Fixed-effect Versus Random-effects Models for Meta-analyses: Random-effects Models.

Random-effects models can account for variability both within and between studies. This makes them suitable for meta-analyses in surgery, where there is often significant heterogeneity between studies or heterogeneity owing to intrinsic differences attributable to patient or population factors.

Diagnosis, Management, and Follow-Up of the Incidentally Discovered Adrenal Mass: CUA Guideline Endorsed by the AUA.

PURPOSE: Incidental adrenal masses are common and require a multidisciplinary approach to evaluation and management that includes family physicians, urologists, endocrinologists, and radiologists. The purpose of this guideline is to provide an updated approach to the diagnosis, management, and follow-up of adrenal incidentalomas, with a special focus on the areas of discrepancy/controversy existing among the published guidelines from other associations. MATERIALS AND METHODS: This guideline was developed by the Canadian Urological Association (CUA) through a working group comprised of urologists, endocrinologists, and radiologists and subsequently endorsed by the American Urological Association (AUA). A systematic review utilizing the GRADE approach served as the basis for evidence-based recommendations with consensus statements provided in the absence of evidence. For each guideline statement, the strength of recommendation was reported as weak or strong, and the quality of evidence was evaluated as low, medium, or high. RESULTS: The CUA working group provided evidence- and consensus-based recommendations based on an updated systematic review and subject matter expertise. Important updates on evidence-based radiological evaluation and hormonal testing are included in the recommendations. This guideline clarifies which patients may benefit from surgery and highlights where short term surveillance is appropriate. CONCLUSION: Incidentally detected adrenal masses require a comprehensive assessment of hormonal function and oncologic risk. This guideline provides a contemporary approach to the appropriate clinical, radiographic, and endocrine assessments required for the evaluation, management, and follow-up of patients with such lesions.

Predicting the recurrence risk of renal cell carcinoma after nephrectomy: potential role of CT-radiomics for adjuvant treatment decisions.

OBJECTIVES: Previous trial results suggest that only a small number of patients with non-metastatic renal cell carcinoma (RCC) benefit from adjuvant therapy. We assessed whether the addition of CT-based radiomics to established clinico-pathological biomarkers improves recurrence risk prediction for adjuvant treatment decisions. METHODS: This retrospective study included 453 patients with non-metastatic RCC undergoing nephrectomy. Cox models were trained to predict disease-free survival (DFS) using post-operative biomarkers (age, stage, tumor size and grade) with and without radiomics selected on pre-operative CT. Models were assessed using C-statistic, calibration, and decision curve analyses (repeated tenfold cross-validation). RESULTS: At multivariable analysis, one of four selected radiomic features (wavelet-HHL_glcm_ClusterShade) was prognostic for DFS with an adjusted hazard ratio (HR) of 0.44 (p = 0.02), along with American Joint Committee on Cancer (AJCC) stage group (III versus I, HR 2.90; p = 0.002), grade 4 (versus grade 1, HR 8.90; p = 0.001), age (per 10 years HR 1.29; p = 0.03), and tumor size (per cm HR 1.13; p = 0.003). The discriminatory ability of the combined clinical-radiomic model (C = 0.80) was superior to that of the clinical model (C = 0.78; p < 0.001). Decision curve analysis revealed a net benefit of the combined model when used for adjuvant treatment decisions. At an exemplary threshold probability of ≥ 25% for disease recurrence within 5 years, using the combined versus the clinical model was equivalent to treating 9 additional patients (per 1000 assessed) who would recur without treatment (i.e., true-positive predictions) with no increase in false-positive predictions. CONCLUSION: Adding CT-based radiomic features to established prognostic biomarkers improved post-operative recurrence risk assessment in our internal validation study and may help guide decisions regarding adjuvant therapy. KEY POINTS: In patients with non-metastatic renal cell carcinoma undergoing nephrectomy, CT-based radiomics combined with established clinical and pathological biomarkers improved recurrence risk assessment. Compared to a clinical base model, the combined risk model enabled superior clinical utility if used to guide decisions on adjuvant treatment.

Surgeon-level versus hospital-level quality variance in kidney cancer surgery.

PURPOSE: 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: 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.

