Four-year quality-of-life outcomes in low- to intermediate-risk prostate cancer patients following definitive stereotactic body radiotherapy versus management with active surveillance.

OBJECTIVE: To review quality-of-life (QoL) metrics between patients who underwent definitive stereotactic body radiotherapy (SBRT) versus active surveillance (AS) for management of low- to intermediate-risk prostate cancer (PCa). METHODS: A prospectively maintained PCa database was reviewed containing results of patient-reported QoL surveys. Patients with localized disease who chose AS or SBRT and completed at least one survey within four years of treatment were included. Patients who received salvage therapy were excluded. Survey results were compared across time using mixed-effects repeated measures analysis of covariance models that adjusted for factors significant in univariate analysis. A group x time interaction effect was examined to compare rate of change over time between AS and SBRT. P < 0.05 was significant. RESULTS: 148 AS and 161 SBRT patients were included. Significantly more SBRT patients had intermediate-risk disease (p < 0.0001). AS had significantly worse sexual function compared to SBRT across time. While not significant, bowel function scores were lower for SBRT patients across time points. SBRT patients had significantly lower anxiety than AS patients at 24 months (p < 0.011) and 36 months (p < 0.010). Urinary function though worse in SBRT patients at 12 months in EPIC, was not significantly different in both groups across time points. CONCLUSION: SBRT patients have excellent QoL compared to AS with regard to anxiety post treatment. Though SBRT patients initially have worse urinary and bowel function than AS, scores were eventually similar in both cohorts by 48 months. SBRT patients have significantly worse sexual function post treatment. This study may help facilitate counseling in patients choosing PCa treatment.

The Natural History and Composition of Urinary Catheter Biofilms: Early Uropathogen Colonization with Intraluminal and Distal Predominance.

PURPOSE: We sought to determine the composition and initiation site of bacterial biofilm on indwelling urinary catheters and to track biofilm progression with time. MATERIALS AND METHODS: Indwelling urinary catheters were collected from 2 tertiary care centers following removal from patients. Indwelling time was noted and catheters were de-identified. Catheters were sectioned, stained for biofilms and analyzed by spectrophotometry and visualization. Biofilm colonization patterns were analyzed using descriptive statistical analysis and bacterial composition was determined using next generation sequencing. RESULTS: We collected and analyzed a total of 33 catheters from 26 males and 7 females with indwelling time ranging from 15 minutes to 43 days. Biofilm colonization was consistently high on the region of the balloon for all indwelling times. After week 1 the distal third of the catheter had higher biofilm colonization than the proximal third (week 2 p=0.034). At all indwelling times the intraluminal surface of the catheter had greater biofilm colonization than the outer surface. Next generation sequencing detected potential uropathogenic bacteria in all 10 analyzed samples. CONCLUSIONS: The catheter balloon, its distal aspect and its lumen were the predominant locations of biofilm comprising uropathogenic bacteria. Strategies to prevent or treat biofilm should be targeted to these areas.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

PURPOSE: We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. RESULTS: A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR. CONCLUSION: A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Salvage focal cryosurgery may delay use of androgen deprivation therapy in cryotherapy and radiation recurrent prostate cancer patients.

INTRODUCTION: Salvage treatment options for recurrent unilateral prostate cancer (PCa) after primary radiation are limited and associated with severe complications and poor quality of life measures. Salvage focal cryotherapy (SFC) has shown success in biochemical recurrence (BCR) free survival. We aim to determine if SFC can delay use of androgen deprivation therapy (ADT) in recurrent PCa with low morbidity. METHODS: A retrospective review of patients who underwent SFC at our institution from 2007 to 2015 was performed. Patients with <2 follow-up prostate-specific antigen (PSA) values, metastatic disease, and a history of radical prostatectomy were excluded. Age at treatment, prior treatment history, PSA nadir, complications, BCR status (nadir +2 ng/ml), and follow-up data were obtained/analysed. ADT was commenced if patient experienced BCR and had a PSA doubling time <6 months or positive confirmatory biopsy or positive imaging. Cox regression and survival analysis were used to assess confounding and time to BCR respectively. RESULTS: A total of 65 patients were included and followed for a median of 26.6 (8.0-99.0) months. Thirty-one (47.7%) patients did not experience BCR. An even higher number of patients (52/65, 80.0%) are yet to receive ADT. Of those who experienced BCR [median time to BCR, 17.1 [interquartile range (IQR):11.4-23.3] months], 22/34 (64.7%) are currently carefully monitored without ADT. Survival analysis showed a biochemical recurrence-free survival of 48.1 at 1- and 3-year follow up. No patient died/experienced major complications. CONCLUSIONS: SFC may be used to delay the use of ADT. Further assessment of our findings with high-powered studies and longer follow-up is required.

