Estimated glomerular filtration rate from the renal hypothermia trial: clinical implications.

OBJECTIVE: To assess if estimated glomerular filtration rate (eGFR) can replace measured GFR (mGFR) in partial nephrectomy (PN) trials, using data from a randomised clinical trial. PATIENTS AND METHODS: We conducted a post hoc analysis of the renal hypothermia trial. Patients underwent mGFR with diethylenetriaminepentaacetic acid (DTPA) plasma clearance preoperatively and 1 year after PN. The eGFR was calculated using the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equations incorporating age and sex, with and without race: 2009 eGFRcr(ASR) and 2009 eGFRcr(AS), and the 2021 equation that only incorporates age and sex: 2021 eGFRcr(AS). Performance was evaluated by determining the median bias, precision (interquartile range [IQR] of median bias), and accuracy (percentage of eGFR within 30% of mGFR). RESULTS: Overall, 183 patients were included. Pre- and postoperative median bias and precision were similar between the 2009 eGFRcr(ASR) (-0.2 mL/min/1.73 m2 , 95% confidence interval [CI] -2.2 to 1.7, IQR 18.8; and -2.9, 95% CI -5.1 to -1.5, IQR 15, respectively) and 2009 eGFRcr(AS) (-0.3 mL/min/1.73 m2 , 95% CI -2.4 to 1.5, IQR 18.8; and -3.0, 95% CI -5.7 to -1.7, IQR 15.0, respectively). Bias and precision were worse for the 2021 eGFRcr(AS) (-8.8 mL/min/1.73 m2 , 95% CI -10.9 to -6.3, IQR 24.7; and -12.0, 95% CI -15.8 to -8.9, IQR 23.5, respectively). Similarly, pre- and postoperative accuracy was >90% for the 2009 eGFRcr(ASR) and 2009 eGFRcr(AS) equations. Accuracy was 78.6% preoperatively and 66.5% postoperatively for 2021 eGFRcr(AS). CONCLUSION: The 2009 eGFRcr(AS) can accurately estimate GFR in PN trials and could be used instead of mGFR to reduce cost and patient burden.

Performance Feedback May Not Improve Radical Prostatectomy Outcomes: The Surgical Report Card (SuRep) Study.

PURPOSE: Oncologic, urinary, and sexual outcomes are important to patients receiving prostate cancer surgery. The objective of this study was to determine if providing surgical report cards (SuReps) to surgeons resulted in improved patient outcomes. MATERIALS AND METHODS: A prospective before-and-after study was conducted at The Ottawa Hospital. A total of 422 consecutive patients undergoing radical prostatectomy were enrolled. The intervention was provision of report cards to surgeons. The control cohort was patients treated before report card feedback (pre-SuRep), and the intervention cohort was patients treated after report card feedback (post-SuRep). The primary outcomes were postoperative erectile function, urinary continence, and positive surgical margins. RESULTS: Baseline characteristics were similar between groups. Almost all patients (99%) were continent and the majority (59%) were potent prior to surgery. Complete 1-year followup was available for 400 patients (95%). Nerve sparing surgery increased from 70% pre-SuRep to 82% post-SuRep (p=0.01). There was a nonstatistically significant increase in the proportion of patients with a positive surgical margin post-SuRep (31% pre-SuRep vs 39% post-SuRep, p=0.08). There was no difference in postoperative erectile function (17% vs 18%, p=0.7) and a decrease in continence (75% vs 65%, p=0.02) at 1 year postoperatively. CONCLUSIONS: The SuRep platform allows accurate reporting of surgical outcomes that can be used for patient counseling. However, the provision of surgical report cards did not improve functional or oncologic outcomes. Longer durations of feedback, report card modifications, or targeted interventions are likely necessary to improve outcomes.

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

PURPOSE: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. MATERIALS AND METHODS: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at 6 academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m2 at a 5% significance level. RESULTS: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/minute/1.73 m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1 year after surgery. The change in mGFR 1 year after surgery was -6.6 ml/minute/1.73 m2 in the hypothermia group and -7.8 ml/minute/1.73 m2 in the control group (mean difference 1.2 ml/minute/1.73 m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 ml/minute/1.73 m2; mean difference 0.5 ml/minute/1.73 m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. CONCLUSIONS: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

Thromboprophylaxis practice patterns and beliefs among physicians treating patients with abdominopelvic cancers at a Canadian centre.

