Publications by authors named "Antonio Finelli"

342 Publications

Role of multiparametric MRI in long-term surveillance following focal laser ablation of prostate cancer.

Br J Radiol 2021 Jul 29:20210414. Epub 2021 Jul 29.

Joint Department of Medical Imaging, University of Toronto, University Health Network - Mount Sinai Hospital - Women's College Hospital, Toronto, ON, Canada.

Objective: Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease.

Methods: Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for -weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results.

Results: 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point.

Conclusion: mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study.

Advances In Knowledge: Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.
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http://dx.doi.org/10.1259/bjr.20210414DOI Listing
July 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

Comparison of Joint and Landmark Modeling for Predicting Cancer Progression in Men With Castration-Resistant Prostate Cancer: A Secondary Post Hoc Analysis of the PREVAIL Randomized Clinical Trial.

JAMA Netw Open 2021 Jun 1;4(6):e2112426. Epub 2021 Jun 1.

Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

Importance: Dynamic prediction models may help predict radiographic disease progression in advanced prostate cancer.

Objective: To assess whether dynamic prediction models aid prognosis of radiographic progression risk, using ongoing longitudinal prostate-specific antigen (PSA) assessments.

Design, Setting, And Participants: This prognostic study used data from the PREVAIL study to compare dynamic models for predicting disease progression. The PREVAIL study was a phase 3, multinational, double-blind, placebo-controlled randomized clinical trial of enzalutamide for prostate cancer conducted from September 2010 to September 2012. A total of 773 men with metastatic castration-resistant prostate cancer (CRPC) who had never received chemotherapy and had no baseline visceral disease were treated with enzalutamide. For illustration, 4 patients were selected based on PSA kinetics or PSA response in case studies. Data were analyzed from July 2018 to September 2019.

Main Outcomes And Measures: Landmark and joint models were applied to dynamically predict radiographic progression-free survival (PFS) using longitudinal PSA profile, baseline PSA, lactate dehydrogenase, and hemoglobin levels. The main outcome was radiographic PFS as predicted using landmark and joint models. Current PSA and PSA change were considered longitudinal biomarkers possibly associated with radiographic PFS. Predictive performance was evaluated using Brier score for overall prediction errors (PEs) and area under the curve (AUC) for model discriminative capability. Case studies were illustrated using dynamic prediction plots.

Results: A total of 763 men with metastatic CRPC treated with enzalutamide (mean [SD] age, 71.2 [8.5] years; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 28.4 [4.6]) were included in the analysis. Current PSA and PSA change were associated with radiographic PFS in all models. Adding the PSA slope, compared with the landmark models using current PSA alone, improved the prediction of 5-month prospect of radiographic progression, with relative gains of 5.7% in prediction (PE [SE], 0.132 [0.008] vs 0.140 [0.008]) and 7.7% in discrimination (AUC [SE], 0.800 [0.018] vs 0.743 [0.018]) at month 10. In joint models with linear vs nonlinear PSA, prediction of 5-month risk of radiographic progression was improved when PSA trajectories were not assumed to be linear, with 8.0% relative gain in prediction (PE [SE], 0.150 [0.006] vs 0.138 [0.005]) and 19.4% relative gain in discrimination (AUC [SE], 0.653 [0.022] vs 0.780 [0.016]) at month 10. Predictions were affected by amount of marker information accumulated and prespecified assumptions. PSA changes affected progression risk more strongly at later vs earlier follow-up.

Conclusions And Relevance: This prognostic study found that prediction of radiographic PFS was improved when longitudinal PSA information was added to baseline variables. In a population of patients with metastatic CRPC, dynamic predictions using landmark or joint models may help identify patients at risk of progression.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.12426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207237PMC
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

Establishing a global quality of care benchmark report.

Health Informatics J 2021 Apr-Jun;27(2):14604582211015704

Cancer Council Victoria, Australia.

Background: The Movember funded TrueNTH Global Registry (TNGR) aims to improve care by collecting and analysing a consistent dataset to identify variation in disease management, benchmark care delivery in accordance with best practice guidelines and provide this information to those in a position to enact change. We discuss considerations of designing and implementing a quality of care report for TNGR.

