Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Microhematuria: AUA/SUFU Guideline.

PURPOSE: Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy. MATERIALS AND METHODS: The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens. RESULTS: Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation. CONCLUSIONS: Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

Development and evaluation of a bladder Cancer specific survivorship care plan by patients and clinical care providers: a multi-methods approach.

BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.

American Urological Association Nonmuscle Invasive Bladder Cancer Risk Model Validation-Should Patient Age be Added to the Risk Model?

PURPOSE: We evaluated the AUA (American Urological Association)/SUO (Society of Urologic Oncology) nonmuscle invasive bladder cancer risk model to predict nonmuscle invasive bladder cancer recurrence and progression prior to death. MATERIALS AND METHODS: We performed a retrospective analysis using electronic medical records and cancer registry data of patients with nonmuscle invasive bladder cancer in a multicenter United States patient population. We evaluated recurrence-free and progression-free survival according to the AUA/SUO nonmuscle invasive bladder cancer risk model. We then assessed discriminative performance with the c-index and compared the cumulative incidence of recurrence, progression and death across 4 age groups. RESULTS: We identified 1,297 patients with nonmuscle invasive bladder cancer. Median followup in the cohort was 3.2 years. The c-index of the AUA/SUO recurrence model was 0.62 and for progression it was higher at 0.77. Patients younger than 60 years had a 40% greater probability of recurrent nonmuscle invasive bladder cancer vs death while patients 84 years old or older had a 12% greater probability of death prior to recurrence at 5 years. This study was limited by its retrospective design. CONCLUSIONS: The AUA/SUO nonmuscle invasive bladder cancer risk model provides predictive performance of recurrence and progression similar to that of previous similar risk models, such as the models of the European Organization for Research and Treatment of Cancer, the Club Urológico Español de Tratamiento Oncológico and the National Comprehensive Cancer Network®. This work illustrates the need to consider age in predictive tools for clinicians who treat patients with nonmuscle invasive bladder cancer.

The Impact of Agent Orange Exposure on Prostate Cancer Outcomes.

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.

Impact of bilateral biopsy-detected prostate cancer on an active surveillance population.

BACKGROUND: To assess factors that can predict active surveillance (AS) failure on serial transrectal ultrasound guided biopsies in patients with low-risk prostate cancer. METHODS: We evaluated the records of 144 consecutive patients enrolled in AS between 2007 and 2014 at a single academic institution. Low risk inclusion criteria included PSA < 10 ng/ml, cT1c or cT2a, Grade Group (GG) 1, < 3 positive cores, and < 50% tumor in a single core with the majority having a PSA density of < 0.15. AS reclassification was defined as progression to GG ≥2, 3 or more cores, or core tumor volume ≥ 50%. Univariate and multivariate Cox proportional hazards regression analysis was used to determine predictors of reclassification and a match-pair analysis performed on a control group of patients choosing surgery. RESULTS: Inclusion criteria were met by 130 men with a median follow-up of 52 months. The reclassification or AS failure rate was 38.5%, with the majority 41/50 (82%) finding GG ≥ 2 cancer. Most patients had unilateral disease on diagnostic biopsy (94.6%), but 40.7% had bilateral cancer detected during follow-up. Men with bilateral detected tumor were more likely to ultimately fail AS than patients with unilateral tumors (HR 4.089; P < 0.0001) and failed earlier with a reclassification-free survival of 32 vs 119 months respectively. In a matched-pair analysis using a population of 211 concurrent patients that chose radical prostatectomy rather than AS, 76% of patients with unilateral cancer on biopsy had bilateral cancer on final pathology. CONCLUSIONS: The finding of bilateral prostate cancer on biopsy is associated with earlier AS reclassification. Finding bilateral disease may not represent disease progression, but rather enhanced detection of more extensive disease highlighting the importance of confirmatory biopsy.

Metformin Use is Associated with Improved Survival for Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy.