Background: There is inadequate high-quality evidence on thromboprophylaxis for patients undergoing surgery for abdominopelvic cancer. We surveyed physicians who treat patients with abdominopelvic cancer to determine current thromboprophylaxis practice patterns and to determine where research is needed. Methods: We created an online survey with questions on thromboprophylaxis topics, including type of thromboprophylaxis used, timing of initial thromboprophylaxis dose, use of thromboprophylaxis during chemotherapy, use of extended-duration thromboprophylaxis and areas for future research. The survey questions were reviewed by external content experts to ensure they were appropriate and relevant. Surgeons, thrombosis experts and medical oncologists who manage patients with abdominopelvic cancers at 1 large Canadian academic centre were invited to complete the survey between January and April 2019. Results: Of the 57 physicians invited, 42 (74%) completed the survey, including 27 surgeons (response rate 79%), 9 thrombosis experts (response rate 75%) and 6 medical oncologists (response rate 55%). Most surgeons (22 [82%]) reported using mechanical thromboprophylaxis, whereas only 1 thrombosis expert (11%) recommended mechanical thromboprophylaxis. There was substantial variability in the timing of the initial dose of thromboprophylaxis, with 9/10 urologists (90%) and all 7 general surgeons giving the first dose intraoperatively, and three-quarters of thoracic surgeons (3/4 [75%]), gynecologists (3/4 [75%]) and thrombosis experts (7/9 [78%]) starting thromboprophylaxis after surgery. All medical oncologists believed chemotherapy increases the risk of venous thromboembolism, but 4 (67%) reported that they do not routinely prescribe thromboprophylaxis owing to bleeding concerns. Most respondents (35/38 [92%]) felt there was a need for more research on thromboprophylaxis and indicated willingness to participate in future clinical trials. Conclusion: Variability exists in contemporary thromboprophylaxis practice patterns among physicians treating patients with abdominopelvic cancer. Future research is needed to standardize care and improve outcomes for patients.

Contexte: On manque de données de qualité élevée sur la thromboprophylaxie chez les patients traités en chirurgie pour un cancer abdomino-pelvien. Nous avons sondé des médecins traitant ces patients afin de déterminer les tendances actuelles relatives à cette pratique et pour cerner les besoins en recherche. Méthodes: Nous avons créé un sondage en ligne sur la thromboprophylaxie, comprenant des questions sur le type utilisé, le moment d'administration de la dose initiale, le recours durant la chimiothérapie, l'utilisation prolongée et les domaines de recherche à explorer. Les questions ont été validées par des experts de contenu externes, qui ont veillé à ce qu'elles soient appropriées et pertinentes. Des chirurgiens, des experts en thrombose et des oncologues qui s'occupent de patients atteints de cancers abdomino-pelviens dans un grand centre hospitalier universitaire canadien ont été invités à remplir le sondage entrer janvier et avril 2019. Résultats: Des 57 médecins sollicités, 42 (74%) ont répondu au sondage, dont 27 chirurgiens (taux de réponse de 79%), 9 experts en thrombose (taux de réponse de 75 %) et 6 oncologues (taux de réponse de 55 %). La majorité des chirurgiens (22 [82 %]) recouraient à la thromboprophylaxie mécanique, alors qu'un seul expert en thrombose (11 %) recommandait cette pratique. Le moment d'administration de la dose initiale variait considérablement: 9 urologues sur 10 (90%) et chacun des 7 chirurgiens généralistes administraient la première dose durant l'opération, alors que les trois quarts des chirurgiens thoraciques (3/4 [75%]), des gynécologues (3/4 [75%]) et des experts en thrombose (7/9 [78%]) commençaient la thromboprophylaxie après l'intervention. Tous les oncologues étaient d'avis que la chimiothérapie augmentait le risque de thromboembolie veineuse, mais 4 (67%) ont indiqué qu'ils ne prescrivaient pas d'emblée de thromboprophylaxie en raison des risques de saignements. La plupart des répondants (35/38 [92%]) considéraient qu'il faudrait étudier davantage la thromboprophylaxie et ont indiqué leur volonté de participer à d'éventuels essais cliniques. Conclusion: À l'heure actuelle, les pratiques liées à la thromboprophylaxie varient chez les médecins traitant des patients atteints de cancers abdomino-pelviens. Il faudra mener d'autres études pour normaliser la prestation des soins et améliorer les résultats pour les patients.

