Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer.

BACKGROUND: Patients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC. OBJECTIVE: To investigate factors associated with the development of advanced CKD following radical cystectomy. DESIGN SETTING AND PARTICIPANTS: Using national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression. RESULTS AND LIMITATIONS: The median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10-1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29-1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00-1.41), higher comorbidity index (HR 1.13, 95% CI 1.11-1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73-0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort. CONCLUSIONS: Impaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy. PATIENT SUMMARY: Impaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

Twenty-four-hour Urine Testing and Urinary Stone Disease Recurrence in Veterans.

OBJECTIVE: To determine whether 24-hour urine testing in Veterans with USD (urinary stone disease) reduces or delays urinary stone recurrence. METHODS: Cohort study of national health record data from Veterans Health Administration from 2007 through 2013. We utilized a study population of 130,129 Veterans with USD based on diagnostic or procedural codes and excluded those with USD claims in the 2 years before cohort entry. We then created a propensity-score matched cohort of 14,854 Veterans based on completion of 24-hour urine testing within 6 months of stone diagnosis. Primary outcome was time-to-next clinically significant stone event, defined as an emergency department visit, inpatient admission related to a urinary stone, or urologic stone procedure with 5-year follow up. RESULTS: Of 14,854 Veterans in the propensity-score matched cohort, 8560 (57.6%) experienced a recurrent USD event. Completion of 24-hour urine testing was associated with a higher risk of developing a second stone event (hazard ratio [HR] 1.17, 95% confidence interval [95% CI] 1.12-1.22). Among Veterans with known recurrent disease, we examined time to a third stone event. In this cohort of 4736 patients, completion of 24-hour urine testing was not associated with a higher risk of developing a third stone event (HR 1.06, 95% CI 0.99-1.12). CONCLUSION: Completion of 24-hour urine testing was not associated with a reduction in urinary stone recurrence. These findings challenge the validity of a longstanding recommendation in general medicine, nephrology, and urology practice.

Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS).

BACKGROUND: Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous ("high-low") cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC. METHODS: We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test. RESULTS: The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24-1.48), leukocyte count (HR 1.40, 95%CI 1.30-1.51), platelet count (HR 1.36, 95%CI 1.27-1.51), and hemoglobin (HR 0.79, 95%CI 0.72-0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61-0.72), ferritin (HR 1.25, 95%CI 1.08-1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23-1.40), and C-reactive protein (HR 1.70, 95%CI 1.14-2.53). CONCLUSIONS: Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies.

Time Burden of Bladder Management in Individuals With Spinal Cord Injury.

BACKGROUND: While clean intermittent catheterization (CIC) is the gold standard for bladder management after spinal cord injury (SCI), many individuals with SCI, for reasons not fully understood, choose alternative bladder management. We hypothesized that CIC is associated with an increased time burden in individuals with SCI. OBJECTIVES: To investigate the time required to perform neurogenic bladder management in individuals with SCI. METHODS: An electronic nonvalidated questionnaire was designed to determine the self-reported time spent performing bladder management. It was sent to participants in the Neurogenic Bladder Research Group SCI Registry, a national quality of life study of individuals with SCI. RESULTS: Eighty-seven individuals responded to the survey. CIC was the most common bladder management (76%). Men and women performing independent CIC had similar average times with each catheterization episode (8.8 vs. 8.5 minutes, p = .864) as did women with a catheterizable stoma compared to women catheterizing per urethra (8.2 minutes, p = .913). Longer catheterization times were associated with cervical spine injury (mean 12.4 minutes per catheterization) and women requiring caregiver assistance (mean 20 minutes per catheterization). In addition, obese/overweight women had longer CIC times than normal weight women (14.5 minutes vs. 7 minutes; p = .036), while catheterization time was similar for all men regardless of body mass index. Individuals with indwelling catheters spent less than a third of the time on bladder management per day compared to those doing CIC (17 vs. 53 minutes per day, p < .001). CONCLUSION: Management of neurogenic bladder after SCI, especially in those performing CIC, is time consuming. This time burden may play a role in long-term bladder management decisions.

Deep learning enabled prediction of 5-year survival in pediatric genitourinary rhabdomyosarcoma.

BACKGROUND: Genitourinary rhabdomyosarcoma (GU-RMS) is a rare, pediatric malignancy originating from embryonic mesenchyme. Current approaches to prognostication rely upon conventional statistical methods such as Cox proportional hazards (CPH) models and have suboptimal predictive ability. Given the success of deep learning approaches in other specialties, we sought to develop and compare deep learning models with CPH models for the prediction of 5-year survival in pediatric GU-RMS patients. METHODS: Patients less than 20 years of age with GU-RMS were identified within the Surveillance, Epidemiology, and End Results (SEER) database (1998-2011). Deep neural networks (DNN) were trained and tested on an 80/20 split of the dataset in a 5-fold cross-validated fashion. Multivariable CPH models were developed in parallel. The primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Variables used for prediction were age, sex, race, primary site, histology, degree of tumor extension, tumor size, receipt of surgery, and receipt of radiation. Receiver operating characteristic curve analysis was conducted, and DNN models were tested for calibration. RESULTS: 277 patients were included. The area under the curve (AUC) for the DNN models was 0.93 for OS and 0.91 for DSS. AUC for the CPH models was 0.82 for OS and 0.84 for DSS. The DNN models were well-calibrated: OS model (slope = 1.02, intercept = -0.06) and DSS model (slope = 0.79, intercept = 0.21). CONCLUSIONS: A deep learning-based model demonstrated excellent performance, superior to that of CPH models, in the prediction of pediatric GU-RMS survival. Deep learning approaches may enable improved prognostication for patients with rare cancers.