Methods: Eleven working group sessions were held prior to and as reports were being built with representation from clinicians, data managers and investigators contributing to TNGR. The aim of the meetings was to understand current data display approaches, share literature review findings and ideas for innovative approaches. Preferred displays were evaluated with two surveys (survey 1: 5 clinicians and 5 non-clinicians, 83% response rate; survey 2: 17 clinicians and 18 non-clinicians, 93% response rate).

Results: Consensus on dashboard design and three data-display preferences were achieved. The dashboard comprised two performance summary charts; one summarising site's relative quality indicator (QI) performance and another to summarise data quality. Binary outcome QIs were presented as funnel plots. Patient-reported outcome measures of function score and the extent to which men were bothered by their symptoms were presented in bubble plots. Time series graphs were seen as providing important information to supplement funnel and bubble plots. R Markdown was selected as the software program principally because of its excellent analytic and graph display capacity, open source licensing model and the large global community sharing program code enhancements.

Conclusions: International collaboration in creating and maintaining clinical quality registries has allowed benchmarking of process and outcome measures on a large scale. A registry report system was developed with stakeholder engagement to produce dynamic reports that provide user-specific feedback to 132 participating sites across 13 countries.
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http://dx.doi.org/10.1177/14604582211015704DOI Listing
June 2021

Avoiding Unnecessary Biopsy: MRI-based Risk Models versus a PI-RADS and PSA Density Strategy for Clinically Significant Prostate Cancer.

Radiology 2021 Aug 25;300(2):369-379. Epub 2021 May 25.

From the Department of Diagnostic and Interventional Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany (D.D.); Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 600 University Ave, Toronto, ON, Canada M5G 1X5 (D.D., G.M.H., X.D., E.S.M., A.Z., M.A.H.); Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada (D.D., G.M.H., S.G., E.S.M., A.T., M.A.H.); Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada (N.F., R.H., G.K., A.Z., A.F., N.P.); Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada (T.v.d.K.); and Department of Surgery, Division of Urology, Mount Sinai Hospital, Toronto, ON, Canada (A.Z.).

Background In validation studies, risk models for clinically significant prostate cancer (csPCa; Gleason score ≥3+4) combining multiparametric MRI and clinical factors have demonstrated poor calibration (over- and underprediction) and limited use in avoiding unnecessary prostate biopsies. Purpose MRI-based risk models following local recalibration were compared with a strategy that combined Prostate Imaging Data and Reporting System (PI-RADS; version 2) and prostate-specific antigen density (PSAd) to assess the potential reduction of unnecessary prostate biopsies. Materials and Methods This retrospective study included 385 patients without prostate cancer diagnosis who underwent multipara-metric MRI (PI-RADS category ≥3) and MRI-targeted biopsy between 2015 and 2019. Recalibration and selection of the best-performing MRI model (MRI-European Randomized Study of Screening for Prostate Cancer [ERSPC], van Leeuwen, Radtke, and Mehralivand models) were undertaken in cohort C1 ( = 242; 2015-2017). The impact on biopsy decisions was compared with an alternative strategy (no biopsy for PI-RADS category 3 plus PSAd < 0.1 ng/mL per milliliter) in cohort C2 ( = 143; 2018-2019). Discrimination, calibration, and clinical utility were assessed by using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. Results The prevalence of csPCa was 38% (93 of 242 patients) and 45% (64 of 143 patients) in cohorts C1 and C2, respectively. Decision curve analysis demonstrated the highest net benefit for the van Leeuwen and Mehralivand models in C1. Used for biopsy decisions in C2, van Leeuwen (AUC, 0.84; 95% CI: 0.77, 0.9) and Mehralivand (AUC, 0.79; 95% CI: 0.72, 0.86) enabled no net benefit at a risk threshold of 10%. Up to a risk threshold of 15%, net benefit remained inferior to the PI-RADS plus PSAd strategy, which avoided biopsy in 63 per 1000 men, without missing csPCa. Without prior recalibration in C1, three of four models (MRIERSPC, Radtke, Mehralivand) were poorly calibrated and not clinically useful in C2. Conclusion The number of unnecessary prostate biopsies in men with positive MRI may be safely reduced by using a prostate-specific antigen density-based strategy. In a risk-averse scenario, this strategy enabled better biopsy decisions compared with MRI-based risk models. ©RSNA, 2021 .
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http://dx.doi.org/10.1148/radiol.2021204112DOI Listing
August 2021

