Faculty Bibliography

BACKGROUND:Prediction models based on machine learning (ML) methods are being increasingly developed and adopted in health care. However, these models may be prone to bias and considered unfair if they demonstrate variable performance in population subgroups. An unfair model is of particular concern in bladder cancer, where disparities have been identified in sex and racial subgroups. OBJECTIVE:This study aims (1) to develop a ML model to predict survival after radical cystectomy for bladder cancer and evaluate for potential model bias in sex and racial subgroups; and (2) to compare algorithm unfairness mitigation techniques to improve model fairness. METHODS:-score. The primary metric for model fairness was the equalized odds ratio (eOR). We compared 3 algorithm unfairness mitigation techniques to improve eOR. RESULTS:-scores of 0.86, 0.904, and 0.824 in the full, Black male, and Asian female test sets, respectively. CONCLUSIONS:The ML model predicting survival after radical cystectomy exhibited bias across sex and racial subgroups. By using algorithm unfairness mitigation techniques, we improved algorithmic fairness as measured by the eOR. Our study highlights the role of not only evaluating for model bias but also actively mitigating such disparities to ensure equitable health care delivery. We also deployed the first web-based fair ML model for predicting survival after radical cystectomy.

OBJECTIVE:To characterize differences in the management of small renal masses among disaggregated race/ethnic subgroups. MATERIAL AND METHODS/METHODS:We used the National Cancer Database to identify patients diagnosed with clinically localized kidney cancer and tumor size ≤4cm. We studied 16 predefined racial/ethnic subgroups and compared 1) the use of surveillance for tumors <2cm and 2) the use of radical nephrectomy for tumors ≤4cm. We used multivariable logistic regression to evaluate the independent association of race/ethnicity with management, adjusting for baseline characteristics. We also compared our disaggregated analyses to the 6 National Institute of Health aggregate race categories. RESULTS:We identified 286,063 patients that met inclusion criteria. For tumors <2cm, Black Non-Hispanic (aOR 1.43) and Mexican patients (aOR 1.29) were significantly more likely to undergo surveillance compared to White patients. For tumors ≤4cm, Black Non-Hispanic (aOR 1.43), Filipino (aOR 1.28), Japanese (aOR 1.28), Mexican (aOR 1.32), and Native Indian patients (aOR 1.15) were significantly more likely to undergo radical nephrectomy compared to White patients. When comparing our disaggregated analyses to the NIH categories, we found that many disaggregated race/ethnic subgroups had associations with management strategies that were not represented by their aggregated group. CONCLUSIONS:In this study, we found that the use of surveillance for tumors <2cm and radical nephrectomy for tumors ≤4cm varied significantly among certain race/ethnic subgroups. Our disaggregated approach provides information on differences in treatment patterns in particular subgroups that warrant further study to optimize kidney cancer care for all patients.

PURPOSE/OBJECTIVE:To determine whether variance in kidney cancer surgery quality indicators (QIs) is most impacted by surgeon-level or hospital-level factors in order to inform quality improvement initiatives. MATERIALS AND METHODS/METHODS:The ICES and Veterans Affairs (VA) databases were queried for patients undergoing surgery for localized kidney cancer. Kidney cancer surgery QIs were defined within each cohort. Quality of care was benchmarked at a surgeon- vs. hospital-level to identify statistical outliers, using available clinicopathological data to adjust for differences in case-mix. Variance between surgeons and hospitals was calculated for each QI using a random-effects model. RESULTS:The QI with the greatest amount of variance explained by hospital and surgeon-level factors was proportion of cases performed with minimally invasive surgery (MIS). The majority of this variance was due to surgeon-level factors for both the VA and ICES cohorts. The proportion of cases performed using an MIS approach was also the QI with the greatest number of outlier hospitals and surgeons compared to the average performance. The proportion of partial nephrectomies performed for patients at risk of chronic kidney disease was the QI with the greatest amount of variance due to hospital-level factors for the ICES cohort. CONCLUSIONS:The proportion of localized kidney cancer cases performed using an MIS approach is the QI requiring the greatest attention. Quality improvement initiatives should focus on surgeon-level factors to increase the number of MIS cases being performed for patients with localized renal masses.

PURPOSE:The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS:We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS:The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS:Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

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.