A Matched Analysis of Active Surveillance Versus Nephrectomy for T1a Small Renal Masses.

While patients with a small renal mass (SRM) on active surveillance (AS) experience excellent metastasis-free survival (MFS) and cancer-specific survival (CSS), differences in overall survival (OS) observed may be explained by selection of older/comorbid patients for AS. Few studies have evaluated AS versus primary intervention in clinically balanced groups. We identified patients aged 55-75 yr with an SRM (≤4 cm, T1a) in our institutional database (2000-2020). Patients from AS and nephrectomy subgroups were matched exactly for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, biopsy status, and histology. The primary outcomes were OS and an event-free survival (EFS) composite that included OS, CSS, MFS, progression, or systemic therapy, which we tested in Cox proportional-hazards models. We identified 377 patients (205 AS, 172 nephrectomy). The cohort was balanced after matching (n = 110; mean age 64 yr, 77% male, and 75% ECOG score 0). In each arm, 47% were biopsied (predominantly clear-cell histology). The predicted 5-yr OS was 96% for the nephrectomy group and 95% for the AS group (hazard ratio for nephrectomy vs AS [HR] 0.83, 95% confidence interval [CI] 0.13-5.32; p = 0.8), with corresponding 5-yr EFS rates of 93% and 96% (HR 1.88, 95% CI 0.35-10.15; p = 0.5). Among SRM cases well matched for age and overall health status, we observed higher 5-yr OS and EFS rates for AS than previously reported; the rates were not significantly different from those after nephrectomy. The matched characteristics of our population are similar to those for treatment arms in contemporary cohorts and the results support the safety of AS in younger, healthier patients. PATIENT SUMMARY: While it has been shown that active surveillance for small kidney tumors is safe in older and more frail patients, its safety in younger, healthier patients has not been confirmed. We compared outcomes for patients aged 55-75 yr who were managed with surgery or active surveillance, and were similar in age and overall health. The probability of death after 5 years was low overall and not significantly different between the groups, suggesting that active surveillance is safe in routine clinical practice.

The Importance of Repeat Imaging Prior to Treatment Decision-making in Testicular Cancer: Commentary From the Inaugural Global Society of Rare Genitourinary Tumors Summit.

Testicular cancer is a rare cancer that often affects young and otherwise healthy patients. Imaging plays a critical role in the staging and surveillance of patients with testicular cancer. Indeterminate findings on staging or surveillance imaging, can lead to challenging management decisions for clinicians and patients. In this article, we review the importance of short-interval, repeat imaging for several scenarios faced by patients with testicular cancer and their clinicians. The challenging scenarios and recommendations provided in this article summarize the discussion from the inaugural Global Society of Rare Genitourinary Tumors (GSRGT) Summit held on December 11-12, 2020.

Extended-duration thromboprophylaxis for abdominopelvic surgery: Development and evaluation of a risk-stratified patient decision aid to facilitate shared decision making.

Background: Extended-duration thromboprophylaxis is used to decrease risk of venous thromboembolism (VTE) after surgery but may increase the risk of bleeding. The decision to complete a course of extended-duration thromboprophylaxis can be challenging. Objective: The objective of this study was to develop an acceptable patient decision aid (PtDA) to facilitate shared decision making for the use of extended-duration thromboprophylaxis following major abdominal surgery. Methods: An evidence-based, risk-stratified PtDA was created. The evidence on benefits and harms of a 28-day postoperative course of low-molecular-weight heparin (LMWH) versus in-hospital prophylaxis only were synthesized. Outcomes included minor bleeding, major bleeding, clinically significant VTE, and fatal VTE. Risks were calculated and reported by Caprini score. Alpha testing of the PtDA draft with various stakeholders was performed using a 10-question survey to assess acceptability of the PtDA with patients, thrombosis experts, and surgeons. The primary outcome was the acceptability of the PtDA. Results: Acceptability testing was performed with 11 patients, 11 thrombosis experts, and 11 surgeons. Most responders felt the language on the PtDA was easy to follow (28/33, 85%), and that the information was well balanced between management options (9/11 [82%] patients; 17/21 [80%] clinicians). Most patients (9/11, 82%) and clinicians (18/22, 82%) believed it would be a useful clinical tool, and were satisfied with the overall quality of the PtDA (27/33, 82%). Conclusions: A risk-stratified, evidence-based PtDA was created to facilitate shared decision making for the use of extended-duration LMWH following major abdominal surgery. This clinical tool was acceptable with patients and physicians and is available at https://decisionaid.ohri.ca/decaids.html.