Virtual care for prostate cancer survivorship: protocol for an evaluation of a nurse-led algorithm-enhanced virtual clinic implemented at five cancer centres across Canada.

BMJ Open 2021 04 21;11(4):e045806. Epub 2021 Apr 21.

Centre for Global eHealth Innovation, University Health Network, Toronto, Ontario, Canada.

Introduction: Prostate cancer (PCa) is the most common cancer in Canadian men. Current models of survivorship care are no longer adequate to address the chronic and complex survivorship needs of patients today. Virtual care models for cancer survivorship have recently been associated with comparable clinical outcomes and lower costs to traditional follow-up care, with patients favouring off-site and on-demand visits. Building on their viability, our research group conceived the Ned Clinic-a virtual PCa survivorship model that provides patients with access to lab results, collects patient-reported outcomes, alerts clinicians to emerging issues, and promotes patient self-care. Despite the promise of the Ned Clinic, the model remains limited by its dependence on oncology specialists, lack of an autonomous triage algorithm, and has only been implemented among PCa survivors living in Ontario.

Methods And Analysis: Our programme of research comprises two main research objectives: (1) to evaluate the process and cost of implementing and sustaining five nurse-led virtual PCa survivorship clinics in three provinces across Canada and identify barriers and facilitators to implementation success and (2) to assess the impact of these virtual clinics on implementation and effectiveness outcomes of enrolled PCa survivors. The design phase will involve developing an autonomous triage algorithm and redesigning the Ned Clinic towards a nurse-led service model. Site-specific implementation plans will be developed to deploy a localised nurse-led virtual clinic at each centre. Effectiveness will be evaluated using a historical control study comparing the survivorship outcomes of 300 PCa survivors enrolled in the Ned Clinic with 300 PCa survivors receiving traditional follow-up care.

Ethics And Dissemination: Appropriate site-specific ethics approval will be secured prior to each research phase. Knowledge translation efforts will include diffusion, dissemination, and application approaches to ensure that knowledge is translated to both academic and lay audiences.
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http://dx.doi.org/10.1136/bmjopen-2020-045806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061848PMC
April 2021

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

Urol Oncol 2021 06 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

A systematic review and meta-analysis of unplanned hospital visits and re-admissions following radical prostatectomy for prostate cancer.

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

Weill-Cornell School of Medicine, Cornell University, New York, NY, United States.

Introduction: Unplanned visits (UPV) - re-admissions and emergency room (ER) visits - are markers of healthcare system quality. Radical prostatectomy (RP) is a commonly performed cancer procedure, where variation in UPV represents a gap in care for prostate cancer patients. Here, we systematically synthesize the rates, reasons, predictors, and interventions for UPV after RP, to inform evidence-based quality improvement (QI) initiatives.

Methods: A systematic review was performed for studies from 2000-2020 using keywords: "readmission," "emergency room/department," "unplanned visit," and "prostatectomy." Studies that focused on UPV following RP and that reported rates, reasons, predictors, or interventions, were included. Data was extracted via a standardized form. Meta-analysis was completed.