Temporal trends and factors associated with systemic therapy after cytoreductive nephrectomy: an analysis of the National Cancer Database.

PURPOSE: We evaluated temporal trends in systemic therapy use in patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma. We used data from a large national cancer registry and assessed characteristics associated with the receipt of systemic treatment. MATERIALS AND METHODS: We reviewed the NCDB to identify patients with stage IV renal cell carcinoma who underwent cytoreductive nephrectomy between 1998 and 2010. Systemic therapy was defined as immunotherapy and/or chemotherapy, including targeted agents. We evaluated associations between clinicopathological features and receipt of systemic therapy using multivariable logistic regression with generalized estimating equations. RESULTS: Of 22,409 patients with metastatic renal cell carcinoma treated with cytoreductive nephrectomy 8,830 (39%) received systemic therapy. Use of systemic therapy increased from 32% of cases in 1998 to 49% in 2010 (p < 0.001). After adjustment older patient age (71 years or greater OR 0.36, CI 0.31-0.43), increasing comorbidity count (Charlson comorbidity index 2 or greater OR 0.79, 95% CI 0.68-0.92), papillary histology (OR 0.81, 95% CI 0.71-0.93), sarcomatoid histology (OR 0.88, 95% CI 0.80-0.98), Medicaid (OR 0.61, 95% CI 0.5-0.74), Medicare (OR 0.70, 95% CI 0.62-0.79) and no insurance (OR 0.75, 95% CI 0.63-0.91) were associated with significantly decreased systemic therapy use. Male gender (OR 1.05, 95% CI 1.02-1.08) predicted an increased likelihood of systemic therapy. CONCLUSIONS: Systemic therapy in patients undergoing cytoreductive nephrectomy has increased with time, coinciding with the introduction of targeted therapies. Nevertheless, still less than half of such patients receive systemic treatment. While the etiology of the lack of treatment is likely multifactorial, the potential health policy implications of disparities in care warrant further investigation.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Coupling of prostate and thyroid cancer diagnoses in the United States.

BACKGROUND: Prostate and thyroid cancers represent two of the most overdiagnosed tumors in the US. Hypothesizing that patients diagnosed with one of these malignancies were more likely to be diagnosed with the other, we examined the coupling of diagnoses of prostate and thyroid cancer in a large US administrative dataset. METHODS: The surveillance, epidemiology, and end results (SEER) database was used to identify men diagnosed with clinically localized prostate cancer (CaP) or thyroid cancer between 1995 and 2010. SEER*stat software was used to estimate multivariable-adjusted standardized incidence ratios (SIRs) and investigate the rates of subsequent malignancy diagnosis. Additional non-urologic cancer sites were added as control groups. RESULTS: Patients with thyroid cancer were much more likely to be diagnosed with CaP than patients in the SEER control group (SIR 1.28 [95% CI 1.1-1.5]; p < 0.05). Similarly, the observed incidence of thyroid cancer was significantly higher in patients with CaP when compared with SEER controls (SIR 1.30 [95% CI 1.2-1.4]; p < 0.05). When stratified by follow-up interval, the observed thyroid cancer diagnosis rate among men with CaP was significantly higher than expected at 2-11 (SIR 1.83 [95% CI 1.4-2.4]), 12-59 (SIR 1.24 [95% CI 1.0-1.5]), and 60-119 (SIR 1.25 [95% CI 1.0-1.5]) months of follow-up. There was no increased risk of CaP or thyroid cancer diagnosis among patients with non-urologic malignancies. CONCLUSIONS: There is a significant association of diagnoses with prostate and thyroid cancer in the US. In the absence of a known biological link between these tumors, these data suggest that diagnosis patterns for prostate and thyroid malignancies are linked.

Variation in performance of candidate surgical quality measures for muscle-invasive bladder cancer by hospital type.