A survey of physician perception and practices regarding pharmacological thromboprophylaxis during chemotherapy for bladder cancer.

INTRODUCTION: Patients with advanced bladder cancer receiving chemotherapy have a high risk of venous thromboembolism (VTE); however, we hypothesized these patients were not routinely offered thromboprophylaxis. The objective of this study was to characterize practice patterns and perceptions of Canadian urologic and medical oncologists, and to identify research needs regarding thromboprophylaxis for patients with bladder cancer. METHODS: An online survey was distributed to Canadian urologic and medical oncologists who manage advanced bladder cancer. The survey explored physician opinions regarding VTE rates, risk stratification scores, thromboprophylaxis use in different treatment settings, and interest in clinical trials. RESULTS: Seventy physicians were invited and 36 (51%) completed the survey, including 20 (56%) urologic oncologists and 16 (44%) medical oncologists. Most respondents (35; 97%) believed that exposure to platinum chemotherapy increases VTE risk. For patients receiving neoadjuvant chemotherapy, 34 (94%) respondents estimated the risk of VTE to be 10% or higher, yet 25 (69%) indicated they do not routinely recommend thromboprophylaxis. Physicians frequently (10; 40%) defer the decision to another physician, while eight (32%) believe there is not enough evidence to guide best management. Similar responses were obtained for metastatic patients. Almost all (94%) respondents were interested in participating in a thromboprophylaxis trial for patients with bladder cancer. CONCLUSIONS: Patients with bladder cancer receiving chemotherapy in Canada are not routinely offered thromboprophylaxis. We found strong interest among Canadian oncologists to participate in clinical trials examining this topic.

Venous thromboembolism risk in patients receiving neoadjuvant chemotherapy for bladder cancer.

INTRODUCTION: There is limited evidence to inform thromboprophylaxis use for patients receiving neoadjuvant chemotherapy prior to surgery in bladder cancer. We sought to determine the incidence of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy and cystectomy. We also assessed if the Khorana score was associated with VTE risk. METHODS: A retrospective cohort study was performed on consecutive patients who received a radical cystectomy for bladder cancer at The Ottawa Hospital between January 2016 and August 2020. Demographic information, chemotherapy data, operative characteristics, VTE and bleeding outcomes were collected from the start of treatment to 90 days postoperative. A Khorana score was calculated for each patient who received neoadjuvant chemotherapy. The primary outcome for this study was the incidence of VTE from the time the patient started treatment with neoadjuvant chemotherapy until 90 days post-cystectomy. Secondary outcomes included risk factors for VTE during neoadjuvant chemotherapy. RESULTS: Among 181 radical cystectomy cases during the study period, 123 had muscle-invasive disease and 72 (39.8%) received neoadjuvant chemotherapy. Eighteen (25.0%) patients who received neoadjuvant chemotherapy and radical cystectomy developed a VTE from the start of chemotherapy to 90 days postoperative. Thirteen of the 18 VTEs (72%) occurred while the patient was receiving chemotherapy. In multivariable analysis, the only factor associated with a significantly increased risk of VTE was treatment with neoadjuvant chemotherapy (Relative risk (RR) 3.05, 95% confidence interval [CI] 1.16-8.02; P = 0.02). A higher Khorana score was not associated with an increased risk of VTE in patients who received neoadjuvant chemotherapy (RR = 0.33, 95% CI 0.08-1.28, P = 0.11). One (1.4%) patient had a major bleeding event during neoadjuvant chemotherapy. CONCLUSIONS: Patients receiving neoadjuvant chemotherapy and radical cystectomy are at very high-risk of VTE. Prospective studies that assess the benefits and harms of pharmacologic thromboprophylaxis in this population are needed.

Development, implementation, and uptake of a novel Canadian Resident Matching Service (CaRMS) residency recruitment committee strategy in the era of COVID-19.