Development and Acceptability Testing of a Patient Decision Aid for Urinary Diversion with Radical Cystectomy.

PURPOSE: The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid. RESULTS: Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria. CONCLUSIONS: We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

Development and Implementation of a Continuing Medical Education Program in Canada: Knowledge Translation for Renal Cell Carcinoma (KT4RCC).

An in-person multidisciplinary continuing medical education (CME) program was designed to address previously identified knowledge gaps regarding quality indicators of care in kidney cancer. The objective of this study was to develop a CME program and determine if the program was effective for improving participant knowledge. CME programs for clinicians were delivered by local experts (uro-oncologist and medical oncologist) in four Canadian cities. Participants completed knowledge assessment tests pre-CME, immediately post-CME, and 3-month post-CME. Test questions were related to topics covered in the CME program including prognostic factors for advanced disease, surgery for advanced disease, indications for hereditary screening, systemic therapy, and management of small renal masses. Fifty-two participants attended the CME program and completed the pre- and immediate post-CME tests. Participants attended in Ottawa (14; 27%), Toronto (13; 25%), Québec City (18; 35%), and Montréal (7; 13%) and were staff urologists (21; 40%), staff medical oncologists (9; 17%), fellows (5; 10%), residents (16; 31%), and oncology nurses (1; 2%). The mean pre-CME test score was 61% and the mean post-CME test score was 70% (p = 0.003). Twenty-one participants (40%) completed the 3-month post-CME test. Of those that completed the post-test, scores remained 10% higher than the pre-test (p value 0.01). Variability in test scores was observed across sites and between French and English test versions. Urologists had the largest specialty-specific increase in knowledge at 13.8% (SD 24.2, p value 0.02). The kidney cancer CME program was moderately effective in improving provider knowledge regarding quality indicators of kidney cancer care. These findings support continued use of this CME program at other sites.

The Risks and Benefits of Cavernous Neurovascular Bundle Sparing during Radical Prostatectomy: A Systematic Review and Meta-Analysis.

PURPOSE: We summarize published data on associations between cavernous neurovascular bundle preservation (nerve sparing) during prostatectomy and positive surgical margins, erectile function, urinary function and other patient reported outcomes. MATERIALS AND METHODS: A systematic literature search of MEDLINE®, Embase® and Cochrane Reviews databases was performed for interventional or observational studies published between 2000 and 2014. English language articles that compared clinical outcomes of patients undergoing nerve sparing and nonnerve sparing radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk estimates for positive surgical margins, erectile dysfunction and urinary incontinence in nerve sparing and nonnerve sparing groups. Sensitivity analyses compared outcomes among unilateral and bilateral nerve sparing vs nonnerve sparing groups. RESULTS: Of the 1,883 articles identified, 124 studies (73,448 patients) were included in the analysis. Nerve sparing did not increase the risk of positive surgical margins in patients with pT2 (RR 0.92, 95% CI 0.75-1.13) or pT3 disease (RR 0.83, 95% CI 0.71-0.96), potentially due to appropriate patient selection. The risk of incontinence was lower in nerve sparing cases (RR 0.75, 95% CI 0.65-0.85 and RR 0.61, 95% CI 0.44-0.84) at 3 and 12 months, respectively. The relative risk of erectile dysfunction with nerve sparing was 0.77 (95% CI 0.70-0.85) at 3 months and 0.53 (95% CI 0.39-0.71) at 12 months. Subgroup analyses of unilateral and bilateral nerve sparing approaches demonstrated similar results. CONCLUSIONS: Among cohort studies nerve sparing was not associated with worse cancer outcomes. Nerve sparing is associated with better urinary and erectile function. These results should be interpreted with caution given the potential for selection bias and unadjusted confounding factors.

Suburothelial and extrinsic lesions of the urinary bladder: radiologic and pathologic features with emphasis on MR imaging.

