Does traditional pharmacotherapy augment behavioral modification in the treatment of nocturia?

AIMS: To assess the efficacy of traditional first-line non-antidiuretic pharmacotherapy for nocturia in the real-world outpatient urology setting. METHODS: We retrospectively analyzed voiding diaries from adult men treated for lower urinary tract symptoms (LUTS) at an outpatient urology clinic to identify pairs of voiding diaries with ≥1 nocturnal void at baseline and a corresponding follow-up diary completed within 1 year. We compared the odds of nocturia improvement (decrease of ≥1 nocturnal void) in patients started on LUTS pharmacotherapy versus behavioral modification alone. RESULTS: Two hundred and thirteen diary pairs from 93 patients were included. Fifty-seven diary pairs were identified from patients prescribed at least one LUTS drug on the initial visit and 156 diary pairs were identified from patients receiving behavioral modification alone. All standard voiding diary parameters were assessed, and only maximum voided volume differed at baseline (240 ml [interquartile range: 200-330 ml] vs. 280 ml [200-400 ml] with and without pharmacotherapy, respectively, p = 0.04). The odds of nocturia improvement did not significantly differ between pharmacotherapy and behavioral modification treatment groups (crude odds ratio [OR]: 1.16 [95% confidence interval: 0.63-2.16], p = 0.63; maximum voided volume [MVV]-adjusted OR: 1.19 [0.63-2.22], p = 0.59). In contrast, improvement in 24-h urinary frequency was more likely with pharmacotherapy versus behavioral modification alone (crude OR: 2.36 [1.22-4.56], p = 0.01; MVV-adjusted OR: 2.05 [1.05-4.01], p = 0.04). Results were consistent on subgroup analyses restricted to first diary pairs from each patient. CONCLUSION: Despite improvement in 24-h voiding frequency, there was no evidence that adjunctive pharmacotherapy provided a benefit in the treatment of nocturia in men receiving behavioral counseling.

Determinants of neoadjuvant chemotherapy for urothelial muscle-invasive bladder cancer: Does location matter?

INTRODUCTION: Bladder cancer care has been increasingly concentrated in high-volume metropolitan medical centres (ie, "regionalisation" of care). We aimed to assess the potential role of geographic factors, including facility region and distance to treatment centre, as determinants of neoadjuvant chemotherapy (NAC) delivery in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) using nationally representative data from the United States. METHODS: We queried the National Cancer Database to identify patients with cT2-cT4a, N0M0 urothelial MIBC who underwent radical cystectomy (RC) from 2006 to 2015. Patients who received radiation therapy, single-agent chemotherapy, adjuvant chemotherapy or systemic therapies other than multi-agent chemotherapy were excluded. Multivariate logistic regression analysis was performed to identify independent predictors of receiving NAC. RESULTS: A total of 5986 patients met the criteria for inclusion, of whom 1788 (29.9%) received NAC and 4108 received RC alone. Younger age, increased Charlson-Deyo score, increased cT stage, increased annual income, increased distance from cancer treatment centre, treatment at an Academic Research Program or Integrated Network Cancer Program and a later year of diagnosis were independently predictive of NAC receipt. Older age, Medicare insurance and treatment in the East South Central or West South Central regions were independently associated with decreased odds of NAC receipt. CONCLUSIONS: Distance to treatment centre and United States geographic region were found to affect the likelihood of NAC receipt independently of other established predictors of success in this quality-of-care metric. Access to transportation and related resources merits consideration as additional pertinent social determinants of health in bladder cancer care.

Well-being and education of urology residents during the COVID-19 pandemic: Results of an American National Survey.

