Publications by authors named "Alan So"

172 Publications

The increasing use of renal tumor biopsy amongst Canadian urologists: When is biopsy most utilized?

Urol Oncol 2021 Jun 26. Epub 2021 Jun 26.

Department of Urology, Centre Hospitalier Universitaire de Sherbrooke and Centre de Recherche du CHUS, Sherbrooke, QC, Canada. Electronic address:

Introduction: The role of renal tumor biopsy (RTB) in the management of small renal masses (SRMs) is progressively being recognized as a tool to decrease overtreatment. While an increasing number of studies assessing its role in diagnostics are becoming available, RTB remains variably used amongst urologists. Many patient-, tumor-, and institution-related factors may influence urologists on whether to perform a RTB to help guide management.

Objective: We aimed at identifying factors associated with the use of RTB for localized SRMs within a number of centers contributing data to the Canadian Kidney Cancer information system.

Material And Methods: We identified 3,838 patients diagnosed with a localized SRM (≤4 cm) between January 2011 and December 2018. Patients were stratified based on whether a RTB was performed prior to the primary therapeutic intervention. Factors associated with use of RTB were assessed using univariable and multivariable logistic regression models.

Results: A total of 993 patients (25.9%) underwent an RTB. There was an overall increase in RTB use over time (P < 0.001), with patients diagnosed between 2015 and 2018 undergoing more RTB than patients diagnosed between 2011 and 2014 (29.8% vs. 22.2%, respectively; P < 0.001). Patients managed in centers with the highest patient-volume had RTB more frequently than patients managed in low-volume centers. On multivariable analysis, increasing year of diagnosis was significantly associated with more RTB use. Patients treated with surgery underwent RTB statistically less often than patients undergoing thermal ablation (P < 0.001) or managed with active surveillance (P < 0.001). Larger SRMs were associated with more RTB use in patients on active surveillance (P = 0.009), but with less RTB in patients undergoing surgery (P = 0.045).

Conclusion: This large multicenter cohort study reveals an increasing adoption and overall use of RTB amongst Canadian urologists. Patients managed in high-volume centers and those undergoing non-surgical management were associated with greater use of RTB. Tumor size was also associated with RTB use. This study highlights the influence that physician perceptions and clinical factors may have in the decision to use RTB prior to initiating a therapeutic approach.
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http://dx.doi.org/10.1016/j.urolonc.2021.05.026DOI Listing
June 2021

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes From the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort.

Urology 2021 Jun 12. Epub 2021 Jun 12.

Urology Division, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

Objective: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low.

Methods: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis.

Results: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48).

Conclusion: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.
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http://dx.doi.org/10.1016/j.urology.2021.05.053DOI Listing
June 2021

Results from a Canadian consensus forum of key controversial areas in the management of advanced prostate cancer: Recommendations for Canadian healthcare providers.

Can Urol Assoc J 2021 Jun 8. Epub 2021 Jun 8.

Medical Affairs, Janssen Inc, Toronto, ON, Canada.

Introduction: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) have created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment.

Methods: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions and the analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥ 75% for 'consensus agreement', > 50% for "near-consensus", and ≤ 50% for "no consensus".

Results: The panel was comprised of 29 PCa experts including urologists (n=12), medical oncologists (n= 12), and radiation oncologists (n= 5). Voting took place for 65 pre-determined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling.

Conclusion: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.
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http://dx.doi.org/10.5489/cuaj.7347DOI Listing
June 2021

Lymph node dissection during radical nephrectomy: A Canadian multi-institutional analysis.

Urol Oncol 2021 Jun 27;39(6):371.e17-371.e25. Epub 2021 Mar 27.

The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Objectives: To determine the association between lymph node dissection (LND) at the time of radical nephrectomy and survival in a large, multi-institutional cohort using a propensity score matching design.

Subjects And Methods: The Canadian Kidney Cancer information system was used to identify patients undergoing radical nephrectomy for nonmetastatic renal cell carcinoma. Associations between LND with overall survival , recurrence free survival and cancer specific survival were determined using various propensity score techniques in the overall cohort and in patients with varying probabilities of pN1. Cox models were used to determine association of lymph node removed with outcomes.

Results: Of the 2,699 eligible patients, 812 (30%) underwent LND. Of the LND patients, 88 (10.8%) had nodal metastases. There was no association between LND and improved overall survival, recurrence free survival or cancer specific survival using various propensity score techniques (stratification by propensity score quintile, matched pairs, inverse treatment probability weighting and adjusted for propensity score quintile). There was no association between LND and a therapeutic benefit in patients with increased threshold probabilities of nodal metastases. Increased number of lymph nodes removed was not associated with improved survival outcomes.

Conclusions: LND at the time of radical nephrectomy for renal cell carcinoma is not associated with improved outcomes. There was no benefit in patients at high risk for nodal metastases, and the number of nodes removed did not correlate with survival. Further studies are needed to determine which high risk patients may benefit from LND.
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http://dx.doi.org/10.1016/j.urolonc.2021.02.025DOI Listing
June 2021

Comparing Perspectives of Canadian Men Diagnosed With Prostate Cancer and Health Care Professionals About Active Surveillance.

J Patient Exp 2020 Dec 11;7(6):1122-1129. Epub 2020 Jun 11.

Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal, Quebec, Canada.

Active surveillance (AS) has gained acceptance as a primary management approach for patients diagnosed with low-risk prostate cancer (PC). In this qualitative study, we compared perspectives between patients and health care professionals (HCP) to identify what may contribute to patient-provider discordance, influence patient decision-making, and interfere with the uptake of AS. We performed a systematic comparison of perspectives about AS reported from focus groups with men eligible for AS (7 groups, N = 52) and HCP (5 groups, N = 48) who engaged in conversations about AS with patient. We used conventional content analysis to scrutinize separately focus group transcripts and reached a consensus on similar or divergent viewpoints between them. Patients and clinicians agreed that AS was appropriate for low grade PC and understood the low-risk nature of the disease. They shared the perspective that disease status was a critical factor to pursue or discontinue AS. However, men expressed a greater emphasis on quality of life in their decisions related to AS. Patients and clinicians differed in their perspectives on the clarity, availability, and volume of information needed and offered; clinicians acknowledged variations between HCP when presenting AS, while patients were often compelled to seek additional information beyond what was provided by physicians and experienced difficulty in finding or interpreting information applicable to their situation. A greater understanding of discordant perspectives about AS between patients and HCP can help improve patient engagement and education, inform development of knowledge-based tools or aids for decision-making, and identify areas that require standardization across the clinical practice.
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http://dx.doi.org/10.1177/2374373520932735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786672PMC
December 2020

Determining generalizability of the Canadian Kidney Cancer information system (CKCis) to the entire Canadian kidney cancer population.

Can Urol Assoc J 2020 Oct;14(10):E499-E506

Department of Medicine and Urology, Dalhousie University, Halifax, NS, Canada.

Introduction: The Canadian Kidney Cancer information system (CKCis) has prospectively collected data on patients with renal tumors since January 1, 2011 from 16 sites within 14 academic centers in six provinces. Canadian kidney cancer experts have used CKCis data to address several research questions. The goal of this study was to determine if the CKCis cohort is representative of the entire Canadian kidney cancer population, specifically regarding demographic and geographic distributions.

Methods: The CKCis prospective cohort was analyzed up to December 31, 2018. Baseline demographics and tumor characteristics were analyzed, including location of patients' residence at the time of CKCis entry. Geographic data is presented by province, rural vs. urban via postal code information (2 digit=0) and by Canadian urban boundary files. To determine the proportion of renal cell carcinoma (RCC) patients that CKCis captures, CKCis accruals were compared to projected Canadian Cancer Society RCC incidence in 2016-2017 and the incidence from the 2016 Canadian Cancer Registry. To determine if the CKCis baseline data is representative, it was compared to registry data and other published data when registry data was not available.

Results: This CKCis cohort includes 10 298 eligible patients: 66.6% male, median age 62.6 years; 14.6% had metastatic disease at the time of diagnosis and 70.4% had clear-cell carcinomas. The CKCis cohort captures about 1250 patients per year, which represents approximately 20% of the total kidney cancer incidence. The proportion of patients captured per province did vary from 13-43%. Rural patients make up 17% of patients, with some baseline differences between rural and urban patients. There appears to be no major differences between CKCis patient demographics and disease characteristics compared to national data sources. Canadian heat maps detailing patient location are presented.