OBJECTIVE: The purpose of this article is to present a contemporary review of the imaging appearance of diseases which affect the deeper layers of the urinary bladder, including both suburothelial and extrinsic pathologies, using radiologic-pathologic correlation. CONCLUSION: Compared to the more common urothelial lesions, at cystoscopy, suburothelial and extrinsic diseases of the urinary bladder wall often have a non-specific appearance or may be occult. Cross-sectional imaging, in particular MRI, plays an integral role in diagnosis. Mesenchymal tumors have distinct imaging features on MRI. Leiomyomas are characteristically low signal intensity on T2-weighted (T2W) imaging and progressively enhance. Lipomas and lipomatous hypertrophy are diagnosed by the presence of macroscopic fat. Neurofibromas, hemangiomas, and paragangliomas are hyperintense on T2W sequences and hypervascular. Reactive lesions occur in the setting of chronic inflammation and include: nephrogenic adenoma, cystitis cystica, and cystitis glandularis. Imaging findings are commonly non-specific; however, a mass with internal cystic spaces in association with pelvic lipomatosis is suggestive of cystitis glandularis. Urachal anomalies may be complicated by infection or malignancy. Urachal mucinous adenocarcinoma has a poor prognosis and may present as a T2-hyperintense suburothelial/extrinsic mass centered in the bladder dome. Other diseases may extrinsically involve the urinary bladder by hematogenous and peritoneal spread, including infection, endometriosis, and malignancy. A familiarity with suburothelial and extrinsic pathologies of the urinary bladder is critical for the radiologist, who may be the first to suggest these diagnoses.

Progression to detrusor muscle invasion during urothelial carcinoma surveillance is associated with poor prognosis.

OBJECTIVE: To evaluate survival in patients after radical cystectomy (RC) who presented with non-muscle-invasive urothelial carcinoma and progressed to muscle invasion during surveillance. Our secondary objective was to evaluate the association between clinical factors before RC and survival. PATIENTS AND METHODS: In all, 981 consecutive Mayo Clinic RC patients without a history of radiation or systemic chemotherapy were reviewed. Of these, 190 had RC after they progressed from non-muscle invasive disease to muscle invasion (progressed to ≥pT2). These patients were compared to 310 patients who had RC before muscle invasion (≤pT1), and 481 patients who had muscle invasion at initial presentation (presented with ≥pT2). Survival estimates were generated using the Kaplan-Meier method and compared using the log-rank test, while adjusted analyses were performed using Cox proportional hazard regression models. RESULTS: Patients who progressed to muscle invasion on surveillance had a higher risk of death than patients who initially presented with muscle invasion (overall survival hazard ratio [HR] 1.3; 95% confidence interval [CI] 1.0, 1.5). The estimated 5-year cancer-specific survival was 85.4% for patients presenting with ≤pT1, 52.9% for patients who progressed to ≥pT2, and 62.4% for patients who presented with ≥pT2 (P < 0.001). The corresponding 5-year overall survival rates were 70.0%, 42.1%, and 49.5% (P < 0.001). Of the patients who initially presented with non-muscle-invasive disease, progression to muscle invasion was associated with increased risk of cancer-specific death (adjusted HR 2.38; 95% CI 1.6, 3.5). Lack of information about patients who presented without muscle invasion and never received RC is the major limitation of this study. CONCLUSIONS: Despite close surveillance, many patients who progress to muscle invasion will die from bladder cancer. Patients who progress to muscle invasion on surveillance seem to have particularly aggressive disease and may benefit from multimodal treatments.

Impact of concomitant carcinoma in situ on upstaging and outcome following radical cystectomy for bladder cancer.

PURPOSE: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. METHODS: We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. RESULTS: In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. CONCLUSION: These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.

How Surgeons Think to Avoid Error: A Case Study of the Neurovascular Bundle Sparing During a Robotic Prostatectomy.

OBJECTIVE: To illustrate how experts efficiently navigate a "slowing down moment" to obtain optimal surgical outcomes using the neurovascular bundle sparing during a robotic prostatectomy as a case study. DESIGN: A series of semistructured interviews with four expert uro-oncologists were completed using a cognitive task analysis methodology. Cognitive task analysis, CTA, refers to the interview and extraction of a general body of knowledge. Each interview participant completed four 1 to 2-hour semistructured CTA interviews. The interview data were then deconstructed, coded, and analyzed using a grounded theory analysis to produce a CTA-grid for a robotic prostatectomy for each surgeon, with headings of: surgical steps, simplification maneuvers, visual cues, error/complication recognition, and error/complication management and avoidance. SETTING: The study took place at an academic teaching hospital located in an urban center in Canada. PARTICIPANTS: Four expert uro-oncologists participated in the study. RESULTS: Visual cues, landmarks, common pitfalls, and technique were identified as the 4 key components of the decision-making happening during a slowing down moment in the neurovascular bundle sparing during a robotic prostatectomy. CONCLUSION: The data obtained from the CTA is novel information identifying patterns and cues that expert surgeons use to inform their surgical decision-making and avoid errors. This decision-making knowledge of visual cues, landmarks, common pitfalls and techniques is also generalizable for other surgical subspecialties. Surgeon educators, surgical teaching programs and trainees looking to improve their decision-making skills could use these components to guide their educational strategies.

Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.

INTRODUCTION: Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice. METHODS: Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients newly diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation. RESULTS: A total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. From 2014-2017, docetaxel was the most commonly used approach, although it was supplanted by abiraterone acetate, apalutamide and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). Intensification increased for patients living in rural areas and with higher disease burden in 2018+ compared to 2014-2017. CONCLUSIONS: There has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Tranexamic Acid During Radical Cystectomy: A Randomized Clinical Trial.

Importance: Among cancer surgeries, patients requiring open radical cystectomy have the highest risk of red blood cell (RBC) transfusion. Prophylactic tranexamic acid (TXA) reduces blood loss during cardiac and orthopedic surgery, and it is possible that similar effects of TXA would be observed during radical cystectomy. Objective: To determine whether TXA, administered before incision and for the duration of radical cystectomy, reduced the number of RBC transfusions received by patients up to 30 days after surgery. Design, Setting, and Participants: The Tranexamic Acid During Cystectomy Trial (TACT) was a double-blind, placebo-controlled, randomized clinical trial with enrollment between June 2013 and January 2021. This multicenter trial was conducted in 10 academic centers. A consecutive sample of patients was eligible if the patients had a planned open radical cystectomy for the treatment of bladder cancer. Intervention: Before incision, patients in the intervention arm received a loading dose of intravenous TXA, 10 mg/kg, followed by a maintenance infusion of 5 mg/kg per hour for the duration of the surgery. In the control arm, patients received indistinguishable matching placebo. Main Outcomes and Measures: The primary outcome was receipt of RBC transfusion up to 30 days after surgery. Results: A total of 386 patients were assessed for eligibility, and 33 did not meet eligibility. Of 353 randomized patients (median [IQR] age, 69 [62-75] years; 263 male [74.5%]), 344 were included in the intention-to-treat analysis. RBC transfusion up to 30 days occurred in 64 of 173 patients (37.0%) in the TXA group and 64 of 171 patients (37.4%) in the placebo group (relative risk, 0.99; 95% CI, 0.83-1.18). There were no differences in secondary outcomes among the TXA group vs placebo group including mean (SD) number of RBC units transfused (0.9 [1.5] U vs 1.1 [1.8] U; P = .43), estimated blood loss (927 [733] mL vs 963 [624] mL; P = .52), intraoperative transfusion (28.3% [49 of 173] vs 24.0% [41 of 171]; P = .08), or venous thromboembolic events (3.5% [6 of 173] vs 2.9% [5 of 171]; P = .57). Non-transfusion-related adverse events were similar between groups. Conclusions and Relevance: Results of this randomized clinical trial reveal that TXA did not reduce blood transfusion in patients undergoing open radical cystectomy for bladder cancer. Based on this trial, routine use of TXA during open radical cystectomy is not recommended. Trial Registration: ClinicalTrials.gov Identifier: NCT01869413.