BACKGROUND: The rapid spread of COVID-19 has placed tremendous strain on the American healthcare system. Few prior studies have evaluated the well-being of or changes to training for American resident physicians during the COVID-19 pandemic. We aim to study predictors of trainee well-being and changes to clinical practice using an anonymous survey of American urology residents. METHODS: An anonymous, voluntary, 47-question survey was sent to all ACGME-accredited urology programmes in the United States. We executed a cross-sectional analysis evaluating risk factors of perception of anxiety and depression both at work and home and educational outcomes. Multiple linear regressions models were used to estimate beta coefficients and 95% confidence intervals. RESULTS: Among ~1800 urology residents in the USA, 356 (20%) responded. Among these respondents, 24 had missing data leaving a sample size of 332. Important risk factors of mental health outcomes included perception of access to PPE, local COVID-19 severity and perception of susceptible household members. Risk factors for declination of redeployment included current redeployment, having children and concerns regarding ability to reach case minimums. Risk factors for concern of achieving operative autonomy included cancellation of elective cases and higher level of training. CONCLUSIONS: Several potential actions, which could be taken by urology residency programme directors and hospital administration, may optimise urology resident well-being, morale, and education. These include advocating for adequate access to PPE, providing support at both the residency programme and institutional levels, instituting telehealth education programmes, and fostering a sense of shared responsibility of COVID-19 patients.

Conservative Management Following Complete Clinical Response to Neoadjuvant Chemotherapy of Muscle Invasive Bladder Cancer: Contemporary Outcomes of a Multi-Institutional Cohort Study.

PURPOSE: We report the outcomes in patients with muscle invasive bladder cancer from 2 institutions who experienced a clinically complete response to neoadjuvant platinum based chemotherapy and elected active surveillance. It was unknown whether conservative treatment could be safely implemented in these patients. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with muscle invasive bladder cancer at our institutions who elected surveillance following a clinically complete response to transurethral resection of bladder tumors and neoadjuvant chemotherapy from 2001 to 2017. A clinically complete response was defined as absent tumor on post-chemotherapy transurethral resection of bladder tumor, negative cytology and normal cross-sectional imaging. RESULTS: In the 148 patients followed a median of 55 months (range 5 to 145) the 5-year disease specific, overall, cystectomy-free and recurrence-free survival rates were 90%, 86%, 76% and 64%, respectively. Of the patients 71 (48%) experienced recurrence in the bladder, including 16 (11%) with muscle invasive disease and 55 (37%) with noninvasive disease. Salvage radical cystectomy prevented cancer specific death in 9 of 12 patients (75%) who underwent cystectomy after muscle invasive relapse and in 13 of 14 (93%) after noninvasive relapse. CONCLUSIONS: We observed high rates of overall and disease specific survival with bladder preservation in patients who achieved a clinically complete response to neoadjuvant chemotherapy. These outcomes support the safety of active surveillance in carefully selected, closely monitored patients with muscle invasive bladder cancer. Future studies should aim to improve patient selection by identifying biomarkers predicting invasive relapse and developing novel imaging methods of early detection.

Primary Small Cell Carcinoma of the Kidney: Disease Characteristics and Treatment Outcomes.

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan-Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% ≥60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60-69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28-10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management.

Determinants of adequate lymph node dissection following neoadjuvant chemotherapy in patients with urothelial muscle-invasive bladder cancer: results from the National Cancer Database.

PURPOSE: Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymph node dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. METHODS: We queried the National Cancer Database to identify patients from 2006-2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). RESULTS: A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119-3.599], p < 0.001). The likelihood of adequate PLND was significantly decreased in patients of older age (0.607 [0.441-0.835], p = 0.002 for age 70-79 years; 0.459 [0.245-0.860], p = 0.015 for age ≥ 80 years), a Charlson-Deyo score of 1 (0.722 [0.537-0.971], p = 0.031), and those who were uninsured (0.530 [0.292-0.964], p = 0.038). CONCLUSIONS: Established predictors of PLND may not necessarily be generalizable to all patients undergoing treatment for bladder cancer. The interplay between PLND and NAC merits further study, particularly in view of recent literature calling into question the survival benefit of PLND in patients pre-treated with NAC.

Overnight Urge Perception in Nocturia Is Independent of Depression, PTSD, or Anxiety in a Male Veterans Administration Population.

