Christopher B. Allard

Defining a new testosterone threshold for medical castration: Results from a prospective cohort series

BACKGROUND We seek to determine if testosterone levels below the accepted castration threshold (50 ng/dL) have an impact on time to progression to castrate-resistant prostate cancer (CRPC). METHODS This is a prospective cohort series of patients undergoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone agonist or antagonist at a tertiary centre from 2006 to 2011. Serum testosterone level was assessed every 3 months. Patients with any testosterone >50 ng/dL were excluded. Patients were stratified into groups based on those achieving mean testosterone levels <20 ng/dL and <32 ng/dL. Progression to CRPC was assessed with the Kaplan-Meier method and compared with the log-rank test. RESULTS A total of 32 patients were included in this study. Mean patient follow-up was 25.7 months. Patients with a 9-month serum testosterone <32 ng/dL had a significantly increased time to CRPC compared to patients with testosterone 32 to 50 ng/dL (p = 0.001, median progression-free survival (PFS) 33.1 months [<32 ng/dL] vs. 12.5 months [>32 ng/dL]). Patients with first year mean testosterone <32 ng/dL also had a significantly increased time to CRPC compared to 32 to 50 ng/dL (p = 0.05, median PFS 33.1 months [<32 ng/dL] vs. 12.5 months [32-50 ng/dL]). A testosterone <20 ng/dL compared to 20 to 50 ng/dL did not significantly predict with time to CRPC. CONCLUSION This study supports a lower testosterone threshold to define optimal medical castration (T <32 ng/dL) than the previously accepted standard of 50 ng/dL. Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen.

The Effect of Resident Involvement on Perioperative Outcomes in Transurethral Urologic Surgeries

OBJECTIVE To conduct the first study of intra- and postoperative outcomes related to intraoperative resident involvement in transurethral resection procedures for benign prostatic hyperplasia and bladder cancer in a large, multi-institutional database. DESIGN Relying on the American College of Surgeons National Surgical Quality Improvement Program Participant User Files (2005-2012), we abstracted all cases of endoscopic prostate surgery (EPS) for benign prostatic hyperplasia and transurethral resection of bladder tumors (TURBTs). Multivariable logistic regression models were constructed to assess the effect of trainee involvement (postgraduate year [PGY] 1-2: junior, PGY 3-4: senior, PGY ≥ 5: chief or fellow) vs attending only on operative time and length of hospital stay, as well as 30-day complication, reoperation, and readmission rates. RESULTS In all, 5093 EPS and 3059 TURBTs for a total of 8152 transurethral resection procedures were performed during the study period for which data on resident involvement were available. In multivariable analyses, resident involvement in EPS or TURBT was associated with increased odds of prolonged operative times and hospital readmissions in 30 days independent of resident level of training. Resident involvement was not associated with overall complications or reoperation rates. CONCLUSIONS Resident involvement in lower urinary tract surgeries is associated with increased readmissions. Strategies to optimize resident teaching of these common urologic procedures in order to minimize possible risks to patients should be explored.

The impact of method of distal ureter management during radical nephroureterectomy on tumour recurrence.

INTRODUCTON Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multi-institutional Canadian radical nephroureterectomy database. METHODS We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed. RESULTS A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease. CONCLUSION Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.

Trends in utilisation, perioperative outcomes, and costs of nephroureterectomies in the management of upper tract urothelial carcinoma: a 10-year population-based analysis.

To perform a population‐based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high‐volume surgeons and it is unclear if the same favourable results occur at a national level.

Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States.

BACKGROUND Targeted therapies (TTs) have revolutionized metastatic renal cell carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL-2 use for mRCC in the TT era. METHODS Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient, disease, and hospital characteristics stratified by era (pre-TT uptake: 2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability. RESULTS An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles. CONCLUSIONS HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response.

Primary genitourinary melanoma: Epidemiology and disease-specific survival in a large population-based cohort