OBJECTIVE: To test the association between hospital type and performance of candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. PATIENTS AND METHODS: Using the National Cancer Database, patients with stage ≥II urothelial carcinoma treated with radical cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume (CLV), comprehensive high volume (CHV), academic low volume (ALV), and academic high volume (AHV) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. RESULTS: In all, 23 279 patients underwent RC at community (12.4%), comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0-2.9), ALV (OR 1.3, CI 1.1-1.6), and CHV (OR 1.3, CI 1.03-1.7) hospitals compared with community hospitals. CONCLUSIONS: Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC.

Hypoalbuminaemia is associated with mortality in patients undergoing cytoreductive nephrectomy.

OBJECTIVE: To evaluate whether poor nutrition is associated with mortality in patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A multi-institutional review of prospective databases identified 246 patients meeting inclusion criteria who underwent CN for mRCC from 1993 to 2012. Nutritional markers evaluated were: body mass index <18.5 kg/m(2) , serum albumin <3.5 g/dL, or preoperative weight loss of ≥5% of body weight. Primary outcomes were overall (OS) and disease-specific survival (DSS). Secondary outcome was 'early mortality' defined as death at ≤6 months of surgery. Survival curves were estimated using the Kaplan-Meier product-limit method and multivariate analysis using logistic regression was used to test associations between nutritional markers and survival outcomes. RESULTS: In all, 119 patients (median follow-up 17 months) were categorised as having any abnormal nutrition parameter (48%). Hypoalbuminaemia was the only independent predictor of OS and DSS (OS: median 8 vs 23 months, P < 0.001; DSS: 11 vs 33 months, P < 0.001). On multivariate analysis, hypoalbuminaemia remained a significant predictor of death for both overall [hazard ratio (HR) 2, 95% confidence interval (CI) 1.4-2.8; P < 0.001) and disease-specific mortality (HR 2.2, 95% CI 1.4-3.3; P < 0.001). Hypoalbuminaemia was also associated with early mortality (overall: P < 0.001 and disease specific: P = 0.002). CONCLUSION: Patients with mRCC and hypoalbuminaemia undergoing CN have decreased OS and CSS, and increased risk of all-cause and disease-specific early mortality. As such, serum albumin may help risk stratify patients selected as candidates for CN. Furthermore, future work should evaluate whether nutritional depletion is a modifiable risk factor.

Care transitions between hospitals are associated with treatment delay for patients with muscle invasive bladder cancer.

PURPOSE: Hypothesizing that changing hospitals between diagnosis and definitive therapy (care transition) may delay timely treatment, we identified the association between care transitions and a treatment delay of 3 months or greater in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: Using the National Cancer Database we identified all patients with stage II or greater urothelial carcinoma treated from 2003 to 2010. Care transition was defined as a change in hospital from diagnosis to definitive treatment course, that is diagnosis to radical cystectomy or the start of neoadjuvant chemotherapy. Logistic regression models were used to test the association between care transition and treatment delay. RESULTS: Of 22,251 patients 14.2% experienced a treatment delay of 3 months or greater and this proportion increased with time (13.5% in 2003 to 2006 vs 14.8% in 2007 to 2010, p = 0.01). Of patients who underwent a care transition 19.4% experienced a delay to definitive treatment compared to 10.7% diagnosed and treated at the same hospital (p <0.001). The proportion of patients with a care transition increased during the study period (37.4% in 2003 to 2006 vs 42.3% in 2007 to 2010, p <0.001). After adjustment patients were more likely to experience a treatment delay when undergoing a care transition (OR 2.0, 95% CI 1.8-2.2). CONCLUSIONS: Patients with muscle invasive bladder cancer who underwent a care transition were more likely to experience a treatment delay of 3 months or greater. Strategies to expedite care transitions at the time of hospital referral may improve quality of care.

Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy.