Results: Sixty studies, with 406 107 RP patients, were eligible; 16 028 UPV events (~5%) were analyzed from 317 050 RP patients. UPV rates after RP varied between studies (ER visit range 6-24%; re-admissions range 0-56%). The 30-day and 90-day ER visit rates were 12% and 14%, respectively; the 30-day and 90-day re-admission rates were 4% and 9%, respectively. A total of 55% of all re-admissions after RP are directly due to postoperative genitourinary (GU)-related complications such as strictures, obstructions, fistula, bladder-related, incontinence, urine leak, renal problems, and other unspecified urinary complications. The next most common readmission reasons were anastomosis-related, infection-related, cardiovascular/pulmonary events, and wound-related issues. Thirty-four percent of all ER visits after RP are directly due to urine-related issues such as retention, urinoma, obstruction, leak, and catheter problems. The next most common ER visit reasons were abdominal/gastrointestinal issues, infection-related, venous thromboembolic events, and wound-related issues. Predictors for increased re-admission included: open RP, lymph node dissection, Charlson comorbidity index≥2, low surgeon/hospital case volume, and socioeconomic determinants of health. Of the 10 interventions evaluated, a 3.4% average reduction in UPV rate was observed, highlighting an approximate two-fold decrease. Meta-analysis demonstrated a significant benefit of interventions over controls with odds ratio 0.62 (95% confidence interval 0.46-0.84). Interventions that used multidisciplinary, nurse-centered, programs, with patient self-care/empowerment were more beneficial than algorithmic patient care pathways and preoperative patient education.

Conclusions: Twenty years of international, retrospective, experience suggests UPV after RP are often related to GU complications, infection- or wound-related factors. QI interventions to reduce UPV should target these factors. While many re-admissions after RP appear to be unavoidable, ER visits have more opportunity for volume reduction by QI. The interventions evaluated herein have potential to reduce UPV after RP.
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http://dx.doi.org/10.5489/cuaj.6931DOI Listing
March 2021

Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis.

Eur Urol 2021 Mar 5. Epub 2021 Mar 5.

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada; TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. Electronic address:

Background: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches.

Objective: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT).

Design/setting/participants: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible.

Interventions: All patients underwent [F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT.

Outcome Measurements/statistical Analysis: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1.

Results: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed.

Conclusions: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa.

Patient Summary: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.
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http://dx.doi.org/10.1016/j.eururo.2021.02.031DOI Listing
March 2021

Benefit of a more extended pelvic lymph node dissection among patients undergoing radical prostatectomy for localized prostate cancer: A causal mediation analysis.

Prostate 2021 Apr 18;81(5):286-294. Epub 2021 Feb 18.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background: The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect).

Methods: Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect).

Results: Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75).

Conclusions: Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.
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http://dx.doi.org/10.1002/pros.24105DOI Listing
April 2021

A Population-based Study Comparing Outcomes for Patients With Metastatic Castrate Resistant Prostate Cancer Treated by Urologists or Medical Oncologists With First Line Abiraterone Acetate or Enzalutamide.

Urology 2021 Jul 13;153:147-155. Epub 2021 Feb 13.

Division of Urology, University Health Network, University of Toronto. Electronic address:

Objectives: To compare toxicity and all-cause mortality for mCRPC patients receiving first line oral systemic therapy prescribed by medical oncologists and urologists.

Methods: Population-based retrospective cohort study of chemotherapy-naïve men aged ≥66 years treated for mCRPC with first-line abiraterone or enzalutamide based on administrative health data (Ontario, Canada, 2012-2017). Primary outcomes were hospitalizations/ER visits for any cause or treatment-related toxicity during first-line mCRPC treatment. Secondary outcome was all-cause mortality. We calculated hazard ratios (HRs) comparing outcomes for different medical specialties using multivariable Cox proportional hazards models.

Results: Among 3405 mCRPC patients, 2407 (70.7%) received abiraterone and 998 (29.3%) received enzalutamide. 1786 (52.5%) patients visited the ER or were hospitalized. Men treated by medical oncologists had an increased risk of hospitalization/ER visits (HR1.16, 95%CI 1.03-1.31; P = .02), toxicity-related visits (HR1.34, 95%CI 1.08-1.69; P = .01), and mortality (HR1.16, 95%CI 1.02-1.33; P = .02) compared to urologists. Limited information was available, beyond PSA adjustment and prior treatment, on patient disease burden.

