Faculty Bibliography

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.

INTRODUCTION/BACKGROUND:In 2014, the Canadian Task Force on Preventive Health Care (CTFPHC) recommended against routine prostate cancer screening with the prostate-specific antigen (PSA) blood test. We surveyed Canadian primary care physicians (PCPs) to understand their opinions and attitudes towards prostate cancer screening in 2016. METHODS:Twenty PCPs piloted the survey to assess its accessibility. We distributed a flyer to 19 633 PCPs as an insert in a large mailed package inviting them to attend a national meeting, and later promoted the survey at the meeting. Multinomial logistic regression models examined factors associated with agreement of key guideline statements and the overall benefit of PSA screening. RESULTS:A total of 1254 PCPs responded (rate of 6.4%); 54.7% of physicians aware of the CTFPHC recommendations report screening less often as a result. Overall, 55.6% of PCPs feel that the risks of PSA screening outweigh the benefits. On multivariable analysis, physicians who did not read the guidelines, did not have an academic appointment, or were in practice for over 20 years were significantly more likely to disagree with the statement that men 55-69 years old should not be screened for prostate cancer with PSA. CONCLUSIONS:Our national survey found that the prostate cancer screening practices of Canadian PCPs varies widely across physician demographic groups, with almost equal numbers for or against. This has significant ethical, medical, and legal implications. The poor response rate to highly incentivized survey request may suggest a reluctance or general apathy towards this subject because of the Task Force recommendations. Future efforts should provide physicians with objective guidance around PSA screening, incorporating input from all stakeholders, including PCPs, urologists, and patients.

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.

Importance:Despite 3 decades of study, there remains ongoing debate regarding whether vasectomy is associated with prostate cancer. Objective:To determine if vasectomy is associated with prostate cancer. Data Sources:The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched for studies indexed from database inception to March 21, 2017, without language restriction. Study Selection:Cohort, case-control, and cross-sectional studies reporting relative effect estimates for the association between vasectomy and prostate cancer were included. Data Extraction and Synthesis:Two investigators performed study selection independently. Data were pooled separately by study design type using random-effects models. The Newcastle-Ottawa Scale was used to assess risk of bias. Main Outcomes and Measures:The primary outcome was any diagnosis of prostate cancer. Secondary outcomes were high-grade, advanced, and fatal prostate cancer. Results:Fifty-three studies (16 cohort studies including 2 563 519 participants, 33 case-control studies including 44 536 participants, and 4 cross-sectional studies including 12 098 221 participants) were included. Of these, 7 cohort studies (44%), 26 case-control studies (79%), and all 4 cross-sectional studies were deemed to have a moderate to high risk of bias. Among studies deemed to have a low risk of bias, a weak association was found among cohort studies (7 studies; adjusted rate ratio, 1.05; 95% CI, 1.02-1.09; P < .001; I2 = 9%) and a similar but nonsignificant association was found among case-control studies (6 studies; adjusted odds ratio, 1.06; 95% CI, 0.88-1.29; P = .54; I2 = 37%). Effect estimates were further from the null when studies with a moderate to high risk of bias were included. Associations between vasectomy and high-grade prostate cancer (6 studies; adjusted rate ratio, 1.03; 95% CI, 0.89-1.21; P = .67; I2 = 55%), advanced prostate cancer (6 studies; adjusted rate ratio, 1.08; 95% CI, 0.98-1.20; P = .11; I2 = 18%), and fatal prostate cancer (5 studies; adjusted rate ratio, 1.02; 95% CI, 0.92-1.14; P = .68; I2 = 26%) were not significant (all cohort studies). Based on these data, a 0.6% (95% CI, 0.3%-1.2%) absolute increase in lifetime risk of prostate cancer associated with vasectomy and a population-attributable fraction of 0.5% (95% CI, 0.2%-0.9%) were calculated. Conclusions and Relevance:This review found no association between vasectomy and high-grade, advanced-stage, or fatal prostate cancer. There was a weak association between vasectomy and any prostate cancer that was closer to the null with increasingly robust study design. This association is unlikely to be causal and should not preclude the use of vasectomy as a long-term contraceptive option.

BACKGROUND:Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. METHODS:We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesised to modulate cancer risk was obtained using prescription claims data. We modelled exposure in four different fashions: (1) as continuous exposures using (a) fractional polynomials (which allow for a non-linear relationship between an exposure and outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures denoting (a) ≥3 years versus <3 years exposure; or (b) "ever" versus "never" exposure. We used conditional logistic regression to estimate the association of medication exposure on incident kidney cancer. RESULTS:The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis. When utilising fractional polynomials, increasing cumulative exposure to acetylsalicylic acid, selective serotonin reuptake inhibitors, and proton-pump inhibitors was associated with significantly reduced risk of kidney cancer, while increasing exposure to antihypertensive drugs was associated with significantly increased risk. CONCLUSIONS:Our study provides impetus to further explore the effect of commonly prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer.