Publications by authors named "Frédéric Pouliot"

102 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

Interpreting Testosterone and Concomitant Prostate Specific Antigen Values during Androgen Deprivation Therapy for Recurrent Prostate Cancer.

J Urol 2021 Jun 29:101097JU0000000000001946. Epub 2021 Jun 29.

Department of Surgery, Faculty of Medicine, Université Laval; Centre de recherche CHU de Québec-Université Laval, Oncology Division; Quebec City, Quebec, Canada.

Purpose: Measurement of testosterone levels during androgen deprivation therapy (ADT) is broadly recommended, but how therapy should be altered in response to testosterone values during ADT remains controversial Our objective was therefore to evaluate the relation between testosterone and concomitant prostate specific antigen (PSA) levels during ADT on clinical outcomes.

Material And Methods: Patients from the continuous androgen deprivation (CAD) arm of the PR.7 trial of intermittent ADT for biochemically recurrent prostate cancer following radiotherapy were included. Statistical analyses evaluated the prognostic importance of testosterone levels during ADT relative to concomitant PSA levels. We similarly evaluated whether the number of testosterone breakthroughs >1.7nmol/L predicted the time to castrate-resistant prostate cancer (CRPC), cancer specific survival (CSS) or overall survival (OS) with Kaplan-Meier and Cox-regression analyses.

Results: Overall, the prognostic importance of testosterone on outcomes was eclipsed by the prognostic value of concomitant PSA values. The occurrence of testosterone values >0.7nmol/L in the first year of therapy was associated with subsequent rises >1.7nmol/L but the number of testosterone breakthroughs per patient had no relationship to the risk of CRPC, CSS or OS. A time-dependent adjusted analysis indicated as expected that PSA values were prognostic, but there was no association of relative cumulative testosterone exposure with outcomes.

Conclusions: In this large-scale trial with long follow up, breakthrough testosterone was unrelated to time to CRPC, CSS, or OS. Castrate testosterone values during ADT for recurrent prostate cancer provides prognostic information which must be considered alongside the time since ADT initiation and concomitant PSA values.
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http://dx.doi.org/10.1097/JU.0000000000001946DOI Listing
June 2021

Active Surveillance in Metastatic Renal Cell Carcinoma: Results From the Canadian Kidney Cancer Information System.

Clin Genitourin Cancer 2021 May 15. Epub 2021 May 15.

Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada.

Background: Active surveillance (AS) is a commonly used strategy in patients with slow-growing disease. We aimed to assess the outcomes and safety of AS in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: We used the Canadian Kidney Cancer information system (CKCis) to identify patients with mRCC diagnosed between January 1, 2011, and December 31, 2016. The AS strategy was defined as (1) the start of systemic therapy ≥ 6 months after diagnosis of mRCC, or (2) never receiving systemic therapy for mRCC with an overall survival (OS) of ≥1 year. Patients starting systemic treatment <6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until first-line treatment failure (TTF) were compared between the two cohorts.

Results: A total of 853 patients met the criteria for AS (cohort A). Of these, 364 started treatment >6 months after their initial diagnosis (cohort A1) and 489 never started systemic therapy (cohort A2); 827 patients received immediate systemic treatment (cohort B). The 5-year OS probability was significantly greater for cohort A than for cohort B (70% vs. 33.6%; P < .0001). After adjusting for International Metastatic RCC Database Consortium risk criteria and age, both OS (hazard ratio [HR] = 0.58; 95% confidence interval [CI], 0.47-0.70; P < .0001) and TTF (HR = 0.72; 95% CI, 0.60-0.85; P = .0002) were greater in cohort A1 compared with B. For cohort A1, the median time on AS was 14.2 months (range, 6-71).

Conclusions: Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of patients may be safely observed without immediate initiation of systemic therapy.
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http://dx.doi.org/10.1016/j.clgc.2021.05.004DOI Listing
May 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

F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is accurate for high-grade prostate cancer bone staging when compared to bone scintigraphy.

Can Urol Assoc J 2021 Mar 18. Epub 2021 Mar 18.

Oncology Division, CHU de Québec Research Center, Quebec, QC, Canada.

Introduction: In this study, we compared F-FDG-postron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if F-FDG-PET/CT could be used alone as a staging modality.