STUDY OBJECTIVES: The goal of this study was to compare the urge perception associated with nocturnal voiding at the time of voiding in individuals with and without depression, posttraumatic stress disorder (PTSD), or anxiety diagnoses to test the hypothesis that patients with such diagnoses are more likely to experience insomnia-driven convenience voiding during the sleep period. METHODS: A database of voiding diaries with urge perception grades (UPGs) from 429 adult males seeking treatment for nocturia at a Veterans Affairs-based urology clinic was analyzed. The UPG categorizes perception for urinating from 0 (out of convenience) to 4 (desperate urge). Diaries completed by males age 18 years and older showing ≥ 2 nocturnal voids were included. Those included (n = 178) were divided into two cohorts based on the presence (n = 62) or absence (n = 116) of one or more previously established mental health diagnoses (depression, PTSD, or anxiety). The chi-square test was used to determine significance between groups. RESULTS: Patients with a mental health diagnosis were more likely to report convenience voiding compared to those without depression, PTSD, or anxiety (14.5% versus 0.8%, P < .01). However, most voids in both groups were associated with the perception of urinary urgency. There were no differences in urinary volumes or hourly rates of urine production between the groups. CONCLUSIONS: A relatively small subset of urology patients experience nocturnal voiding because they are awake for reasons other than the urge to void. Mental health factors had a substantial, albeit minimal, effect. Most nocturia reflects urgency to urinate rather than voiding by convenience.

Timing and Predictors of Early Urologic and Infectious Complications After Renal Transplant: An Analysis of a New York Statewide Database.

OBJECTIVES: The most common complications after renal transplant are urologic and are a cause of significant morbidity in a vulnerable population. We sought to characterize the timing and predictors of urologic complications after renal transplant using a statewide database. MATERIALS AND METHODS: We queried the New York Statewide Planning and Research Cooperative System database to identify patients who underwent renal transplant from 2005 to 2013. Postoperative complications included hydronephrosis, ureteral stricture, vesicoureteral reflux, nephrolithiasis, and urinary tract infections. Cox proportional hazards model was used to assess independent predictors of urologic complications. RESULTS: In total, 9038 patients were included in the analyses. Urologic complications occurred in 11.3% of patients and included hydronephrosis (12.0%), nephrolithiasis (2.8%), ureteral stricture (2.4%), and vesicoureteral reflux (1.5%). We found that 23% experienced at least one urinary tract infection. On multivariate analysis, predictors of urologic complications included medicare insurance, hypertension, and prior urinary tract infection. Graft recipients from living donors were less likely to experience urologic complications than deceased-donor kidney recipients (P < .001). CONCLUSIONS: Urologic complications occur in a significant proportion of renal transplants. Further study is needed to identify risk factors for complications after renal transplantation to decrease morbidity in this vulnerable population.

Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer.

BACKGROUND: Bladder-sparing treatment of muscle invasive bladder cancer (MIBC) with systemic chemotherapy plus transurethral resection of bladder tumors (TURBT) is increasingly seen in the literature -both in case series and subanalyses of patients who opt out of or are unfit for radical cystectomy (RC). Survival outcomes among these patients are often impressive, but these are typically small retrospective studies from single institutions and therefore of limited clinical value. OBJECTIVES: Our aim is to summarize the literature regarding definitive treatment of MIBC with systemic chemotherapy plus TURBT and provide a meta-analysis of survival outcomes for patients who received this treatment. METHODS: A systematic literature search was performed consistent with the Prisma statement to identify publications reporting the outcomes of patients treated with TURBT and systemic chemotherapy as definitive treatment for locally confined MIBC. Identified studies were screened in a two-stage process: first by title and abstract; then by full-text reading. 18 publications (518 patients) were included in the qualitative systematic review and 10 publications (266 patients) were included in the meta-analysis. The primary objective was overall survival (OS). RESULTS: Overall survival ranged from 20% to 87.5% across studies at median follow-up ranging 4 to 120 months. 5-year survival rate for all patients included in the meta-analysis was estimated to be 72% [95% CI: 64%, 82%]. CONCLUSIONS: Definitive treatment with systemic chemotherapy plus TURBT can lead to favorable survival outcomes in select patients. Further study to improve patient selection for this method of treatment is needed.

Long-term Survival Outcomes With Intravesical Nanoparticle Albumin-bound Paclitaxel for Recurrent Non-muscle-invasive Bladder Cancer After Previous Bacillus Calmette-Guérin Therapy.

