Faculty Bibliography

PURPOSE:Recent evidence suggests that statins may improve prostate cancer outcomes; however, their role in active surveillance (AS) is poorly characterized. We aimed to evaluate the association between statin use at diagnosis and time to progression on AS. MATERIALS AND METHODS:Data were obtained from a prospectively maintained cohort of men undergoing AS between 1995 and 2016 at our institution. All men satisfied the low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen level <10.0 ng/dL. Kaplan-Meier curves and multivariable Cox proportional hazards were used to assess statin exposure at diagnosis and at time to pathological progression (failing to meet the low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of definitive therapy). Reclassification at confirmatory biopsy (first postdiagnostic biopsy) and progression beyond confirmatory biopsy were evaluated independently. RESULTS:Low-risk criteria were met by 797 men. Reclassification at the confirmatory biopsy occurred in 194 (24%) men, 51 (26%) of whom were statin users. Statin use was not associated with reclassification at confirmatory biopsy (odds ratio (OR): 1.24, 95% confidence interval (CI): 0.77-1.99). Among the remaining 603 men (median age: 63 years; follow-up: 60 months; 23% statin users), 149 (24%) had pathologic progression, while 200 (33%) had therapeutic progression. Statin exposure was not associated with pathological (multivariable hazard ratio (HR) 0.79, 95% CI: 0.51-1.23) or therapeutic (multivariable-HR 0.81, 95% CI: 0.55-1.19) progression beyond the confirmatory biopsy. Sensitivity analyses did not alter conclusions. CONCLUSIONS:In our study, statin use at diagnosis was not significantly protective against pathological or therapeutic progression in men undergoing AS for localized, low-risk prostate cancer.

BACKGROUND:Some centers offer assisted reproductive technologies (ARTs) [intra-uterine insemination (IUI) and in-vitro fertilization (IVF)], to treat certain couples with male factor infertility without having the men assessed by male infertility specialists. We sought to compare characteristics of couples having or not having prior ART use. METHODS:We used our prospectively collected database to identify men undergoing an initial evaluation for male infertility between 1995-2017. We obtained data on patient demographics, use of IUI and IVF, and semen analysis parameters. We used multivariable logistic regression to identify characteristics associated with prior use of ART. RESULTS:One thousand and five hundred forty-five out of 8,962 (17.2%) men reported use of ARTs prior to evaluation. Of these, 258 tried both IUI and IVF. More than one attempt was reported in 470 (37.2%) and 154 (28.2%) of men with prior IUI and IVF, respectively. Younger male age [adjusted odds ratio (aOR) 0.97/year; 95% confidence interval (CI), 0.95 to 0.99], older female partner age (aOR 1.07/year; 95% CI, 1.04 to 1.10), and year of visit (aOR 1.05/year; 95% CI, 1.01 to 1.09) were significantly associated with prior IUI. Older female partner age (aOR 1.07/year; 95% CI, 1.02 to 1.12) was significantly associated with prior IVF, but not male age or year of visit. Semen analysis parameters were not associated with prior ART. CONCLUSIONS:The prior use of ART is common among men presenting for an initial evaluation at a male infertility specialty clinic. Older female partner age was associated with use of reproductive technologies prior to evaluation, however, semen analysis parameters were not.

INTRODUCTION/BACKGROUND:Non-muscle-invasive bladder cancer (NMIBC) accounts for 75-85% of all urothelial bladder cancers (UBC). Many UBC patients are also afflicted by diabetes mellitus (DM). It has been postulated that several oral hypoglycemic agents could impact disease-specific survival (DSS), but the data are sparse among NMIBC patients. Our primary objective was to evaluate the impact of metformin on DSS and overall survival (OS) in NMIBC patients. METHODS:This is a retrospective, population-based study that used linked administrative databases to identify diabetic patients ≥66 years who were subsequently diagnosed with NMIBC in Ontario between 1992 and 2012. Cumulative use of metformin and other hypoglycemic agent were calculated before and after NMIBC diagnosis. DSS and OS were estimated using multivariable competing risk and Cox proportional hazards models, respectively. RESULTS:A total of 1742 subjects were included in the study. After a median followup of 5.2 years, 1122 (64%) had died, including 247 (15%) deaths as a result of UBC. On multivariable analysis, cumulative duration of metformin use after NMIBC diagnosis did not appear to impact DSS (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.92-1.2), whereas glyburide use appeared to have a detrimental effect (HR 1.17; 95% CI 1.02-1.3). None of the other hypoglycemic agents had an impact on OS. CONCLUSIONS:In this large, population-based study, we have provided further evidence that metformin use does not significantly impact DSS among diabetic patients diagnosed with NMIBC. However, our findings demonstrate that glyburide use inversely affects DSS. The detrimental effect of glyburide on DSS will require further validation.

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population-based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti-neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer-specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16-year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer-specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose-outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival.

Testicular cancer is the most common malignancy in young men, and the incidence is increasing in most countries worldwide. The vast majority of patients present with clinical stage I disease, and surveillance is being increasingly adopted as the preferred management strategy. At the time of diagnosis, patients on surveillance are often counselled about their risk of relapse based on risk factors present at diagnosis, but this risk estimate becomes less informative in patients that have survived a period of time without experiencing relapse. Conditional survival estimates, on the other hand, provide information on a patient's evolving risk of relapse over time. In this review, we describe the concept of conditional survival and its applications for surveillance of clinical stage I seminoma and nonseminoma germ cell tumours. These estimates can be used to tailor surveillance protocols based on future risk of relapse within risk subgroups of seminoma and nonseminoma, which may reduce the burden of follow-up for some patients, physicians, and the health care system. Furthermore, conditional survival estimates provide patients with a meaningful, evolving risk estimate and may be helpful to reassure patients and reduce potential anxiety of being on surveillance.

OBJECTIVES:To determine whether studies that used propensity score (PS) methods in the urology literature provide sufficient detail to allow scientific reproducibility and whether appropriate statistical tests were used to obtain valid measures of effect. MATERIALS AND METHODS:We searched OVID Medline and the Science Citation Index from inception to November 2016 to identify studies that used PS methods in five general urology journals. From each included article, we extracted pertinent information related to the PS methodology, such as estimation of the PS, whether balance diagnostics were performed, and the statistical analysis performed. RESULTS:We identified 114 articles for inclusion. Matching on the PS was the most common method used (62 studies, 54.4%). Of all studies, 103 (90.4%) described which covariates were used to estimate the PS; however, only 24 provided justification for the selected covariates. Although the majority of studies (70.2%) performed some sort of diagnostic evaluation to assess balance, few studies (24.6%) used appropriate methods for balance assessment. Only four (6.4%) studies that used PS matching provided sufficient detail to replicate the matching strategy. Finally, the majority (77.4%) of studies that used PS matching explicitly used inappropriate statistical methods to estimate the effect of an exposure on an outcome. CONCLUSIONS:In the urology literature PS methods were poorly described and implemented. We provide recommendations for improvement to allow scientific reproducibility and obtain valid measures of effect from their use.