Methods: Men with localized high-grade PCa (n=256, Gleason 8-10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and F-FDGPET/CT. We compared on a per-patient basis the accuracy of the two imaging modalities, taking intermodality agreement as the standard of truth (SOT).

Results: F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2-4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions.

Conclusions: F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDG-uptake is also a biomarker of failure to radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa.
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http://dx.doi.org/10.5489/cuaj.7107DOI Listing
March 2021

Proximity-dependent Mapping of the Androgen Receptor Identifies Kruppel-like Factor 4 as a Functional Partner.

Mol Cell Proteomics 2021 Feb 26;20:100064. Epub 2021 Feb 26.

Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Axe Oncologie, Québec, Quebec, Canada; Centre de recherche sur le cancer de l'Université Laval, Québec, Quebec, Canada; PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, Quebec, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Faculté de Médecine, Université Laval, Québec, Quebec, Canada. Electronic address:

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the third cause of cancer mortality. PCa initiation and growth are driven by the androgen receptor (AR). The AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. Here, we report an AR signaling network generated using BioID proximity labeling proteomics in androgen-dependent LAPC4 cells. We identified 31 AR-associated proteins in nonstimulated cells. Strikingly, the AR signaling network increased to 182 and 200 proteins, upon 24 h or 72 h of androgenic stimulation, respectively, for a total of 267 nonredundant AR-associated candidates. Among the latter group, we identified 213 proteins that were not previously reported in databases. Many of these new AR-associated proteins are involved in DNA metabolism, RNA processing, and RNA polymerase II transcription. Moreover, we identified 44 transcription factors, including the Kru¨ppel-like factor 4 (KLF4), which were found interacting in androgen-stimulated cells. Interestingly, KLF4 repressed the well-characterized AR-dependent transcription of the KLK3 (PSA) gene; AR and KLF4 also colocalized genome-wide. Taken together, our data report an expanded high-confidence proximity network for AR, which will be instrumental to further dissect the molecular mechanisms underlying androgen signaling in PCa cells.
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http://dx.doi.org/10.1016/j.mcpro.2021.100064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050775PMC
February 2021

A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with F-DCFPyL in Prostate Cancer Patients (OSPREY).

J Urol 2021 07 26;206(1):52-61. Epub 2021 Feb 26.

Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer.

Materials And Methods: Two patient populations underwent F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated.

Results: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively.

Conclusions: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.
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http://dx.doi.org/10.1097/JU.0000000000001698DOI Listing
July 2021

Diagnostic Performance of F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study.

Clin Cancer Res 2021 Jul 23;27(13):3674-3682. Epub 2021 Feb 23.

University of California San Francisco, San Francisco, California.

Purpose: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging.

Experimental Design: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety.

Results: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8-80.4). A total of 63.9% of evaluable patients had a change in intended management after F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by F-DCFPyL-PET/CT by central readers).

Conclusions: Performance of F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4573DOI Listing
July 2021

Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.

J Clin Oncol 2021 Mar 2;39(9):1029-1039. Epub 2021 Feb 2.

Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.

Purpose: Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non-clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC.

Methods: Patients with histologically confirmed, measurable (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) nccRCC and no prior systemic therapy received pembrolizumab 200 mg intravenously once every 3 weeks for ≤ 24 months. The primary end point was objective response rate (ORR) per RECIST v1.1.

Results: Among enrolled patients (N = 165), 71.5% had confirmed papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Most patients (67.9%) had intermediate or poor International Metastatic RCC Database Consortium risk status and tumors with programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8). In all patients, the ORR was 26.7%. The median duration of response was 29.0 months; 59.7% of responses lasted ≥ 12 months. The ORR by CPS ≥ 1 and CPS < 1 status was 35.3% and 12.1%, respectively. The ORR by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified. Overall, the median progression-free survival was 4.2 months (95% CI, 2.9 to 5.6); the 24-month rate was 18.6%. The median overall survival was 28.9 months (95% CI, 24.3 months to not reached); the 24-month rate was 58.4%. Overall, 69.7% of patients reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%). Two deaths were treatment related (pneumonitis and cardiac arrest).