BACKGROUND Primary genitourinary (GU) melanoma is a rare disease, which is poorly characterized. OBJECTIVE To examine clinical characteristics and survival outcomes of primary GU melanoma among men and women. DESIGN, SETTING, AND PARTICIPANTS Retrospective study using the Surveillance, Epidemiology, and End Results database (1973-2010) was used to identify primary GU melanoma cases by tumor site and histology codes. We examined associations of GU melanoma with demographic, clinical, and pathologic characteristics, as well as disease-specific survival (DSS). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS DSS was calculated using the Kaplan-Meier method. Cox-proportional hazard models were used to calculate hazard ratios and 95% CI for factors associated with worse DSS. RESULTS AND LIMITATIONS A total of 1,586 histologically confirmed cases of primary GU melanoma were identified with a median age of 66.1 years (IQR: 55-80). Incidence of primary GU melanoma was 0.2cases/million among men and 1.80cases/million among women. Overall, 60.1% of patients had localized disease at presentation and 90.5% of patients had cancer-directed surgery. Patients with urothelial melanoma had the worst 5- and 10-year DSS (39% and 29%, respectively). Women with vulvar/vaginal melanoma had worse 5- and 10-year DSS compared to men with penile/scrotal melanoma. In multivariate analysis, decreased survival was associated with increasing age, distant stage, and lymph node involvement. Results are limited by the lack of standardized staging for primary GU melanoma and the retrospective design of our study. CONCLUSIONS Patients with primary GU melanoma present with advanced stage and have a poor prognosis. Women have worse DSS compared to men. DSS is negatively associated with advanced age at diagnosis, higher stage, and lymph node involvement. PATIENT SUMMARY Clinicians and patients must be aware of the poor disease-specific outcomes associated with primary GU melanoma. Most importantly, women fare worse than men and mucosal melanomas have worse outcomes compared to cutaneous melanomas.

The impact of Medicare eligibility on cancer screening behaviors

INTRODUCTION Lack of health insurance limits access to preventive services, including cancer screening. We examined the effects of Medicare eligibility on the appropriate use of cancer screening services in the United States. METHODS We performed a cross-sectional analysis of the 2012 Behavioral Risk Factor and Surveillance System (analyzed in 2014). Univariable and logistic regression analyses were performed for participants aged 60-64 and 66-70 to examine the effects of Medicare eligibility on prevalence of self-reported screening for colorectal, breast, and prostate cancers. Sub-analyses were performed among low-income (<

A novel endoscopic treatment for ureteric remnant hemorrhage post laparoscopic radical nephrectomy.

25,000 annual/household) individuals. RESULTS Medicare-eligible individuals were significantly more likely to undergo all examined preventive services (colorectal cancer OR: 1.90; 95% CI 1.79-2.04; prostate cancer OR: 1.29; 95% CI 1.17-1.43; breast cancer OR: 1.23; 95% CI 1.10-1.37) and the effect was most pronounced among low-income individuals (colorectal cancer OR: 2.04; 95% CI 1.8-2.32; prostate cancer OR: 1.39; 95% CI 1.12-1.72; breast cancer OR: 1.42, 95% CI 1.20-1.67). Access to a healthcare provider was the strongest independent predictor of undergoing appropriate screening, ranging from OR 2.73 (95% CI 2.20-3.39) for colorectal cancer screening in the low-income population to OR 4.79 (95% CI 3.95-5.81) for breast cancer screening in the overall cohort. The difference in screening prevalence was most pronounced when comparing Medicare-eligible participants to uninsured Medicare-ineligible participants (+33.2%). CONCLUSIONS Medicare eligibility impacts the prevalence of cancer screening, likely as a result of increased access to primary care. Low-income individuals benefit most from Medicare eligibility. Expanded public insurance coverage to these individuals may improve access to preventive services.

Data on Medicare eligibility and cancer screening utilization

Abstract Laparoscopic radical nephrectomy is commonly used to treat renal masses. Given the ubiquitous presence of this technique, rare complications are becoming more commonplace. It is thus essential that practicing urologists be aware of all possible complications as well as the novel management approaches that exist. This report presents a situation in which a patient developed rapid-onset, postoperative gross hematuria. This complication is rare and multiple sources of bleeding must be considered. In the situation reported here, the ureteric remnant was the cause of the unremitting gross hematuria. While others have described surgical exploration as the primary treatment, the authors were successful in using a minimally invasive endoscopic approach with fulguration and instillation of a fibrin sealant. Indeed, they propose that the endoscopic approach described herein may be considered first line in cases of unremitting gross hematuria originating from the ureteric remnant.

Canadian guidelines for postoperative surveillance of upper urinary tract urothelial carcinoma

Health insurance is associated with increased utilization of cancer screening services. Data on breast, prostate and colorectal cancer screening were abstracted from the 2012 Behavioral Risk Factor and Surveillance System. This data in brief includes two sets of analyses: (i) the use of cancer screening in individuals within the low-income bracket and (ii) determinants for each of the three approaches to colorectal cancer screening (fecal occult blood test, colonoscopy and sigmoidoscopy+fecal occult blood test). Covariates included education attainment, residency, and access to health care provider. The data supplement our original research article on the effect of Medicare eligibility on cancer screening utilization “The impact of Medicare eligibility on cancer screening behaviors” [1].