0.013) (Table). All other known risk factors were comparable in both groups. There was no difference in the incidence of hypertension (OR 2.94, 95% CI 0.40-33.82, p = 0.216) at diagnosis or last follow-up between the groups. Resolution of NC/RC was observed in 72.7%, during a median follow-up of 12.1 months. Mean urinary calcium/creatinine ratio for the NC/RC group was 2.3 ± 1.5 at diagnosis and 0.96 ± 0.8 at last follow-up. DISCUSSION: Most NC/RC in infants resolve without surgical intervention but some infants require medical therapy and follow-up. Risk factors for NC/RC in neonates continue to be poorly defined because of the quality of studies available. Our study provides further adjustment for confounders but has a small sample size and is restricted to neonates from an intensive care unit. CONCLUSION: Most cases of NC/RC resolve spontaneously without surgical intervention. The mean time to resolution is 12.1 months, without untoward consequences in terms of hypertension. A history of UTIs is the only identified risk factor identified in this study which is associated with a significant increased risk of neonatal nephrocalcinosis and/or renal calculi. Larger prospective studies are warranted to confirm these findings.

Corticosteroid Usage Is Associated With Increased Artificial Urinary Sphincter Reoperation.

OBJECTIVE: To determine if oral corticosteroid use is associated with an increased risk of artificial urinary sphincter (AUS)-related reoperation. MATERIALS AND METHODS: Administrative data from Ontario were used to conduct a retrospective cohort study. Men >65 years of age who underwent implantation of an AUS between 2002 and 2013 were included. Prescriptions for oral corticosteroids were identified, and men were considered exposed from the date the prescription was dispensed to 180 days after the expected end of the prescription. The primary outcome was AUS reoperation. Data were analyzed using a Cox proportional hazards model with corticosteroid usage modeled as a time-varying covariate. RESULTS: We identified 747 men who met our inclusion criteria (median age of 71 years; interquartile range [IQR]: 68-75), of which 592 (79.3%) had a prior radical prostatectomy. The median duration of follow-up was 3.2 years (IQR: 1.3-5.9). One hundred seventy-five (23.4%) patients were exposed to corticosteroids during the study period (median duration of use was 21 days; IQR: 5-100). We identified an AUS reoperation in 176 men (23.6%). After adjusting for age, radiation exposure, and year of implantation, exposure to corticosteroids was significantly associated with the risk of AUS reoperation (hazard ratio: 1.68, 95% confidence interval: 1.03-2.75, P = .04). Radiation after AUS implantation was also significantly associated with AUS reoperation (hazard ratio: 2.07, 95% confidence interval: 1.06-4.07, P = .03). CONCLUSION: There is a significantly increased risk of AUS reoperation among men using oral corticosteroids.