Conclusion: We observed fewer hospital visits overall and for treatment-related toxicity for mCRPC patients who were prescribed first line abiraterone or enzalutamide by urologists compared to medical oncologists. These differences may result from higher prostate cancer disease burden in patients managed by medical oncologists, and/or other unmeasured differences in patient management between specialties.
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http://dx.doi.org/10.1016/j.urology.2020.11.080DOI Listing
July 2021

Natural history of untreated kidney cancer.

World J Urol 2021 Feb 16. Epub 2021 Feb 16.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1007/s00345-020-03578-1DOI Listing
February 2021

Comparison of Multiparametric Magnetic Resonance Imaging-Targeted Biopsy With Systematic Transrectal Ultrasonography Biopsy for Biopsy-Naive Men at Risk for Prostate Cancer: A Phase 3 Randomized Clinical Trial.

JAMA Oncol 2021 04;7(4):534-542

Toronto General Hospital, Department of Radiology, University of Toronto, Toronto, Ontario, Canada.

Importance: Magnetic resonance imaging (MRI) with targeted biopsy is an appealing alternative to systematic 12-core transrectal ultrasonography (TRUS) biopsy for prostate cancer diagnosis, but has yet to be widely adopted.

Objective: To determine whether MRI with only targeted biopsy was noninferior to systematic TRUS biopsies in the detection of International Society of Urological Pathology grade group (GG) 2 or greater prostate cancer.

Design, Setting, And Participants: This multicenter, prospective randomized clinical trial was conducted in 5 Canadian academic health sciences centers between January 2017 and November 2019, and data were analyzed between January and March 2020. Participants included biopsy-naive men with a clinical suspicion of prostate cancer who were advised to undergo a prostate biopsy. Clinical suspicion was defined as a 5% or greater chance of GG2 or greater prostate cancer using the Prostate Cancer Prevention Trial Risk Calculator, version 2. Additional criteria were serum prostate-specific antigen levels of 20 ng/mL or less (to convert to micrograms per liter, multiply by 1) and no contraindication to MRI.

Interventions: Magnetic resonance imaging-targeted biopsy (MRI-TB) only if a lesion with a Prostate Imaging Reporting and Data System (PI-RADS), v 2.0, score of 3 or greater was identified vs 12-core systematic TRUS biopsy.

Main Outcome And Measures: The proportion of men with a diagnosis of GG2 or greater cancer. Secondary outcomes included the proportion who received a diagnosis of GG1 prostate cancer; GG3 or greater cancer; no significant cancer but subsequent positive MRI results and/or GG2 or greater cancer detected on a repeated biopsy by 2 years; and adverse events.

Results: The intention-to-treat population comprised 453 patients (367 [81.0%] White, 19 [4.2%] African Canadian, 32 [7.1%] Asian, and 10 [2.2%] Hispanic) who were randomized to undergo TRUS biopsy (226 [49.9%]) or MRI-TB (227 [51.1%]), of which 421 (93.0%) were evaluable per protocol. A lesion with a PI-RADS score of 3 or greater was detected in 138 of 221 men (62.4%) who underwent MRI, with 26 (12.1%), 82 (38.1%), and 30 (14.0%) having maximum PI-RADS scores of 3, 4, and 5, respectively. Eighty-three of 221 men who underwent MRI-TB (37%) had a negative MRI result and avoided biopsy. Cancers GG2 and greater were identified in 67 of 225 men (30%) who underwent TRUS biopsy vs 79 of 227 (35%) allocated to MRI-TB (absolute difference, 5%, 97.5% 1-sided CI, -3.4% to ∞; noninferiority margin, -5%). Adverse events were less common in the MRI-TB arm. Grade group 1 cancer detection was reduced by more than half in the MRI arm (from 22% to 10%; risk difference, -11.6%; 95% CI, -18.2% to -4.9%).

Conclusions And Relevance: Magnetic resonance imaging followed by selected targeted biopsy is noninferior to initial systematic biopsy in men at risk for prostate cancer in detecting GG2 or greater cancers.