OBJECTIVE: To report long-term follow-up results of a phase II trial of salvage intravesical nanoparticle albumin-bound (nab)-paclitaxel for patients with recurrent non-muscle-invasive bladder cancer after previous intravesical bacillus Calmette-Guérin (BCG) therapy. METHODS: This was a phase II trial investigating the use of intravesical nab-paclitaxel in patients with recurrent Tis, Ta, and T1 urothelial carcinoma who failed at least 1 prior induction course of intravesical BCG. Patients received 500 mg/100 mL of nab-paclitaxel in 6 weekly intravesical instillations. Complete responders were offered full-dose maintenance for 6 months. Overall survival, recurrence-free survival, cystectomy-free survival, and cancer-specific survival were assessed via Kaplan-Meier analysis. RESULTS: A total of 28 patients were enrolled with a median follow-up of 41 months (range 5-76). There were 22 men and 6 women with a median age of 79 (range 36-93), and the median number of prior intravesical therapies was 2. Twenty-one of the 28 patients (75%) were BCG refractory. Ten of the 28 patients (36%) achieved complete response. Six of the 28 patients remain cancer free, with a recurrence-free survival rate of 18%. Five-year overall and cancer-specific survival rates were 56% and 91%, respectively. Radical cystectomy occurred in 11 of the 28 patients (39%), of whom 2 out of 11 (18%) had pT2 or greater disease. CONCLUSION: With a median follow-up of 41 months, 18% of this cohort treated with nab-paclitaxel was disease free. Cystectomy-free survival was 61% and bladder cancer-specific mortality was 9%. Nab-paclitaxel is a reasonable treatment option in this high-risk population.

Collecting duct carcinoma of the kidney: Disease characteristics and treatment outcomes from the National Cancer Database.

OBJECTIVE: To use a large population-level database to assess survival outcomes for collecting duct renal cell carcinoma (CDRCC). MATERIALS AND METHODS: The National Cancer Database was queried for all cases of CDRCC and clear cell renal cell carcinoma (CCRCC) from 2004 to 2013. After removing patients with other cancer diagnoses, the analytic cohort was composed of 201,686 CCRCC and 577 CDRCC cases. Kaplan-Meier and cox proportional hazards analysis were employed to model survival. RESULTS: Compared to CCRCC, patients with CDRCC presented with higher grade and stage, node positive, and metastatic disease (70.7% vs. 30.0% with metastasis; P<0.001). Overall median survival for CDRCC was 13.2 months (95% CI: 11.0-15.5) compared to the 122.5 months (95% CI: 121.0-123.9) for CCRCC. On multivariate analysis of the CDRCC cohort, increasing T stage, high-grade disease, and metastasis were predictors of mortality. Of 184 patients with metastatic CDRCC, 113 underwent cytoreductive nephrectomy (CNx) whereas the rest were treated with chemo/radiation or observed. Survival outcomes were improved in patients who received both CNx with chemo/radiation compared to CNx alone (hazard ratio = 0.51, 95% CI: 0.32-0.79) or chemo/radiation alone (hazard ratio = 0.57, 95% CI: 0.37-0.89) on multivariate analysis. CONCLUSION: CDRCC is an aggressive subtype of renal cell carcinoma. Median survival is 13 months after diagnosis, drastically lower than for CCRCC. More than 70% of patients have metastatic disease at diagnosis. Chemo/radiation in addition to CNx is associated with a survival benefit over single mode therapy.

Predictors of biochemical recurrence after primary focal cryosurgery (hemiablation) for localized prostate cancer: A multi-institutional analytic comparison of Phoenix and Stuttgart criteria.

BACKGROUND: The Phoenix definition (PD) and Stuttgart definition (SD) designed to determine biochemical recurrence (BCR) in patients with postradiotherapy and high-intensity focused ultrasound organ-confined prostate cancer are being applied to follow patients after cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC). MATERIALS AND METHODS: We performed a retrospective review of patients who underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients were followed up with serial prostate-specific antigen (PSA). PSA levels, pre- and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA nadir+2ng/ml]; SD = [PSA nadir+1.2ng/ml]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox regression and survival analyses were performed to assess time to BCR using PD and SD. RESULTS: A total of 163 patients were included with a median follow-up of 36.6 (interquartile range: 18.9-56.4) months. In all, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariable Cox regression, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR = 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and 66.7% of those with BCR by the SD were found to have a Gleason score ≥7. CONCLUSION: Both the PD and the SD may be used to determine BCR in post-PFC patients. However, the ideal definition of BCR after PFC remains to be elucidated.