PURPOSE: Concern regarding coexisting malignant pathology in benign renal tumors deters renal biopsy and questions its validity. We examined the rates of coexisting malignant and high grade pathology in resected benign solid solitary renal tumors. MATERIALS AND METHODS: Using our prospectively maintained database we identified 1,829 patients with a solitary solid renal tumor who underwent surgical resection between 1994 and 2012. Lesions containing elements of renal oncocytoma, angiomyolipoma or another benign pathology formed the basis for this analysis. Patients with an oncocytic malignancy without classic oncocytoma and those with known hereditary syndromes were excluded from study. RESULTS: We identified 147 patients with pathologically proven elements of renal oncocytoma (96), angiomyolipoma (44) or another solid benign pathology (7). Median tumor size was 3.0 cm (IQR 2.2-4.5). As quantified by the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score, tumor anatomical complexity was low in 28% of cases, moderate in 56% and high in 16%. Only 4 patients (2.7%) were documented as having hybrid malignant pathology, all involving chromophobe renal cell carcinoma in the setting of renal oncocytoma. At a median followup of 44 months (IQR 33-55) no patient with a hybrid tumor experienced regional or metastatic progression. CONCLUSIONS: In our cohort of patients with a solitary, sporadic, solid benign renal mass fewer than 3% of tumors showed coexisting hybrid malignancy. Importantly, no patient harbored coexisting high grade pathology. These data suggest that uncertainty regarding hybrid malignant pathology coexisting with benign pathological components should not deter renal biopsy, especially in the elderly and comorbid populations.

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma.

OBJECTIVE: To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. RESULTS: Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64-0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63-1.26). CONCLUSIONS: Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Evaluation of a New Cystoscopic Cryocatheter and Method for the In Situ Destruction of Bladder Cancer: Preliminary In Vivo Study.

Purpose: To assess the ability to deliver full-thickness bladder wall cryoablation through a cystoscopic approach using a new closed-loop 6F cryocatheter and thermal dose-controlled protocol. Materials and Methods: Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice, and distal ureter). A 6F cryocatheter was passed through the working channel of a flexible cystoscope. Single 1- and 1.5-minute freeze protocols in a saline environment were evaluated and resultant lesion size was determined. A laparoscopic approach was utilized to observe the transmural extension of the ice propagation. Results: Studies demonstrated the generation of transmural lesions characterized by full-thickness histologic necrosis after freezing for 1.5 minutes regardless of tissue thickness (range 2-12 mm). All animals were found to have good overall health (maintained weight, appetite, mobility, and energy levels) throughout the recovery period. No significant deviations were noted in complete blood count and serum chemistry bloodwork except for elevated creatine kinase levels. Importantly, no fistulas or perforations were noted. Conclusions: The cryocatheter was able to rapidly and effectively freeze the bladder wall through a cystoscopic approach. The results showed the ability to consistently ablate an ∼1 cm diameter and up to 1.2 cm deep using a single 1.5-minute freeze protocol. Analysis of the ablation efficacy revealed ∼80% destruction within the frozen mass. Although further testing and refinement are needed, these studies demonstrate the potential of this new approach to provide a next-generation strategy for the treatment of bladder cancer.

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation.

Purpose: Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials: A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results: A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion: Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

Familiarity and self-reported compliance with American Urological Association best practice recommendations for use of thromboembolic prophylaxis among American Urological Association members.

PURPOSE: Thromboprophylaxis with subcutaneous heparin or low molecular weight heparin is now an integral part of national surgical quality and safety assessment efforts, and has been incorporated into the current AUA Best Practice Statement. We evaluated familiarity and compliance with the AUA Best Practice Statement, assessed practice patterns in terms of perioperative thromboprophylaxis and specifically examined self-reported compliance in high risk patients undergoing radical cystectomy. MATERIALS AND METHODS: An electronic survey was sent to AUA members with valid e-mail addresses (10,966). Associations between AUA Best Practice Statement adherence and factors such as urological specialty, graduation year and guideline familiarity were assessed using chi-square analyses and generalized estimating equations. RESULTS: With 1,210 survey responses the largest group of respondents was urological oncologists and/or laparoscopic/robotic specialists (26.0%). This group was more likely to use thromboprophylaxis than nonurological oncologists and/or laparoscopic/robotic specialists in high risk patients (OR 1.3, CI 1.1-1.5). Respondents aware of the AUA Best Practice Statement guidelines (50.7%) were more likely to use thromboprophylaxis (OR 1.4, CI 1.2-1.6). Although 18.1% of urological oncologists and/or laparoscopic/robotic specialists and 34.2% of nonurological oncologists and/or laparoscopic/robotic specialists avoided routine thromboprophylaxis in patients undergoing radical cystectomy, the former were more likely to use thromboprophylaxis (p <0.0001) than other respondents. Urologists graduating after the year 2000 used thromboprophylaxis in high risk patients undergoing radical cystectomy more often than did earlier graduates (79.2% vs 63.4%, p <0.0001). CONCLUSIONS: Although younger age and self-reported urological oncologist and/or laparoscopic/robotic specialist status correlated strongly with thromboprophylaxis use, self-reported adherence to AUA Best Practice Statement was low, even in high risk cases with clear AUA Best Practice Statement recommendations such as radical cystectomy. These data identify opportunities for quality improvement in patients undergoing major urological surgery.