Conclusions: CKCis contains prospective data on >10 000 Canadian kidney cancer patients, making it a valuable resource for kidney cancer research. The baseline demographic and geographic data do appear to include a broad cross-section of patients and seem to be highly representative of the Canadian kidney cancer population. Moving forward, future projects will include determining if CKCis cancer outcomes are also representative of the entire Canadian kidney cancer population and studying variations across provinces and within rural vs. urban areas.
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http://dx.doi.org/10.5489/cuaj.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716824PMC
October 2020

Canadian Urological Association best practice report: Diagnosis and management of sporadic angiomyolipomas.

Can Urol Assoc J 2020 Nov;14(11):E527-E536

Division of Urology, Department of Surgery, Trillium Health Partners, Mississauga, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.6942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673831PMC
November 2020

Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors.

Eur Urol 2021 01 4;79(1):16-19. Epub 2020 Nov 4.

Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease.
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http://dx.doi.org/10.1016/j.eururo.2020.10.024DOI Listing
January 2021

Prognostic impact of paraneoplastic syndromes on patients with non-metastatic renal cell carcinoma undergoing surgery: Results from Canadian Kidney Cancer information system.

Can Urol Assoc J 2021 Apr;15(4):132-137

Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy.

Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis.

Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p<0.05). Kaplan-Meier five-year estimated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were significantly worse in patients with PNS (63.7%, 84.3%, and 79.6%, respectively, for patients with PNS vs. 73.9%, 90.8%, and 90.1%, respectively, for patients without PNS, all p<0.005). On univariable analysis, presence of PNS increased risk of recurrence (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.48-1.90, p<0.0001) and cancer-related death (HR 1.85, 95% CI 1.34-2.54, p=0.0002). Adjusting for known prognostic factors, PNS was not associated with recurrence or survival.

Conclusions: In non-metastatic RCC patients undergoing surgery, presence of PNS is associated with older age, higher Charlson comorbidity index score, advanced tumor stage, and aggressive tumor histology. Following surgery, baseline PNS is not strongly independently associated with recurrence or death.
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http://dx.doi.org/10.5489/cuaj.6833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021432PMC
April 2021

Real-world management of advanced prostate cancer: A description of management practices of community-based physicians and prostate cancer specialists.

Can Urol Assoc J 2021 Feb;15(2):E90-E96

Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada.

Introduction: The Canadian Genitourinary Research Consortium (GURC) conducted a consensus development conference leading to 31 recommendations. Using the GURC consensus development questionnaire, we conducted a survey to measure the corresponding community-based practices on the management of metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).

Methods: An 87-item online questionnaire was sent to 600 community urologists and oncologists involved in the treatment of prostate cancer.

Results: Seventy-two community physicians responded to the survey. Of note, 50% community physicians indicated they would treat nmCRPC with agents approved for this indication if advanced imaging showed metastases. Radiation to the prostate for low-volume mCSPC was identified as a treatment practice by 27% of community physicians, and 35% indicated docetaxel as the next line of treatment after use of apalutamide. Use of genetic testing was reported in 36% of community physicians for newly diagnosed metastatic prostate cancer.

Conclusions: There are several areas of community-based management of advanced prostate cancer that could represent potential areas for education, practice tools, and future research.
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http://dx.doi.org/10.5489/cuaj.6779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864716PMC
February 2021

Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience.

Urol Oncol 2020 10 7;38(10):799.e1-799.e10. Epub 2020 Aug 7.

Faculty of Medicine, McGill University, Montreal, QC, Canada.

Background: Surgical resection of metastasis can be integrated in the management of metastatic renal cell carcinoma (mRCC) as it can contribute to delay disease progression and improve survival.

Objective: This study assessed the impact of complete metastasectomy in mRCC patients using real-world pan-Canadian data.

Design, Setting And Participants: The Canadian Kidney Cancer information system (CKCis) database was used to select patients who were diagnosed with mRCC between January 2011 and April 2019. To minimize selection bias, each patient having received a complete metastasectomy was matched with up to 4 patients not treated with metastasectomy.

Outcome Measurements And Statistical Analysis: Overall survival (OS) was calculated from the date of metastasectomy or selection, to death from any cause. A Cox proportional hazards model was used to assess the impact of the metastasectomy while adjusting for potential confounding variables.

Results: A total of 229 patients undergoing complete metastasectomy were matched with 803 patients not treated with metastasectomy. After matching, baseline characteristics were well balanced between groups. After 12 months, the proportion of patients that were still alive was 96.0% and 89.8% in the complete metastasectomy and its matched group, respectively; the 5-year OS were 63.2% and 51.4%, respectively. Multivariate analysis performed in the matched cohort revealed that patients who underwent complete metastasectomy had a lower risk of mortality compared to patients who did not undergo metastasectomy (hazard ratio: 0.41, 95% confidence interval:0.27-0.63).