INTRODUCTION: Given restrictions on electives outside of medical students' home institutions during the COVID-19 pandemic, the objective of this study was to create a novel recruitment strategy for the University of Ottawa's (uOttawa) urology residency program. METHODS: A steering committee was formed and created a three-part recruitment strategy that included a new uOttawa urology website, a residency program social media campaign (Twitter and Instagram), and a virtual open house (VOH). Descriptive data from the website and Instagram and Twitter accounts were collected. Attendees of the VOH completed a mixed-methods survey, which collected quantitative and qualitive responses assessing aspects of the VOH and virtual resource use. RESULTS: From August 1 to December 31, 2020, the uOttawa urology website had 1707 visits. The Twitter account had a total of 29 000 views with 1000-5000 views per tweet. Thirty-one candidates attended the VOH. Survey responders reported that the most frequently used resources to gain knowledge of the program were the website (81%) and Twitter account (71%). The most helpful and informative resources were the uOttawa urology website, the VOH, and direct conversations with residents arranged through the website. Despite not having completed an elective, 26 students (84%) felt they had an understanding of what it might feel like to train in the program. Suggestions by students for future initiatives included one-on-one virtual meetings, another VOH, and more information on selection processes. CONCLUSIONS: A multifaceted, virtual recruitment strategy can be implemented to improve candidate understanding and engagement with residency programs while visiting elective opportunities remain limited.

Optimizing the management of patients with small renal masses in a Canadian context: A Markov decision-analysis model.

INTRODUCTION: The management of patients with a small renal mass (SRM) varies significantly. The objective of this study was to determine which initial management strategy resulted in the greatest quality-adjusted life months (QALM) for an index patient with a SRM. METHODS: A Markov decision analysis was used to determine the effect of 1) treating patients with a partial nephrectomy (PN); 2) active surveillance (AS); and 3) renal mass biopsy on QALM over a 10-year horizon. All relevant health states were modelled. Biopsy sensitivity and specificity were modelled assuming an 80% prevalence of cancer using procedural pathology as the gold standard. Health state utilities were obtained from the Tufts Medical Centre Cost-Effective Analysis Registry. Deterministic sensitivity analyses were used to test key assumptions. RESULTS: Over a 10-year time horizon for a 70-year-old male with a 2 cm SRM, the biopsy strategy resulted in 38.07 QALM, whereas treating all patients with PN resulted in 37.69 QALM and AS in 36.25 QALM. The model was most sensitive to the probability that a patient would remain alive at baseline. Biopsy was the preferred strategy when sensitivity was greater than 77%. As the underlying probability of cancer increased, the threshold of renal mass biopsy sensitivity to still favor biopsy increased. CONCLUSIONS: Renal mass biopsy is the preferred initial management strategy for an index patient with a SRM to optimize QALM. When the probability of cancer is high, centers should aim for a sensitivity of at least 77% in order to consider a biopsy as the first strategy.

Evaluating the acceptability of an online patient decision aid for the surgical management of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

INTRODUCTION: The growing number of surgical options available to treat benign prostatic hyperplasia (BPH), may overwhelm patients and urologists when deciding on an optimal treatment. Therefore, we developed an online patient decision aid (PtDA) that includes all guideline-approved surgical modalities. The objective of this study was to assess the acceptability of the PtDA among former BPH surgery patients and urologists that treat BPH surgically. METHODS: The International Patient Decision Aids Standards were used to develop a PtDA that includes monopolar transurethral resection of the prostate (TURP), bipolar TURP, GreenLight photovaporization, endoscopic enucleation of the prostate, Rezum, Urolift, Aquablation, open retropubic prostatectomy, and robotic simple prostatectomy as management options. Eleven urologists that regularly treat BPH and 19 patients who received BPH surgery were recruited. Alpha-testing was performed using a validated acceptability scoring system. RESULTS: For all sections of the PtDA, most urologists agreed that the language used was easy to follow (91.9%), that the amount of information provided was adequate (63.6%), that the length of the PtDA was appropriate (63.6%), and that the outcomes reported were correct (81.8%). All 19 patient participants agreed that the language used was easy to follow, and most found that the amount of information provided was adequate (84.2%), that the length of the PtDA was appropriate (84.2%), and that the outcomes reported were well-explained (89.5%). CONCLUSIONS: Our PtDA was found to be acceptable among urologists and patients. These results demonstrate that most of the participants either recommend the use of this tool or plan to incorporate it in their clinical practice.