Conclusion: First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.
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http://dx.doi.org/10.1200/JCO.20.02365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078262PMC
March 2021

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

J Urol 2021 May 21;205(5):1303-1309. Epub 2020 Dec 21.

Division of Urology, Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

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 Tc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m 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 m). 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 m in the hypothermia group and -7.8 ml/minute/1.73 m in the control group (mean difference 1.2 ml/minute/1.73 m, 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 m; mean difference 0.5 ml/minute/1.73 m, 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.
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http://dx.doi.org/10.1097/JU.0000000000001517DOI Listing
May 2021

Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial.

Lancet Oncol 2020 12 23;21(12):1563-1573. Epub 2020 Oct 23.

Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

Background: The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma.

Methods: In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (≥18 years old) with treatment-naive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intention-to-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331.

Findings: Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30·6 months (IQR 27·2-34·2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35·7 months [95% CI 33·3-not reached] with sunitinib); hazard ratio [HR] 0·68 [95% CI 0·55-0·85], p=0·0003) and progression-free survival (median 15·4 months [12·7-18·9] vs 11·1 months [9·1-12·5]; 0·71 [0·60-0·84], p<0·0001). The most frequent (≥10% patients in either group) treatment-related grade 3 or worse adverse events were hypertension (95 [22%] of 429 patients in the pembrolizumab plus axitinib group vs 84 [20%] of 425 patients in the sunitinib group), alanine aminotransferase increase (54 [13%] vs 11 [3%]), and diarrhoea (46 [11%] vs 23 [5%]). No new treatment-related deaths were reported since the first interim analysis.

Interpretation: With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunitinib. These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma.

Funding: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
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http://dx.doi.org/10.1016/S1470-2045(20)30436-8DOI Listing
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

A prospective, multisite study analyzing the percentage of urological cases that can be completely managed by telemedicine.

Can Urol Assoc J 2020 Oct;14(10):319-321

Division of Urology, Department of Surgery, CHU de Québec-Université Laval, Quebec City, QC, Canada.

Introduction: The COVID-19 pandemic has accelerated the development of telemedicine due to confinement measures. However, the percentage of outpatient urological cases that could be managed completely by telemedicine outside of the COVID-19 pandemic remains to be determined. We conducted a prospective, multisite study involving all urologists working in the region of Quebec City.

Methods: During the first four weeks of the regional confinement, 18 pediatric and adult urologists were asked to determine, after each telemedicine appointment, if it translated into a complete (CCM), incomplete (ICM), or suboptimal case management (SCM, adequate only in the context of the pandemic).

Results: A total of 1679 appointments representing all urological areas were registered. Overall, 67.6% (95% confidence interval [CI] 65.3; 69.8), 27.1% (25.0; 29.3), and 4.3% (3.5; 5.4) were reported as CCM, SCM, and ICM, respectively. The CCM ratio varied according to the reason for consultation, with cancer suspicion (52.9% [42.9; 62.8]) and pediatric reasons (38.0% [30.0; 46.6]) showing the lowest CCM percentages. CCM percentages also varied significantly based on the setting where it was performed, ranging from 61.1% (private clinic) to 86.8% (endourology and general hospital).

Conclusions: We show that two-thirds of all urological outpatient cases could be completely managed by telemedicine outside of the pandemic. After the pandemic, it will be important to incorporate telemedicine as an alternative for a patient's first or followup visit, especially those with geographical, pathological, and socioeconomic considerations.
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http://dx.doi.org/10.5489/cuaj.6862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716828PMC
October 2020

TGFβ Signaling in the Tumor Microenvironment.

Adv Exp Med Biol 2021 ;1270:89-105

Oncology Division, CHU de Québec Research Center, Quebec, QC, Canada.