Conclusion: Our study found that patients who underwent complete metastasectomy have a longer overall survival and a longer time to initiation of targeted therapy compared to patients not receiving metastasectomy. These findings should support aggressive resection of metastasis in selected patients.
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http://dx.doi.org/10.1016/j.urolonc.2020.07.021DOI Listing
October 2020

Defining postoperative ileus and associated risk factors in patients undergoing radical cystectomy with an Enhanced Recovery After Surgery (ERAS) program.

Can Urol Assoc J 2021 Feb;15(2):33-39

Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.

Introduction: Postoperative ileus (POI) is a common complication of radical cystectomy (RC), occurring in 1.6-23.5% of cases. It is defined heterogeneously in the literature. POI increases hospital length of stay and postoperative morbidity. Factors such as age, epidural use, length of procedure, and blood loss may impact POI. In this study, we aimed to evaluate risk factors that contribute to POI in a cohort of patients managed with a comprehensive Enhanced Recovery After Surgery (ERAS) protocol.

Methods: A retrospective review of consecutive patients who underwent RC from March 2015 to December 2016 at Vancouver General Hospital was performed. POI was defined a priori as insertion of nasogastric tube for nausea or vomiting, or failure to advance to a solid diet by the seventh postoperative day. To illustrate heterogeneity in previous studies, we also evaluated POI using other previously reported definitions in the RC literature. The influence of potential risk factors for POI, including patient comorbidities, American Society of Anesthesiologists score, gender, age, prior abdominal surgery or radiation, length of operation, diversion type, extent of lymph node dissection, removal date of analgesic catheter, blood loss, and fluid administration volume was analyzed.

Results: Thirty-six (27%) of 136 patients developed POI. Using other previously reported definitions for POI, the incidence ranged from <1-51%. Node-positive status and age at surgery were associated with POI on univariate analysis but not multivariable analysis.

Conclusions: A large range of POI incidence was observed using previously published definitions of POI. We advocate for a standardized definition of POI when evaluating RC outcomes. POI occurs frequently even with a comprehensive ERAS protocol, suggesting that additional measures are needed to reduce the rate of POI.
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http://dx.doi.org/10.5489/cuaj.6546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864711PMC
February 2021

Does renal tumor biopsies for small renal carcinoma increase the risk of upstaging on final surgery pathology report and the risk of recurrence?

Urol Oncol 2020 10 18;38(10):798.e9-798.e16. Epub 2020 Jul 18.

Urology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:

Background: Renal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes.

Objectives: To evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence.

Design, Setting And Participants: The Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019.

Intervention: RTB prior to nephrectomy or nephrectomy without biopsy.

Outcomes Measurements And Statistical Analysis: Upstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence.

Results And Limitations: The cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61-1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57-1.89). The main limitation is that the study is underpowered to detect small differences between groups.

Conclusions: In this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment.

Patient Summary: Recent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.
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http://dx.doi.org/10.1016/j.urolonc.2020.06.001DOI Listing
October 2020

Impact of Time to Surgery and Surgical Delay on Oncologic Outcomes for Renal Cell Carcinoma.

J Urol 2021 Jan 2;205(1):78-85. Epub 2020 Jul 2.

Section of Urology, University of Manitoba, Winnipeg, Manitoba, Canada.

Purpose: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma.

Materials And Methods: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models.

Results: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death.

Conclusions: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.
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http://dx.doi.org/10.1097/JU.0000000000001230DOI Listing
January 2021

Aquablation for benign prostatic hyperplasia in large prostates (80-150 cc): 2-year results.

Can J Urol 2020 04;27(2):10147-10153

University of Southern California, Institute of Urology, Los Angeles, California, USA.

Introduction: To report 2-year safety and effectiveness of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia (BPH) and large-volume 80-150 cc prostates.

Materials And Methods: Between September-December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volumes of 80-150 cc underwent an ultrasound-guided robotically executed Aquablation procedure in a prospective multicenter international clinical trial (WATER II). Baseline, procedural and follow up parameters were recorded at baseline and scheduled postoperative visits. Herein we report 2-year safety and efficacy for this cohort.