Trial Registration: ClinicalTrials.gov Identifier: NCT02936258.
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http://dx.doi.org/10.1001/jamaoncol.2020.7589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863017PMC
April 2021

MRI-guided Focused Ultrasound Ablation for Localized Intermediate-Risk Prostate Cancer: Early Results of a Phase II Trial.

Radiology 2021 Mar 2;298(3):695-703. Epub 2021 Feb 2.

From the Joint Department of Medical Imaging (S.G., R.C., E.H., M.A.H., W.K.), Division of Urology, Department of Surgical Oncology (A.F., K.C., S.J., A.K., A.R.Z., R.J.H., N.P.), Biostatistics Department, Princess Margaret Cancer Centre (X.L.), Department of Anaesthesia (S.M.), and Department of Pathology, Laboratory Medicine Program (T.H.v.d.K.), University Health Network-Mount Sinai Hospital-Women's, College Hospital, University of Toronto, 585 University Ave, Toronto, ON, Canada M5G 2N2; and Department of Urology, Oakville Trafalgar Memorial Hospital, Toronto, Canada (P.F.I.).

Background To reduce adverse effects of whole-gland therapy, participants with localized clinically significant prostate cancer can undergo MRI-guided focal therapy. Purpose To explore safety and early oncologic and functional outcomes of targeted focal high-intensity focused ultrasound performed under MRI-guided focused ultrasound for intermediate-risk clinically significant prostate cancer. Materials and Methods In this prospective phase II trial, between February 2016 and July 2019, men with unifocal clinically significant prostate cancer visible at MRI were treated with transrectal MRI-guided focused ultrasound. The primary end point was the 5-month biopsy (last recorded in December 2019) with continuation to the 24-month follow-up projected to December 2021. Real-time ablation monitoring was performed with MR thermography. Nonperfused volume was measured at treatment completion. Periprocedural complications were recorded. Follow-up included International Prostate Symptom Score (IPSS) and International Index of Erectile Function-15 (IIEF-15) score at 6 weeks and 5 months, and multiparametric MRI and targeted biopsy of the treated area at 5 months. The generalized estimating equation model was used for statistical analysis, and the Holm method was used to adjust value. Results Treatment was successfully completed in all 44 men, 36 with grade group (GG) 2 and eight with GG 3 disease (median age, 67 years; interquartile range [IQR], 62-70 years). No major treatment-related adverse events occurred. Forty-one of 44 participants (93%; 95% CI: 82, 98) were free of clinically significant prostate cancer (≥6 mm GG 1 disease or any volume ≥GG 2 disease) at the treatment site at 5-month biopsy (median, seven cores). Median IIEF-15 and IPSS scores were similar at baseline and at 5 months (IIEF-15 score at baseline, 61 [IQR, 34-67] and at 5 months, 53 [IQR, 24-65.5], = .18; IPSS score at baseline, 3.5 [IQR, 1.8-7] and at 5 months, 6 [IQR, 2-7.3], = .43). Larger ablations (≥15 cm) compared with smaller ones were associated with a decline in IIEF-15 scores at 6 weeks (adjusted < .01) and at 5 months (adjusted = .07). Conclusion Targeted focal therapy of intermediate-risk prostate cancer performed with MRI-guided focused ultrasound ablation was safe and had encouraging early oncologic and functional outcomes. © RSNA, 2021 See also the editorial by Tempany-Afdhal in this issue.
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http://dx.doi.org/10.1148/radiol.2021202717DOI Listing
March 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

Novel Liquid Biomarkers and Innovative Imaging for Kidney Cancer Diagnosis: What Can Be Implemented in Our Practice Today? A Systematic Review of the Literature.

Eur Urol Oncol 2021 Feb 3;4(1):22-41. Epub 2021 Jan 3.

European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Working Group; Department of Urology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Context: The epidemiological signature of renal cell carcinoma (RCC) during the past decades is explained by overdetection and overtreatment of indolent cancers; furthermore, a non-negligible proportion of patients undergoing surgery for suspected RCC harbour benign renal tumours. As the gold standard for RCC diagnosis remains histopathological analysis of surgical or biopsy specimens, implementation of noninvasive diagnostic strategies to discriminate between benign and malignant renal masses is an urgent unmet need.