Transforming growth factor beta (TGFβ) is a pleiotropic growth factor. Under normal physiological conditions, TGFβ maintains homeostasis in mammalian tissues by restraining the growth of cells and stimulating apoptosis. However, the role of TGFβ signaling in the carcinogenesis is complex. TGFβ acts as a tumor suppressor in the early stages of disease and as a tumor promoter in its later stages where cancer cells have been relieved from TGFβ growth controls. Overproduction of TGFβ by cancer cells lead to a local fibrotic and immune-suppressive microenvironment that fosters tumor growth and correlates with invasive and metastatic behavior of the cancer cells. Here, we present an overview of the complex biology of the TGFβ family, and we discuss the roles of TGFβ signaling in carcinogenesis and how this knowledge is being leveraged to develop TGFβ inhibition therapies against the tumor.
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http://dx.doi.org/10.1007/978-3-030-47189-7_6DOI 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

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

Achieving the "trifecta" with open versus minimally invasive partial nephrectomy.

World J Urol 2021 May 12;39(5):1569-1575. Epub 2020 Jul 12.

University of British Columbia, Level 6, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.

Introduction: The "trifecta" is a summary measure of outcome after partial nephrectomy (PN) that encompasses three parameters: negative surgical margin, ≤ 10% decrease in post-operative estimated glomerular filtration rate (eGFR) and absence of urological complications. We assessed trifecta rates in patients undergoing open (OPN), laparoscopic (LPN), and robotic PN (RPN) for a clinical T1 renal mass (≤ 7 cm).

Methods: Clinical and pathologic parameters were extracted from the prospectively maintained Canadian Kidney Cancer Information System for patients treated between January 2011 and October 2018. Comparisons between groups were made using Kruskal-Wallis test for continuous variables and Chi-squared independence test for categorical variables. Multivariable analysis was performed to identify predictors of each component of the trifecta and the trifecta itself.

Results: Of 1708 total patients, 746 underwent OPN, 678 LPN, and 284 RPN for a T1 renal mass. A 'trifecta' was achieved in 53% OPN, 52% LPN and 47% RPN (p = 0.194). On multivariable analysis, OPN and LPN were associated with less frequent post-operative decline in eGFR and more frequent trifecta when compared to RPN, but there was no difference between OPN and LPN. OPN also predicted a higher rate of negative margins compared to RPN but not LPN.

Conclusion: After correction for confounding variables, OPN and LPN were more likely than RPN to achieve the trifecta, which appeared to be due primarily to loss of renal function. No difference was observed between OPN and LPN. Analyses were limited by the lack of nephrometry score.
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http://dx.doi.org/10.1007/s00345-020-03349-yDOI Listing
May 2021

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

Testosterone Breakthrough Rates during Androgen Deprivation Therapy for Castration Sensitive Prostate Cancer.

J Urol 2020 Sep 25;204(3):416-426. Epub 2020 Feb 25.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: Androgen deprivation therapy is an established therapy for castration sensitive prostate cancer and recent studies have observed that patients whose testosterone levels are suppressed below 0.7 nmol/l have improved outcomes. Testosterone breakthrough, or a rise in testosterone above a target threshold after the first month of androgen deprivation therapy, is generally associated with treatment deficiency. The purpose of this review is to summarize breakthrough rate data and explore the relationship to clinical outcomes in patients with castration sensitive prostate cancer receiving androgen deprivation therapy.

Materials And Methods: Our systematic search identified 45 studies with a total of 52 cohorts representing 6,047 total patients reporting testosterone breakthrough rates or derivative measures above the thresholds of 1.7 nmol/l (51 cohorts, 6,015 patients) or 0.7 nmol/l (15 cohorts, 2,495 patients).

Results: Significantly higher weighted mean breakthrough rates were seen for the 0.7 nmol/l threshold compared to 1.7 nmol/l (41.3% vs 6.9%, p <0.0001). A significant association between breakthrough rates and worse clinical outcomes overall was not found, although when larger trials (sample size greater than 100) and higher event rates (greater than 50%) were considered for the lowest threshold, significant associations between breakthrough rates and clinical outcomes were observed. Clinical factors such as administration and monitoring frequency, type of testosterone assay and type of androgen deprivation therapy did not significantly affect breakthrough rates, although nonvalidated assays were associated with a large degree of variability.

Conclusions: Results from our analysis indicate that testosterone breakthroughs likely result in worse clinical outcomes and should be avoided. Moreover, there is a need to standardize assessment of testosterone levels both clinically and in the research context to better inform treatment decisions and improve the reliability and comparability of results across studies.
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http://dx.doi.org/10.1097/JU.0000000000000809DOI Listing
September 2020
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