Comparison of oncological outcomes for open and laparoscopic radical nephroureterectomy: results from the Canadian Upper Tract Collaboration.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?Open radical nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma (UTUC). However, over the past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established. We found that surgical approach was not independently associated with overall or disease-specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence-free survival (RFS). To our knowledge, this is the first large, multi-institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU. OBJECTIVE: To examine the association between surgical approach for radical nephroureterectomy (RNU) and clinical outcomes in a large, multi-institutional cohort, as there are limited data comparing the oncological efficacy of open RNU (ORNU) and laparoscopic RNU (LRNU) for upper urinary tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Institutional RNU databases containing detailed information on patients with UTUC treated between 1994 and 2009 were obtained from 10 academic centres in Canada. Data were collected on 1029 patients and combined into a relational database formatted with patient characteristics, pathological characteristics, and survival status. Surgical approach was classified as ORNU (n = 403) or LRNU (n = 446). The clinical outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression analysis were used to analyse survival data. RESULTS: Data were evaluable for 849 of 1029 (82.5%) patients. The median (interquartile range) follow-up duration was 2.2 (0.6-5.0) years. The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU groups; however, there was a trend toward an improved predicted 5-year RFS rate in the ORNU group (43% vs 33%, log-rank P = 0.06). Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.63-1.27, P = 0.52) or DSS (HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was a trend toward an independent association between surgical approach and RFS (HR 1.24, 95% CI 0.98-1.57, P = 0.08). CONCLUSION: Surgical approach was not independently associated with OS or DSS but there was a trend toward an independent association between LRNU and poorer RFS. Further prospective evaluation is needed.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Yield of second-round MRI targeted ultrasound-guided fusion prostate biopsy after initial first-round targeted biopsy.

INTRODUCTION: We aimed to determine the yield of second-round magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy and factors that may predict eventual clinically significant (CS) prostate cancer (PCa) diagnosis. METHODS: From 2013 to 2021, 85 men underwent second-round MRI-US fusion biopsy of 92 lesions (47.8% [44/92] peripheral zone and 52.2% [48/92] transition zone). Patient age, prostate-specific antigen (PSA), PSA density (PSAD), size/location of lesions, ADC value, Prostate Imaging-Reporting and Data System (PI-RADS), and PRECISE scores were recorded and compared to histopathological diagnosis (International Society of Urological Pathology [ISUP] grade-group 1 PCa, CS PCa=ISUP grade group ≥2 PCa) using logistic regression. RESULTS: Mean patient age, PSA, and PSAD were 64±7 years, 8.5±7.0 ng/ml, and 0.17±0.11, respectively. Results from first-round targeted biopsy were 63% (58/92) negative and 37% (34/92) clinically insignificant (grade group 1) PCa. Overall, second-round targeted biopsy identified 25% (23/92) CS PCa (grade group 2, n=19; grade group 3, n=4). Considering only lesions with initial negative targeted-biopsy results (n=58), 21% (12/58; grade group 2, n=8; grade group 3, n=4) CS PCa and 13 grade group 1 PCa were diagnosed at second-round biopsy. There was no difference in PSA (p=0.564), size (p=0.595), location (p=0.293), or PI-RADS score (p=0.342) of lesions by eventual CS PCa diagnosis. PSAD (0.2±1.4 vs. 0.16±0.10, p=0.167), ADC (0.748±0.199 vs. 0.833±0.257, p=0.151), and PRECISE score (p<0.01) showed a trend towards association or association with eventual CS PCa diagnosis. CONCLUSIONS: Repeat second-round targeted MRI-US fusion biopsy yielded CS PCa diagnosis in the targeted biopsy specimen in approximately 20% of patients in our study. PRECISE score may be a useful marker to help predict which patients require second-round biopsy.

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience.

UNLABELLED: Study Type - Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease. OBJECTIVES: • To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC). • To establish appropriate surveillance protocols. PATIENTS AND METHODS: • We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres. • Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study. RESULTS: • A total of 825 patients (43.6%) developed recurrence. • According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant. • The median (range) time to recurrence for the entire population was 10.1 (1-192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively. • According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5-yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1-72 months) than ≥pT3N0 tumours (10 months, range 1-70 months) or ≤pT2N0 tumours (14 months, range 1-192 months, P < 0.001). CONCLUSIONS: • Differences in recurrence patterns after RC suggest the need for varied follow-up protocols for each group. • We propose a stage-based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over-investigation.

Radical cystectomy for clinically muscle invasive bladder cancer: does prior non-invasive disease affect clinical outcomes?

PURPOSE: To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma. MATERIALS AND METHODS: Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N = 365) and (Group 2) patients with clinical muscle invasive cancer de novo (N = 785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality. RESULTS: Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7 years, and 79.7 and 79.5%, respectively (P = 0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P = 0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P < 0.0001), positive lymph nodes were 20.1 and 28.8% (P = 0.002), and lymphovascular invasion was 31.7 and 46.2% (P = 0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P = 0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5 years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10 years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P = 0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P = 0.0002). CONCLUSION: Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo.