Faculty Bibliography

PURPOSE:Robust prediction of progression on active surveillance (AS) for prostate cancer can allow for risk-adapted protocols. To date, models predicting progression on AS have invariably used traditional statistical approaches. We sought to evaluate whether a machine learning (ML) approach could improve prediction of progression on AS. PATIENTS AND METHODS:We performed a retrospective cohort study of patients diagnosed with very-low or low-risk prostate cancer between 1997 and 2016 and managed with AS at our institution. In the training set, we trained a traditional logistic regression (T-LR) classifier, and alternate ML classifiers (support vector machine, random forest, a fully connected artificial neural network, and ML-LR) to predict grade-progression. We evaluated model performance in the test set. The primary performance metric was the F1 score. RESULTS:Our cohort included 790 patients. With a median follow-up of 6.29 years, 234 developed grade-progression. In descending order, the F1 scores were: support vector machine 0.586 (95% CI 0.579 - 0.591), ML-LR 0.522 (95% CI 0.513 - 0.526), artificial neural network 0.392 (95% CI 0.379 - 0.396), random forest 0.376 (95% CI 0.364 - 0.380), and T-LR 0.182 (95% CI 0.151 - 0.185). All alternate ML models had a significantly higher F1 score than the T-LR model (all p <0.001). CONCLUSION:In our study, ML methods significantly outperformed T-LR in predicting progression on AS for prostate cancer. While our specific models require further validation, we anticipate that a ML approach will help produce robust prediction models that will facilitate individualized risk-stratification in prostate cancer AS.

PURPOSE/OBJECTIVE:Randomized trials from Africa demonstrate that circumcision reduces the risk of acquiring human immunodeficiency virus (HIV) among males. However, few studies have examined this association in Western populations. We sought to evaluate the association between circumcision and the risk of acquiring HIV among males from Ontario, Canada. MATERIALS AND METHODS/METHODS:We conducted a population-based matched cohort study of residents in Ontario, Canada. We identified males born in Ontario who underwent circumcision at any age between 1991 and 2017. The comparison group consisted of age-matched males who did not undergo circumcision. The primary outcome was incident HIV. We used cause-specific hazard models to evaluate the hazard of incident HIV. We performed several sensitivity analyses to evaluate the robustness of our results: matching on institution of birth, varying the minimum followup period, and simulating various false-negative and false-positive thresholds. RESULTS:We studied 569,950 males, including 203,588 who underwent circumcision and 366,362 who did not. The vast majority of circumcisions (83%) were performed prior to age 1 year. In the primary analysis, we found no significant difference in the risk of HIV between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.72 to 1.35). In none of the sensitivity analyses did we find an association between circumcision and risk of HIV. CONCLUSIONS:We found that circumcision was not independently associated with the risk of acquiring HIV among males from Ontario, Canada. Our results are consistent with clinical guidelines that emphasize safe-sex practices and counseling over circumcision as an intervention to reduce the risk of HIV.

INTRODUCTION/BACKGROUND:Active surveillance (AS) is an established approach in the management of low-risk, localized prostate cancer. While the use of AS to manage intermediate-risk (IR) disease has gradually increased over time, there remains uncertainty with regards to its safety, with only a minority of IR patients currently being managed with this approach. MATERIALS AND METHODS/METHODS:We conducted a narrative review based on an analysis of the literature focusing on articles describing AS for IR prostate cancer. We focus on the uncertainty surrounding AS in IR disease by discussing variations in the definitions and guideline recommendations associated with IR disease, and describing the limitations of the evidence from observational studies and randomized trials. CONCLUSION/CONCLUSIONS:The safety of AS for IR disease remains unknown, given the lack of randomized trials and the limitations of the current observational studies. Further research is needed to identify select patients with IR prostate cancer that can be managed safely with AS.