Results: Mean prostate volume was 107 cc (range 80-150 cc). Mean IPSS improved from 23.2 at baseline to 5.8 at 2 years (17-point improvement, p < .0001). Mean IPSS quality of life improved from 4.6 at baseline to 1.1 at 2 years (p < .0001). Maximum urinary flow increased from 8.7 to 18.2 cc/sec. Two subjects underwent a repeat procedure for BPH symptoms over the 2-year follow up period. By 2 years or study exit, all but 2 of 74 subjects stopped taking alpha blockers. Similarly, all but 4 of 32 subjects stopped taking 5α-reductase inhibitors.

Conclusions: Two-year prospective multicenter follow up demonstrated that the Aquablation procedure is safe and effective in the treatment of men with LUTS due to BPH and prostates 80-150 cc with durable treatment efficacy, acceptable safety profile and a low retreatment rate. ClinicalTrials.gov number, NCT03123250.
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April 2020

Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer.

NPJ Genom Med 2020 23;5:12. Epub 2020 Mar 23.

1Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC Canada.

Germline pathogenic variants in the BRCA1-associated protein-1 () gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift variant, and as expected, immunostaining validated the loss of BAP1 protein in patient-derived tumor specimens. Together, these data provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline mutations, our understanding of the BAP1 TPDS continues to evolve, and may affect future screening and surveillance guidelines.
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http://dx.doi.org/10.1038/s41525-020-0121-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089973PMC
March 2020

Metastatic Renal Cell Carcinoma to the Testis: A Clinicopathologic Analysis of Five Cases.

Case Rep Pathol 2020 2;2020:9394680. Epub 2020 Mar 2.

Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada.

The testicular spread of renal cell carcinoma is extremely rare. Five cases of renal cell carcinoma metastatic to the testis are described. The patients ranged from 45 to 81 years of age. Four of the five patients had known renal cell carcinoma. The time intervals between the partial and radical nephrectomies for the primary kidney tumors and the occurrence of testicular metastases ranged from 29 to 34 months. In one patient, the testicular mass was the initial presentation leading to a diagnosis of renal cell carcinoma. There were three ipsilateral metastases, one contralateral metastasis, and one bilateral metastasis. The metastatic deposits ranged in size from 2.0 to 5.7 cm. One case had multiple metastatic tumor nodules. All of the metastatic tumors had clear cell histological features, microscopically concordant with the primary renal cell carcinoma subtype. Three patients died of the disease 17 to 42 months after orchiectomy. One patient is alive with additional metastatic lesions 13 months after orchiectomy. One patient had been free of disease at 87 months after orchiectomy but is now on targeted therapy for an additional metastasis at 93 months after orchiectomy. To date, this report is one of the largest single series of patients with renal cell carcinoma metastatic to the testis, and it has the longest follow-up and survival among all the reported cases.
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http://dx.doi.org/10.1155/2020/9394680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073490PMC
March 2020

Plasma Circulating Tumor DNA and Clonal Hematopoiesis in Metastatic Renal Cell Carcinoma.

Clin Genitourin Cancer 2020 08 8;18(4):322-331.e2. Epub 2020 Jan 8.

Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, British Columbia, Canada; Department of Medical Oncology, BC Cancer, British Columbia, Canada.

Background: There is a lack of molecularly-informed biomarkers for patients with metastatic renal cell carcinoma (RCC). Plasma cell-free DNA (cfDNA) sequencing is a minimally-invasive alternative to tissue for profiling the genome in other cancers but relevance in metastatic RCC remains unclear.

Materials And Methods: Whole blood was collected from 55 patients with metastatic RCC. Plasma cfDNA and leukocyte DNA were subjected to targeted sequencing across 981 cancer genes. Matched tumor tissue from 14 patients was analyzed.

Results: Thirty-three percent of patients had evidence for RCC-derived circulating tumor DNA (ctDNA), significantly lower than patients with metastatic prostate or bladder cancer analyzed using the same approach. Among ctDNA-positive patients, ctDNA fraction averaged only 3.9% and showed no strong association with clinical variables. In these patients, the most commonly mutated genes were VHL, BAP1, and PBRM1, and matched tissue concordance was 77%. Evidence of somatic expansions unrelated to RCC, such as clonal hematopoiesis of indeterminate potential, were detected in 43% of patients. Pathogenic germline mutations in DNA repair genes were detected in 11% of patients. CtDNA-positive patients had shorter overall survival and progression-free survival on first-line therapy. Patients with evidence of clonal hematopoiesis of indeterminate potential had an intermediate prognosis compared with ctDNA-positive and -negative patients.

