Faculty Bibliography

Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes.

PURPOSE:Studies evaluating the association between statin use and survival outcomes in renal cell carcinoma have demonstrated conflicting results. Our objective was to evaluate this association in a large clinical cohort by using propensity score methods to reduce confounding from measured covariates. METHODS:We performed a retrospective review of 893 patients undergoing nephrectomy for unilateral, M0 renal cell carcinoma between 2000 and 2014 at a tertiary academic center. Inverse probability of treatment weights were derived from a propensity score model based on clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between statin use and disease-free survival, cancer-specific survival, and overall survival in the sample weighted by the inverse probability of treatment weights. A secondary analysis was performed matching statin users 1:1 to statin nonusers on the propensity score. RESULTS:Of the 893 patients, 259 (29%) were on statins at the time of surgery. Median follow-up was 47 months (interquartile range: 20-80). Statin use was not significantly associated with disease-free survival (hazard ratio [HR] = 1.09, 95% CI: 0.65-1.81), cancer-specific survival (HR = 0.90, 95% CI: 0.40-2.01), or overall survival (HR = 0.89, 95% CI: 0.55-1.44). Similar results were observed when using propensity score matching. CONCLUSIONS:The present study found no significant association between statin use and kidney cancer outcomes. Population-based studies are needed to further evaluate the role of statins in kidney cancer therapy.

BACKGROUND:Previous studies have demonstrated that elevated neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios (PLRs) are associated with the presence of various malignancies. The present study evaluated various hematologic parameters and their association with renal tumor biopsy pathology. MATERIALS AND METHODS/METHODS:The clinical, hematologic, and pathologic parameters were obtained through a retrospective review of 475 diagnostic biopsy specimens of small renal masses from January 2001 to December 2013. The complete blood counts closest to and before the biopsies were obtained. The biopsy pathologic findings were divided into 3 groups: benign, primary renal malignancy, and nonrenal malignancy. The hematologic parameters were compared among the 3 groups. Receiver operating characteristic curves were constructed for the parameters that were significantly different among the groups. Multiple logistic regression models were used to assess whether the clinical and hematologic parameters were associated with benign or malignant pathologic findings. RESULTS:Hematologic parameters were available for 462 cases (97%). Pathologic examination of the biopsy specimens demonstrated benign, primary renal malignancy, and nonrenal malignancy in 114 (25%), 337 (73%), and 11 (2%) patients, respectively. The PLR was significantly (P = .010) different among the 3 groups and was significantly (P = .013) greater in those with nonrenal malignancies than in those with primary renal malignancies. Using a cutoff for the PLR of 202.9 gave a sensitivity of 63.6% and specificity of 82.2% for detecting a nonrenal malignancy. CONCLUSION/CONCLUSIONS:The hematologic parameters did not differ significantly between benign and primary renal malignant masses undergoing biopsy. The PLR might be useful as a simple and inexpensive marker to help distinguish nonrenal malignancies in the workup of a small renal mass.

INTRODUCTION/BACKGROUND:Institutional experience has been associated with improved outcomes for various malignancies, including testicular cancer. The present study evaluated whether institution at orchiectomy was associated with outcomes on active surveillance (AS) for clinical stage (CS) I germ cell tumours (GCT). METHODS:815 patients with CSI GCT managed with AS at the Princess Margaret Cancer Centre were identified. Princess Margaret is a tertiary academic institution with a multidisciplinary testicular cancer clinic involving radiation oncologists, medical oncologists, and urologists, and has research experience in testicular cancer care. The association between institution of orchiectomy (Princess Margaret vs. Other) and time to progression on AS was analyzed using multivariable Cox proportional hazards models. Academic vs. non-academic institutions were compared in a sensitivity analysis. RESULTS:Patients undergoing orchiectomy at Princess Margaret for non-seminoma GCT were significantly less likely to have pure embryonal carcinoma (EC) in orchiectomy pathology (odds ratio [OR] 0.33; p=0.008) and CSIB disease (OR 0.47; p=0.014). Seminoma characteristics did not differ significantly between institution groups. In non-seminoma GCT, median followup was 5.4 years, 27% progressed on AS, and institution of orchiectomy was not associated with time to progression in either univariate (hazard ratio [HR] 0.79; p=0.33) or multivariable analyses (HR 1.01; p=0.97). In seminoma, median followup was 4.7 years, 12% progressed on AS, and institution of orchiectomy was not associated with progression (univariate: HR 0.87; p=0.73; multivariable: HR 0.98; p=0.96). Sensitivity analyses demonstrated similar results. CONCLUSIONS:Among CSI GCT patients managed on AS at a specialized cancer centre, there appears to be no difference in oncologic outcomes based upon the institution where orchiectomy was performed.

BACKGROUND:Randomized controlled trials (RCT) provide the strongest evidence to justify interventions in patients. However, trials with inadequate methods are associated with bias and exaggerated treatment effects. A search of the literature was conducted to review RCTs in testicular cancer (TC) to assess demographic and trial reporting quality patterns over time. METHODS:MEDLINE and CENTRAL were queried for TC RCTs from 1989 to 2014. Demographic information was abstracted and reporting quality score was evaluated using the Consolidated Standards of Reporting Trials criteria. Linear regression was used to assess the trend in reporting quality over time. RESULTS:A total of 39 RCTs were identified, of which 25 were published from 1989 to 2001 and 14 were published from 2002 to 2014. Most (59%) of the RCTs involved chemotherapy as the intervention, had a medical oncologist as the first author (87%), and took place in Europe (59%). RCTs published between 2002 and 2014 had longer enrollment periods (mean = 6.1 [2.7] vs. 3.7 [1.5] years, P = 0.007), whereas the number of patients randomized, median follow-up, or time from manuscript submission to acceptance were not significantly different between the periods. For each increasing year of publication, there was a significant improvement of 1.34% points (95% CI: 0.86-1.83, P<0.0001) in the Consolidated Standards of Reporting Trials score. CONCLUSIONS:Fewer RCTs in TC were published in the recent 13-year period. Although the quality of trial reporting improved compared with the preceding 13-year period, deficiencies remain. Urologists can play an important role in trial design, recruitment, and execution, and ensuring trial methodology and reporting quality is prioritized.

INTRODUCTION/BACKGROUND:While level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) for patients with muscle-invasive bladder cancer (MIBC), its uptake has been underwhelming, even in academic centres. Our aim was to determine if the initiation of a multidisciplinary bladder cancer clinic (MDBCC) in 2008 at our institution, where patients are assessed simultaneously by bladder cancer-focused urologists and radiation oncologists with easy access to a medical oncologist, was associated with an increased use of NAC. METHODS:Patients with MIBC initiating treatment between July 2000 and June 2013 were identified and classified by academic year (July 1 to June 30). Time-series analyses using interventional autoregressive integrated moving average (ARIMA) models with ramp intervention functions were then conducted. A sensitivity analysis was performed on clinical N0 patients. RESULTS:The cohort included 278 patients: 168 from 2000-2007 and 110 from 2008-2012 (academic years). Forty-two (15.1%) patients received NAC and 74 (26.6%) received adjuvant chemotherapy (AC). Overall the proportion of patients receiving NAC increased from 7.7% before the MDBCC to 47.6% in 2012 (Interventional ARIMA p=0.036). The results were similar when restricting to cN0 patients (p<0.001). NAC use gradually increased over time regardless of MDBCC attendance, although the proportion of patients receiving NAC appears to have risen more sharply among MDBCC attendees. CONCLUSIONS:At our institution, the initiation of the MDBCC was temporally associated with increased use of NAC. In addition to multidisciplinary collaboration, having a critical mass of NAC physician advocates and support from institutional leaders are essential to the uptake of NAC.

PURPOSE/OBJECTIVE:Metformin, a first-line oral therapy for diabetes, has anticancer properties. Our objective was to evaluate the association between metformin use and oncologic outcomes in diabetic patients undergoing radical cystectomy (RC) for bladder cancer (BC). METHODS:A single-institution retrospective cohort (January 1997-June 2013) of diabetic patients undergoing RC was assembled. Medication use was assessed at time of surgery. Outcome measures were recurrence-free survival (RFS), BC-specific survival (BCSS), and overall survival (OS). Multivariable Cox proportional hazards models were used. To create parsimonious models, the change of estimate approach (10% threshold) was used as a variable selection strategy for final model inclusion separately for each outcome measure. RESULTS:Of 421 patients, 85 (20%) had diabetes. There were 39 (46%) patients on metformin therapy. Among diabetic patients, there were 21 patients with BC recurrence, 16 who died of BC, and 30 who died overall. In univariate analyses, metformin use among diabetic patients was associated with improved RFS (hazard ratio = 0.54, 95% CI: 0.33-0.88, P = 0.013) and trended toward improved BCSS (hazard ratio = 0.65, 95% CI: 0.40-1.07, P = 0.087), but not with OS (P = 0.87). In multivariable models, metformin use among diabetic patients was associated with significantly improved RFS (adjusted hazard ratio = 0.38, 95% CI: 0.20-0.72, P = 0.003) and BCSS (adjusted hazard ratio = 0.57, 95% CI: 0.35-0.91, P = 0.019), but not with OS (P = 0.89). Use of other oral hypoglycemic agents or insulin was not associated with oncologic outcomes. CONCLUSIONS:Our study is among the first to report an association between metformin use and improved RFS and BCSS in diabetic patients undergoing RC. Given its low cost and demonstrated safety among nondiabetic patients, further studies are warranted to evaluate potential therapeutic and preventive roles of metformin in BC.

PURPOSE/OBJECTIVE:The number of lymph nodes removed at surgery for various malignancies has diagnostic and prognostic value. However, there are limited data on the significance of the number of nodes removed at retroperitoneal lymph node dissection performed for testicular nonseminoma germ cell tumors. MATERIALS AND METHODS/METHODS:From 1979 to 2012 primary open retroperitoneal lymph node dissection was performed by a single experienced surgeon for clinical stage I/II testicular nonseminoma germ cell tumor in 157 patients. Node count was available in 111 cases (71%). Factors associated with total node count and nodes with viable cancer were assessed by linear regression. The association between node count and time to relapse was assessed by multivariate Cox proportional hazards models controlled for adjuvant chemotherapy. RESULTS:The median total lymph node count was 28 (IQR 19-38). Patient age, cancer laterality, body mass index, clinical stage, time from orchiectomy to retroperitoneal lymph node dissection, pathologist and lymph node dissection year were not associated with total lymph node count. A viable germ cell tumor was found in 70 patients (63%). Total node yield was not associated with nodal cancer metastasis. After lymph node dissection 17 patients (16%) received adjuvant chemotherapy. At a median 57-month followup 18 cases (17%) relapsed after primary retroperitoneal lymph node dissection. Increasing total node count was associated with a decreased risk of relapse on univariate and multivariate analysis (HR 0.96, 95% CI 0.92-0.99, p = 0.03 and HR 0.94, 95% CI 0.89-0.99, p = 0.017, respectively). CONCLUSIONS:No analyzed clinical or pathological variable was associated with the node yield of primary retroperitoneal lymph node dissection. However, there may be a relationship between the total node yield at retroperitoneal lymph node dissection and the risk of relapse.