BACKGROUND:Robust prediction of survival can facilitate clinical decision-making and patient counselling. Non-Caucasian males are underrepresented in most prostate cancer databases. We evaluated the variation in performance of a machine learning (ML) algorithm trained to predict survival after radical prostatectomy in race subgroups. METHODS:We used the National Cancer Database (NCDB) to identify patients undergoing radical prostatectomy between 2004 and 2016. We grouped patients by race into Caucasian, African-American, or non-Caucasian, non-African-American (NCNAA) subgroups. We trained an Extreme Gradient Boosting (XGBoost) classifier to predict 5-year survival in different training samples: naturally race-imbalanced, race-specific, and synthetically race-balanced. We evaluated performance in the test sets. RESULTS:A total of 68,630 patients met inclusion criteria. Of these, 57,635 (84%) were Caucasian, 8173 (12%) were African-American, and 2822 (4%) were NCNAA. For the classifier trained in the naturally race-imbalanced sample, the F1 scores were 0.514 (95% confidence interval: 0.513-0.511), 0.511 (0.511-0.512), 0.545 (0.541-0.548), and 0.378 (0.378-0.389) in the race-imbalanced, Caucasian, African-American, and NCNAA test samples, respectively. For all race subgroups, the F1 scores of classifiers trained in the race-specific or synthetically race-balanced samples demonstrated similar performance compared to training in the naturally race-imbalanced sample. CONCLUSIONS:A ML algorithm trained using NCDB data to predict survival after radical prostatectomy demonstrates variation in performance by race, regardless of whether the algorithm is trained in a naturally race-imbalanced, race-specific, or synthetically race-balanced sample. These results emphasize the importance of thoroughly evaluating ML algorithms in race subgroups before clinical deployment to avoid potential disparities in care.

INTRODUCTION/BACKGROUND:Squamous cell carcinoma (SCC) of the penis is a rare disease comprising 1% of all male cancer. Options for the management of cT1-T2 cN0 penile SCC include partial penectomy (PP), considered the standard, and brachytherapy (BT), which offers acceptable local disease control and organ preservation. The purpose of our study was to assess and describe the oncological outcome for both treatments in a tertiary care center. METHODS:We performed a contemporary retrospective study of patients with early-stage penile cancer treated surgically or by BT at a tertiary center between 2000 and 2016. Demographic, management, and followup data were obtained from an institutional database. Descriptive statistics and survival analysis using Kaplan-Meier plots were calculated. Local and regional recurrences were compared in both groups (BT vs. PP). RESULTS:A total of 51 patients with cT1-T2N0 penile SCC treated with BT (35) and PP (16) were analyzed. Median followup was 37.1 (13.9-68) and 25.4 months (18-52.3) for the BT and PP groups, respectively. Recurrence developed in seven (20%) patients treated with BT. Median time to recurrence was 35.2 months (range 2.9-95.8). No recurrences were reported in patients treated with PP. Forty-four (86.2%) patients were alive with no evidence of disease at the last followup. Overall survival was 62.7%. Complications after primary tumor treatment were urethral stenosis (15.7%), penile necrosis (7.8%), and local infection (2%). CONCLUSIONS:PP provides acceptable local control with organ preservation in early-stage penile SCC. BT was able to offer organ preservation in 69% of men. Future prospective studies are needed to compare other organ-conserving treatment modalities with PP.

INTRODUCTION/BACKGROUND:Despite the high prevalence rates of urinary retention in sub-Saharan Africa, regional deficiencies in urological care have culminated in inadequate medical management and a backlog of urology cases. Our study examined the efficacy and safety of a surgical camp enlisting local non-urologists performing simple open prostatectomy on the rate of chronic catheter usage secondary to urinary retention. METHODS:We reported on a prospective case series of patients with chronic indwelling catheters who underwent open simple prostatectomy during a one-week urology camp in the Machinga District of Malawi. All operations were performed by a locally trained general surgeon and a clinical officer. RESULTS:Twenty-three (47.9%) of 48 male patients with urinary retention assessed for eligibility for open simple prostatectomy were deemed eligible and underwent the procedure. Of the patients who underwent an open simple prostatectomy, histopathological findings demonstrated benign prostatic hyperplasia in 19 patients (82.6%), while six patients (26.1%) had coincidental malignancy. At postoperative followup, the entire cohort was catheter-free and reported regular sexual activity and the ability to return to work, while 87.0% noted improvements in social integration and 34.8% cited higher self-esteem. Two patients required treatment for infection and one patient experienced fascial dehiscence. Two months following prostatectomy, all patients were catheter-free and able to void independently. CONCLUSIONS:Local surgical practitioners without formal urology training can successfully perform open simple prostatectomy to relieve patients of chronic indwelling catheters and assist in addressing the disease burden in a low-resource setting.