Conclusions: CfDNA sequencing enables straightforward characterization of the somatic RCC genome in a minority of patients with metastatic RCC. Owing to low ctDNA abundance, and the presence of non-RCC derived somatic clones in circulation, cfDNA sequencing may not be a simple pan-patient alternative to tissue biopsy in metastatic RCC.
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http://dx.doi.org/10.1016/j.clgc.2019.12.018DOI Listing
August 2020

Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma.

J Exp Clin Cancer Res 2020 Feb 10;39(1):33. Epub 2020 Feb 10.

Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Level 6, 2775-Laurel St, Vancouver, BC, V5Z 1M9, Canada.

Background: Renal cell carcinoma (RCC) is a highly vascular tumor and patients with low risk metastatic RCC of clear-cell histological sub-type (mccRCC) are treated with tyrosine-kinase inhibitors (TKIs), sunitinib, as the first-line of treatment. Unfortunately, TKI resistance eventually develops, and the underlying molecular mechanism is not well understood.

Methods: RCC cell-line with metastatic clear-cell histology (Caki-1), and patient samples were analysed to identify the role of Y-box binding protein 1 (YB-1) and ATP-binding cassette sub-family B member 1 (ABCB-1) in acquired sunitinib-resistance development. Caki-1 was conditioned with increasing sunitinib doses to recapitulate acquired resistance development in clinics. Sunitinib-conditioned and wild-type Caki-1 were subjected to cell viability assay, scratch assay, chicken embryo chorioallantoic membrane engraftment and proteomics analysis. Classical biochemical assays like flow cytometry, immunofluorescent staining, immunohistochemical staining, optical coherence tomography imaging, Western Blot and RT-PCR assays were applied to determine the possible mechanism of sunitinib-resistance development and the effect of drug treatments. Publicly available data was also used to determine the role of YB-1 upregulation in ccRCC and the patients' overall survival.

Results: We demonstrate that YB-1 and ABCB-1 are upregulated in sunitinib-resistant in vitro, ex vivo, in vivo and patient samples compared to the sensitive samples. This provides evidence to a mechanism of acquired sunitinib-resistance development in mccRCC. Furthermore, our results establish that inhibiting ABCB-1 with elacridar, in addition to sunitinib, has a positive impact on reverting sunitinib-resistance development in in vitro, ex vivo and in vivo models.

Conclusion: This work proposes a targeted therapy (elacridar and sunitinib) to re-sensitize sunitinib-resistant mccRCC and, possibly, slow disease progression.
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http://dx.doi.org/10.1186/s13046-020-1527-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011538PMC
February 2020

Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma.

Sci Rep 2020 02 6;10(1):2026. Epub 2020 Feb 6.

Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Clear-cell renal cell carcinoma (ccRCC) is a common therapy resistant disease with aberrant angiogenic and immunosuppressive features. Patients with metastatic disease are treated with targeted therapies based on clinical features: low-risk patients are usually treated with anti-angiogenic drugs and intermediate/high-risk patients with immune therapy. However, there are no biomarkers available to guide treatment choice for these patients. A recently published phase II clinical trial observed a correlation between ccRCC patients' clustering and their response to targeted therapy. However, the clustering of these groups was not distinct. Here, we analyzed the gene expression profile of 469 ccRCC patients, using featured selection technique, and have developed a refined 66-gene signature for improved sub-classification of patients. Moreover, we have identified a novel comprehensive expression profile to distinguish between migratory stromal and immune cells. Furthermore, the proposed 66-gene signature was validated using a different cohort of 64 ccRCC patients. These findings are foundational for the development of reliable biomarkers that may guide treatment decision-making and improve therapy response in ccRCC patients.
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http://dx.doi.org/10.1038/s41598-020-58804-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005147PMC
February 2020

Controversial issues in the management of patients with advanced prostate cancer: Results from a Canadian consensus forum.

Can Urol Assoc J 2020 Apr 5;14(4):E137-E149. Epub 2019 Nov 5.

BC Cancer Agency, University of British Columbia, Vancouver, BC, Canada.

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa.

Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians).

Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC.

Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.
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http://dx.doi.org/10.5489/cuaj.6082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124178PMC
April 2020
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