PURPOSE: Metformin is commonly prescribed for patients with type 2 diabetes mellitus. We hypothesized that metformin plus androgen deprivation therapy may be beneficial in combination. Our objective was to assess this combination in a retrospective cohort of patients with advanced prostate cancer. MATERIALS AND METHODS: Using national Veterans Affairs databases we identified all men diagnosed with prostate cancer between 2000 and 2008 who were treated with androgen deprivation therapy with followup through May 2016. Study exclusions included treatment with androgen deprivation therapy for 6 months or longer, or receipt of androgen deprivation therapy concurrently with localized radiation. Three patient cohorts were developed, including no diabetes mellitus, diabetes mellitus with no metformin and diabetes mellitus with metformin. Cox proportional HRs were calculated for overall survival, skeletal related events and cancer specific survival. RESULTS: After exclusions the cohort consisted of 87,344 patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and no metformin, and 17% with diabetes mellitus on metformin. Cox proportional hazard analysis of overall survival showed improved survival in men with diabetes mellitus on metformin (HR 0.82, 95% CI 0.78-0.86) compared to those with diabetes mellitus who were not on metformin (HR 1.03, 95% CI 0.99-1.08). The reference group was men with no diabetes mellitus. Cox proportional hazard analysis of predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72-0.93) in men with diabetes mellitus on metformin. Cox proportional hazard analysis of cancer specific survival showed improved survival in men with diabetes mellitus on metformin (HR 0.70, 95% CI 0.64-0.77) vs those with diabetes mellitus without metformin (HR 0.93, 95% CI 0.85- 1.00). The reference group was men with no diabetes mellitus. CONCLUSIONS: Metformin use in veterans with prostate cancer who receive androgen deprivation therapy is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Predicting Nonmuscle Invasive Bladder Cancer Recurrence and Progression in a United States Population.

PURPOSE: We assessed the performance of the EORTC (European Organisation for Research and Treatment of Cancer) and CUETO (Club Urológico Español de Tratamiento Oncológico) nonmuscle invasive bladder cancer predictive models compared to current United States NCCN Guidelines® in an American population. MATERIALS AND METHODS: We retrospectively analyzed the electronic medical records of patients with nonmuscle invasive bladder cancer in a multicenter population in the United States. We evaluated recurrence-free and progression-free survival according to EORTC and CUETO, and assessed discriminative performance with the c-index at 1 and 5 years. We then compared the discrimination of EORTC and CUETO to the discrimination of the 4 nonmuscle invasive bladder cancer treatment groups described in NCCN Guidelines. RESULTS: We identified 1,333 patients with nonmuscle invasive bladder cancer and a median followup of 37 months. At 5 years the recurrence c-index of EORTC and CUETO was 0.59 and 0.56 while for progression it was higher at 0.74 and 0.72, respectively. NCCN Guidelines demonstrated a similar c-index of 0.56 and 0.75, respectively. The discrimination of all 3 risk models decreased in patients who received bacillus Calmette-Guérin. EORTC was better able to identify patients at low risk for recurrence or progression but it overestimated the 5-year risk of progression in patients at high risk. This study was limited by its retrospective design. CONCLUSIONS: Our work illustrates the need for improved predictive tools for clinicians who treat patients with nonmuscle invasive bladder cancer. However, until new tools are developed NCCN Guidelines are a simple option for clinicians who treat patients with nonmuscle invasive bladder cancer. Those guidelines provide predictive power comparable to that of the EORTC and CUETO models.

Tolerability of Repeat Use of Blue Light Cystoscopy with Hexaminolevulinate for Patients with Urothelial Cell Carcinoma.

PURPOSE: Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events. RESULTS: A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride. CONCLUSIONS: In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride.

Emerging Impact of Malnutrition on Surgical Patients: Literature Review and Potential Implications for Cystectomy in Bladder Cancer.

PURPOSE: Malnutrition is emerging as a significant factor in patient outcomes. A contemporary review of malnutrition has not been performed for the urologist. We review the available literature and current standards of care for malnutrition screening, assessment and intervention, focusing on patients with bladder cancer treated with cystectomy. MATERIALS AND METHODS: Our multidisciplinary team searched PubMed® for available literature on malnutrition, focusing on definition and significance, importance to urologists, screening, assessment, diagnosis, immunological and economic impacts, and interventions. RESULTS: The prevalence of malnutrition in hospitalized patients is estimated to range from 15% to 60%, reaching upward of 71% in those with cancer. Malnutrition has been shown to increase inflammatory markers, further intensifying catabolism and weight loss. Bladder cancer is catabolic and patients undergoing cystectomy have increased resting energy expenditure postoperatively. Data are emerging on the impact of malnutrition in the cystectomy population. Recent studies have identified poor nutritional status based on low albumin or sarcopenia (loss of muscle) as having an adverse impact on length of hospitalization, complications and survival. The current standard of care malnutrition assessment tool, the 2012 consensus statement of the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition, has not been evaluated in the urological literature. Perioperative immunonutrition in patients undergoing colorectal surgery has been associated with significant decreases in postoperative complications, and recent pilot work has identified the potential for immunonutrition to positively impact the cystectomy population. CONCLUSIONS: Malnutrition has a significant impact on surgical patients, including those with bladder cancer. There are emerging data in the urological literature regarding how best to identify and improve the nutritional status of patients undergoing cystectomy. Additional research is needed to identify malnutrition in these patients and interventions to improve surgical outcomes.

Reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

OBJECTIVE: To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. PATIENTS AND METHODS: A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). RESULTS: In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 27% for patients with an eGFR of <60 mL/min/1.73 m2 (P < 0.001). Multivariable analysis showed that an eGFR of <60 mL/min/1.73 m2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 71% for patients with an eGFR of <60 mL/min/1.73 m2 (P = 0.01). CONCLUSION: Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance.

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

Prostate Biopsy in Active Surveillance Protocols: Immediate Re-biopsy and Timing of Subsequent Biopsies.

PURPOSE OF REVIEW: This manuscript reviews contemporary literature regarding prostate cancer active surveillance (AS) protocols as well as other tools that may guide the management of biopsy frequency and assess the possibility of progression in low-risk prostate cancer. RECENT FINDINGS: There is no consensus regarding the timing of surveillance biopsies; however, an immediate repeat biopsy within 12 months of diagnosis for patients considering AS confirms patients who have favorable risk disease yet also identifies patients who were undersampled initially. Studies regarding multiparametric MRI, nomograms, and biomarkers show promise in risk stratifying and counseling patients during AS. Further studies are needed to determine if these supplemental tests can decrease the frequency of surveillance biopsies. An immediate re-biopsy can help to reduce the risk of missing clinically significant disease. Other clinical tools, including mpMRI, exist that can be used as an adjunct to counsel patients and guide a personalized discussion regarding the frequency of surveillance biopsies.

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer.

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. RESULTS: Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). CONCLUSIONS: Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial.

Multi-Quadrant Biopsy Technique Improves Diagnostic Ability in Large Heterogeneous Renal Masses.

PURPOSE: Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs a standard biopsy technique. MATERIALS AND METHODS: Clinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared. RESULTS: A total of 122 biopsies were performed for 117 tumors in 116 patients (46 using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10 cm (IQR 8-12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (p=0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs 2 of 8 (25.0%) (p=0.0062). CONCLUSIONS: The multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates.

The Future State of Race/Ethnicity in Urology: Urology Workforce Projection From 2021-2061.

OBJECTIVE: To project the proportion of the urology workforce that is from under-represented in medicine (URiM) groups between 2021-2061. METHODS: Demographic data were obtained from AUA Census and ACGME Data Resource Books. The number of graduating urology residents and proportion of URiM graduating residents were characterized with linear models. Stock and Flow models were used to project future population numbers and proportions of URiM practicing urologists, contingent on assumptions regarding trainee demographics, retirement trends, and growth in the field. RESULTS: Currently, there is an increase in the percentage of URiM graduates by 0.145% per year. If historical trends continue, URiM urologists will likely comprise 16.2% of urology residency graduates and 13.3% of the practicing urological workforce in 2061. These percentages would constitute an underrepresentation of URiM urologists relative to the projected 44.2% of the U.S. population who would identify as American Indian/Alaskan Native, Black/African American, Latinx/Hispanic and Native Hawaiian/Pacific Islander by 2060.1 An increase in the percentage of URiM graduates by 0.845% per year would result in 44.2% URiM urology residency graduates and 26.1% URiM practicing urologists by 2061. An interactive app was designed to allow for a range of assumptions to be explored and for future data to be incorporated. CONCLUSION: URiM physician representation within urology over the next 40years will remain disproportionately low compared to that of the projected share of people of color in the general U.S. POPULATION: In order to achieve the AUA's Diversity, Equity and Inclusion goals, a concerted effort to implement interventions to recruit, train, and retain a generation of racially diverse urologists appears necessary.