INTRODUCTION/BACKGROUND:The benefit of partial nephrectomy (PN) compared to radical nephrectomy (RN) for T1a renal cell carcinoma (RCC) remains uncertain, with observational studies conflicting with level 1 evidence. Therefore, the purpose of this population-based study was to compare long-term outcomes in patients undergoing PN or RN for T1a RCC. METHODS:We studied 5670 patients in Ontario, Canada undergoing PN or RN for T1a RCC. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), chronic kidney disease (CKD), renal replacement therapy, and myocardial infarction (MI). We used multivariable Cox proportional hazard models to evaluate the association between PN or RN and these outcomes. A sensitivity analysis was performed in patients with a preoperative serum creatinine available. RESULTS:Median followup was 77 months. Compared to RN, PN was associated with significantly improved OS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.84), reduced risk of CKD (HR 0.18, 95% CI 0.12-0.27), and improved CSS (HR 0.45, 95% CI 0.30-0.65). The risk of MI was not significantly different between groups (HR 0.91, 95% CI 0.62-1.34). Few patients (n=15) required renal replacement therapy. In the sensitivity analysis, the association between type of surgery and OS and CKD persisted, while the association with CSS did not. CONCLUSIONS:Our study found that in patients undergoing surgery for T1a RCC, PN was associated with improved OS and reduced risk of CKD compared to RN. However, few patients in either group required renal replacement therapy.

INTRODUCTION/BACKGROUND:We aimed to study the association of ethnicity on semen parameters and hormones in patients presenting with infertility. METHODS:Data from men presenting for infertility assessment were prospectively collected and retrospectively reviewed. Demographic and clinical history was self-reported. Semen analysis included volume, count, motility, morphology, and vitality. The 2010 World Health Organization cutoffs were used. Baseline total testosterone and follicle-stimulating hormone (FSH) levels were recorded. Ethnicity data was classified as Caucasian, African Canadian, Asian, Indo-Canadian, Native Canadian, Hispanic, and Middle Eastern. All patients with complete data were included and statistical analysis was performed. RESULTS:A total of 9079 patients were reviewed, of which 3956 patients had complete data. Of these, 839 (21.2%) were azoospermic. After adjusting for age, African Canadians (odds ratio [OR] 1.70; 95% confidence interval [CI] 1.28-2.25) and Asians (1.34; 95% CI 1.11-1.62) were more likely to be azoospermic compared to Caucasians. Similarly, African Canadians (OR 1.75; 95% CI 1.33-2.29) were more likely to be oligospermic and Asians (OR 0.82; 95% CI 0.70-0.97) less likely to be oligospermic. Low volume was found in African Canadian (OR 1.42; 95% CI 1.05-1.91), Asians (OR 1.23; 95% CI 1.01-1.51), and Indo-Canadians (OR 1.47; 95% CI 1.01-2.13). Furthermore, Asians (OR 0.73; 95% CI 0.57-0.93) and Hispanics (OR 0.58; 95% CI 034-0.99) were less likely to have asthenospermia. Asians (OR 0.73; 95% CI 0.57-0.94) and Indo-Canadians (OR 0.58; 95% CI 0.35-0.99) were less likely to have teratozospermia. No differences were seen for vitality. No differences were seen for FSH levels, however, Asians (p<0.01) and Indo-Canadians (p<0.01) were more likely to have lower testosterone. CONCLUSIONS:Our study illustrates that variations in semen analyses and hormones exist in men with infertility. This may provide insight into the workup and management for infertile men from different ethnicities.