Evidence-based Urology: Surrogate Endpoints - Con.

Surrogate endpoints have the potential to expedite results from clinical trials. However, a surrogate endpoint may not always be a patient-important outcome. Surrogate endpoints must be validated to ensure that they do not expose patients to unnecessary treatment-related toxicity.

Timing of Perioperative Pharmacologic Thromboprophylaxis Initiation and its Effect on Venous Thromboembolism and Bleeding Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Perioperative thromboprophylaxis guidelines offer conflicting recommendations on when to start thromboprophylaxis. As a result, there is considerable variation in clinical practice, which can lead to worse patient outcomes. The objective of this study was to evaluate the association between the start time of perioperative thromboprophylaxis with venous thromboembolism (VTE) and bleeding outcomes. STUDY DESIGN: Embase, Medline, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were searched on October 23, 2020. Randomized controlled trials that evaluated VTE and/or bleeding among groups receiving the initial dose of pharmacologic thromboprophylaxis at different times preoperatively, intraoperatively, or postoperatively were included. Only trials that randomized patients to the same medication among groups were eligible. Studies on any type of operation were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The Cochrane Collaboration risk of bias tool was used. The review was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42019142079). The outcomes of interest were VTE and bleeding. Prespecified subgroup analyses of studies including orthopaedic and nonorthopaedic operations were performed. RESULTS: A total of 22 trials (n = 17,124 patients) met eligibility criteria. Pooled results showed a nonstatistically significant decrease in the rate of VTE with preoperative initiation of thromboprophylaxis compared with postoperative initiation (risk ratio 0.77; 95% CI, 0.55 to 1.08; I2 = 0%, n = 1,933). There was also a nonstatistically significant increase in the rate of bleeding with preoperative compared with postoperative initiation (risk ratio 1.17; 95% CI, 0.94 to 1.46; I2 = 35%, n = 2,752). Risk of bias was moderate. Heterogeneity between studies was low (I2 = 0% to 35%). CONCLUSIONS: This meta-analysis found a nonstatistically significant decrease in the rate of VTE and an increase in the rate of bleeding when thromboprophylaxis was initiated preoperatively compared with postoperatively.

The evolving role of germline genetic testing and management in prostate cancer: Report from the Princess Margaret Cancer Centre international retreat.

Prostate cancer is a significant cause of cancer mortality. It has been well-established that certain germline pathogenic variants confer both an increased risk of being diagnosed with prostate cancer and dying of prostate cancer.1 There are exciting developments in both the availability of genetic testing and opportunities for improved treatment of patients.On August 19, 2020, the Princess Margaret Cancer Centre in Toronto, Ontario, hosted a virtual retreat, bringing together international experts in urology, medical oncology, radiation oncology, medical genetics, and translational research, as well as a patient representative. We are pleased to provide this manuscript as a review of those proceedings for Canadian clinicians.We highlighted several needs for future research and policy action based on this meeting:Increased access to funding for germline testing for the common genetic disorders associated with increased risk of prostate cancer.More research into identifying genetic factors influencing risk stratification, treatment response, and outcomes of prostate cancer within Canadian populations at higher genetic risk for prostate cancer.Added awareness about genetic risk factors among the Canadian public.Development of patient-specific and reported outcomes research in tailored care for patients at increased genetic risk of prostate cancer.Creation of multidisciplinary clinics that specialize in tailored care for patients at increased genetic risk of prostate cancer.

A Clinical Trial of Prophylactic Prostatectomy for BRCA2 Mutation Carriers: Is Now the Time?

The greater availability and use of genetic testing have improved our ability to determine that men with BRCA2 mutations are at significantly higher risk of developing and dying of prostate cancer. We should continue research efforts in secondary prevention for this population, but must also explore primary preventative strategies such as prophylactic prostatectomy. Efforts are under way at our institution for a clinical trial in this area.