Laboratory-wide association study of survival with prostate cancer.

BACKGROUND: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer. METHODS: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts. RESULTS: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort. CONCLUSIONS: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making. LAY SUMMARY: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones.

Importance: Approximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown. Objectives: To estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing. Design, Setting, and Participants: This cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020. Exposures: Elevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis. Main Outcomes and Measures: Proportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy. Results: The final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis. Conclusions and Relevance: This cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.

Contemporary multicenter outcomes of continent cutaneous ileocecocystoplasty in the adult population over a 10-year period: A Neurogenic Bladder Research Group study.

AIMS: Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study. METHODS: We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher's Exact tests were used to compare categorical variables. RESULTS: We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries. CONCLUSIONS: In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel.

The Urine Albumin-to-Creatinine Ratio and Kidney Function after Nephrectomy.

PURPOSE: Patients with kidney cancer are at risk for chronic kidney disease after radical and partial nephrectomy. We determined if the urine albumin-to-creatinine ratio is independently associated with progressive chronic kidney disease after nephrectomy. MATERIALS AND METHODS: We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with urine albumin-to-creatinine ratio measured in the 12 months before surgery. We fit multivariable models to determine if the urine albumin-to-creatinine ratio was associated with the time to chronic kidney disease progression (defined as reaching stage 4 or 5 chronic kidney disease, estimated glomerular filtration rate less than 30 ml/minute/1.73 m2). We performed a parallel analysis measuring the time to stage 3b, 4 or 5 chronic kidney disease (estimated glomerular filtration rate less than 45 ml/minute/1.73 m2) among patients with normal or near normal preoperative kidney function (estimated glomerular filtration rate 60 ml/minute/1.73 m2 or greater). We also examined the association between urine albumin-to-creatinine ratio and survival. RESULTS: A total of 1,930 patients underwent radical or partial nephrectomy and had preoperative urine albumin-to-creatinine ratio and preoperative and postoperative estimated glomerular filtration rate. Of these patients 658 (34%) and 157 (8%) had moderate (urine albumin-to-creatinine ratio 30 to 300 mg/gm) or severe albuminuria (urine albumin-to-creatinine ratio greater than 300 mg/gm), respectively. Albuminuria severity was independently associated with progressive chronic kidney disease after radical (moderate albuminuria HR 1.7, 95% CI 1.4-2.2; severe albuminuria HR 2.3, 95% CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95% CI 1.2-2.7; severe albuminuria HR 4.3, 95% CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy. CONCLUSIONS: In patients undergoing radical or partial nephrectomy the severity of albuminuria can stratify risk of progressive chronic kidney disease.

Quadruple immunotherapy of Bacillus Calmette-Guérin, interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor as salvage therapy for non-muscle-invasive bladder cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non-muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal. OBJECTIVE: We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s). METHODS: A retrospective review was performed. Patients received 6 treatments of quadruple immunotherapy (intravesical solution with one-third dose BCG, 50 million units IFN, and 22 million units interleukin-2, along with a 250-mcg subcutaneous sargramostim injection). Surveillance began 4 to 6 weeks after treatment completion. Patients received maintenance if recurrence-free. Success was defined as no recurrence (bladder or extravesical) and bladder preservation. Analysis was performed by Kaplan-Meier method (P<0.05). RESULTS: Fifty-two patients received treatment with a median recurrence follow-up of 16.3 months and overall follow-up of 41.8 months. All patients had at least 1 prior BCG failure and 13% had 2 or more prior failures. Only 3 patients (6%) were unable to tolerate full induction. Treatment success was 55% at 1 year, and 53% at 2 years. Thirteen patients (25%) underwent cystectomy at a median time of 17.3 months with disease progression to T2 in 1 patient and T3 in 2 patients. No patients had positive surgical margins or positive lymph nodes. CONCLUSIONS: In patients with non-muscle-invasive bladder cancer with prior BCG failure, quadruple immunotherapy demonstrated good treatment success in some patients and warrants further evaluation.

Experience with Sequential Intravesical Gemcitabine and Docetaxel as Salvage Therapy for Non-Muscle Invasive Bladder Cancer.

Patients with high-grade muscle invasive bladder cancer (NMIBC) receive intravesical therapy with bacillus Calmette-Guérin (BCG) as the well-established standard-of-care. However, even with prompt induction of intravesical therapy, approximately 40 % of patients will recur within 2 years. For patients who fail BCG, options include radical cystectomy, repeat BCG therapy, or alternative intravesical salvage therapy. In this review, we will discuss the most recent published evidence on salvage intravesical therapy with an emphasis on a more in-depth report of our therapeutic strategy with sequential gemcitabine and docetaxel intravesical therapy for this treatment-refractory population. In addition, we will provide practical advice on our approach to this challenging patient population including the use of operative staging to aid early identification of treatment failures.