Objective: To systematically review novel liquid biomarkers and imaging modalities for RCC diagnosis.

Evidence Acquisition: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42020190773) using the MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUADAS 2 tool.

Evidence Synthesis: Overall, 15 studies (six on biomarkers and nine on imaging) and eight clinical trials were included. None of the biomarkers or imaging modalities has been validated or shown to have a distinct clinical value for RCC. Specific combinations of urinary cell-free and exosomal miRNAs, urinary miR-15a, and specific panels of urinary metabolites assessed by metabolomics appear promising. In addition, machine/deep learning algorithms and radiomics applied to cross-sectional images may have potential to improve RCC diagnosis. Most studies are limited by the retrospective design, size, and lack of external validation.

Conclusions: Liquid biomarkers or imaging modalities are not ready for integration in the clinic and further well-designed studies must validate preliminary findings and explore utility in clinical decision-making.

Patient Summary: We provide a comprehensive overview of the currently available biomarkers (measured in blood or urine) and novel imaging tests (other than conventional imaging) to discriminate kidney cancer from benign renal masses in a noninvasive fashion. None of the biomarkers or imaging modalities studied was validated or added clinical value; therefore, none of them can be implemented in the clinic. However, these approaches appear to be promising for improving the diagnosis of kidney cancer in the future.
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http://dx.doi.org/10.1016/j.euo.2020.12.011DOI Listing
February 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Quantifying the "Assistant Effect" in Robotic-Assisted Radical Prostatectomy (RARP): Measures of Technical Performance.

J Surg Res 2021 Apr 25;260:307-314. Epub 2020 Dec 25.

Division of Urology, Department of Surgery, University of Toronto, Toronto, Canada; International Centre for Surgical Safety, St. Michael's Hospital, Toronto, Canada. Electronic address:

Purpose: Surgeons are reliant on the bedside assistant during robotic surgeries. Using a modified global rating scale (GRS), we aim to assess the association between an assistant's technical skill on surgeon performance in Robotic-Assisted Radical Prostatectomy (RARP).

Methods: Prospective, intraoperative video from RARP cases at three centers were collected. Baseline demographic and RARP-experience data were collected from participating surgeons and trainees. The dissection of the prostatic pedicle and neurovascular bundle step (NVB) was analyzed. Expert analysts scored the console surgeon performance using the Global Evaluative Assessment of Robotic Skills (GEARS), and the bedside assistant performance using a modified Objective Structured Assessment of Technical Skills (aOSATS). The primary outcome is the association between console surgeon performance, as measured by GEARS, and assistant skill, as measured by aOSATS. Spearman's rho correlations were used to test the relationship between assistant and surgeon technical performance, and a multivariable linear regression model was created to test this association while controlling for patient factors.

Results: 92 RARP cases were available for the analysis, comprising 14 console surgeons and 22 different bedside assistants. In only 5 (5.4%) cases, the neurovascular bundle step was completed by a trainee, and in 13 (14.1%) of cases, a staff-level surgeon acted as the bedside assistant. aOSATS score was significantly associated with robotic console experience (P = 0.011), and prior laparoscopic experience (P < 0.001). Assistant aOSATS score showed a weak but significant correlation with surgeon GEARS score during the neurovascular bundle step (spearman's rho = 0.248, P = 0.028). On linear regression, aOSATS remained a significant predictor of console surgeon performance (P = 0.016), after controlling for patient age and BMI, prostate volume, tumor stage, and presence of nerve-sparing.

Conclusions: This is the first study to assess the association between assistant technical skill and surgeon performance in RARP. Additionally, we have provided validity evidence for a modified OSATS global rating scale for training and assessing bedside assistant performance.
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http://dx.doi.org/10.1016/j.jss.2020.11.037DOI Listing
April 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

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

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

JAMA Oncol 2020 12;6(12):1912-1920

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania.

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.

Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.

Design, Setting, And Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.

Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.

Main Outcomes And Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.

Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).

Conclusions And Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.
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http://dx.doi.org/10.1001/jamaoncol.2020.4922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582232PMC
December 2020

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

Creating patient-centered radiology reports to empower patients undergoing prostate magnetic resonance imaging.

Can Urol Assoc J 2021 Apr;15(4):108-113

Joint Department of Medical Imaging, Sinai Health System, University of Toronto, Toronto, ON, Canada.

Introduction: As we progress to an era when patient autonomy and shared decision-making are highly valued, there is a need to also have effective patient-centered communication tools. Radiology reports are designed for clinicians and can be very technical and difficult for patients to understand. It is important for patients to understand their magnetic resonance imaging (MRI) report in order to make an informed treatment decision with their physician. Therefore, we aimed to create a patient-centered prostate MRI report to give our patients a better understanding of their clinical condition.

Methods: A prototype patient-centered radiology report (PACERR) was created by identifying items to include based on opinions sought from a group of patients undergoing prostate MRI and medical experts. Data was collected in semi-structured interviews using a salient belief question. A prototype PACERR was created in collaboration with human factors engineering and design, medical imaging, biomedical informatics, and cancer patient education groups.

Results: Fifteen patients and eight experts from urology, radiation oncology, radiology, and nursing participated in this study. Patients were particularly interested to have a report with laymen terms, concise language, contextualization of values, definitions of medical terms, and next course of action. Everyone believed the report should include the risk of MRI findings actually being cancer in the subsequent biopsy.

Conclusions: A prostate MRI PACERR has been developed to communicate the most important findings relevant to decision-making in prostate cancer using patient-oriented design principles. The ability of this tool to improve patient knowledge and communication will be explored.
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http://dx.doi.org/10.5489/cuaj.6585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021434PMC
April 2021

Reply by Authors.

J Urol 2020 12 24;204(6):1194. Epub 2020 Sep 24.

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1097/JU.0000000000001157.02DOI Listing
December 2020

Functional genomic landscape of cancer-intrinsic evasion of killing by T cells.

Nature 2020 10 23;586(7827):120-126. Epub 2020 Sep 23.

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.

The genetic circuits that allow cancer cells to evade destruction by the host immune system remain poorly understood. Here, to identify a phenotypically robust core set of genes and pathways that enable cancer cells to evade killing mediated by cytotoxic T lymphocytes (CTLs), we performed genome-wide CRISPR screens across a panel of genetically diverse mouse cancer cell lines that were cultured in the presence of CTLs. We identify a core set of 182 genes across these mouse cancer models, the individual perturbation of which increases either the sensitivity or the resistance of cancer cells to CTL-mediated toxicity. Systematic exploration of our dataset using genetic co-similarity reveals the hierarchical and coordinated manner in which genes and pathways act in cancer cells to orchestrate their evasion of CTLs, and shows that discrete functional modules that control the interferon response and tumour necrosis factor (TNF)-induced cytotoxicity are dominant sub-phenotypes. Our data establish a central role for genes that were previously identified as negative regulators of the type-II interferon response (for example, Ptpn2, Socs1 and Adar1) in mediating CTL evasion, and show that the lipid-droplet-related gene Fitm2 is required for maintaining cell fitness after exposure to interferon-γ (IFNγ). In addition, we identify the autophagy pathway as a conserved mediator of the evasion of CTLs by cancer cells, and show that this pathway is required to resist cytotoxicity induced by the cytokines IFNγ and TNF. Through the mapping of cytokine- and CTL-based genetic interactions, together with in vivo CRISPR screens, we show how the pleiotropic effects of autophagy control cancer-cell-intrinsic evasion of killing by CTLs and we highlight the importance of these effects within the tumour microenvironment. Collectively, these data expand our knowledge of the genetic circuits that are involved in the evasion of the immune system by cancer cells, and highlight genetic interactions that contribute to phenotypes associated with escape from killing by CTLs.
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http://dx.doi.org/10.1038/s41586-020-2746-2DOI Listing
October 2020
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