Comparison of prostate cancer diagnosis in patients receiving unrelated urological and non-urological cancer care.

OBJECTIVE: To evaluate prostate cancer diagnosis rates and survival outcomes in patients receiving unrelated (non-prostate) urological care with those in patients receiving non-urological care. MATERIALS AND METHODS: We conducted a population-based study using the Surveillance Epidemiology and End Results (SEER) database to identify men who underwent surgical treatment of renal cell carcinoma (RCC; n = 18,188) and colorectal carcinoma (CRC; n = 45,093) between 1992 and 2008. Using SEER*stat software to estimate standardized incidence ratios (SIRs), we investigated rates of prostate cancer diagnosis in patients with RCC and patients with CRC. Adjusting for patient age, race and year of diagnosis on multivariate analysis, we used Cox and Fine and Gray proportional hazards regressions to evaluate overall and disease-specific survival endpoints. RESULTS: The observed incidence of prostate cancer was higher in both the patients with RCC and those with CRC: SIR = 1.36 (95% confidence interval [CI] 1.27-1.46) vs 1.06 (95% CI 1.02-1.11). Adjusted prostate cancer SIRs were 30% higher (P < 0.001) in patients with RCC. Overall (hazard ratio = 1.13, P < 0.001) and primary cancer-adjusted mortalities (sub-distribution Hazard Ratio (sHR) = 1.17, P < 0.001) were higher in patients with RCC with no significant difference in prostate cancer-specific mortality (sHR = 0.827, P = 0.391). CONCLUSION: Rates of prostate cancer diagnosis were higher in patients with RCC (a cohort with unrelated urological cancer care) than in those with CRC. Despite higher overall mortality in patients with RCC, prostate cancer-specific survival was similar in both groups. Opportunities may exist to better target prostate cancer screening in patients who receive non-prostate-related urological care. Furthermore, urologists should not feel obligated to perform prostate-specific antigen screening for all patients receiving non-prostate-related urological care.

Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens.

PURPOSE: This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients. METHODS: Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms. RESULTS: Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFß, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores. CONCLUSIONS: These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands.

PURPOSE: Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS: We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS: Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS: With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.

Comparative results of focal-cryoablation and stereotactic body radiotherapy in the treatment of unilateral, low-to-intermediate-risk prostate cancer.

OBJECTIVE: The purpose of this study is to compare oncologic and functional outcomes of men with unilateral, localized PCa treated with stereotactic body radiotherapy (SBRT) versus focal cryoablation (FC). METHODS: Patients from our IRB-approved PCa database who underwent FC or SBRT and were eligible for both treatments were included. Patients with less than 1 year of follow-up or prior PCa treatment were excluded. The primary outcome was treatment failure, defined as salvage treatment or a Gleason group (GG) of ≥ 2 on post-treatment biopsy. Biochemical recurrence (BCR) was evaluated with Phoenix. Functional outcomes were based on EPIC surveys. Complications were categorized with the CTCAE 5.0. Outcomes were compared using descriptive statistics, univariate analyses, and Kaplan-Meier curve for failure-free survival (FFS) and BCR-free survival. P < 0.05 was significant. RESULTS: 68 FC and 51 SBRT patients with a median age of 68 years (48-86) and a median follow-up time of 84 (70-101) months were included in this analysis. There was no difference in tumor risk (p = 0.47), GG (p = 0.20), or PSA (p = 0.70) among the two cohorts at baseline. At 7-year follow-up, no difference in FFS was found between the two cohorts (p = 0.70); however, significantly more FC patients had BCR (p < 0.001). At 48 months, no differences existed in urinary or bowel function; however, SBRT patients had significantly worse sexual function (p = 0.032). CONCLUSION: FC and SBRT are associated with similar oncologic and functional outcomes 7-year post-treatment. These results underscore the utility of FC and SBRT for the management of unilateral low-to-intermediate-risk PCa.