Publications by authors named "Laurence Klotz"

419 Publications

Active surveillance in favorable intermediate-risk prostate cancer patients: Predictors of deferred intervention and treatment choice.

Can Urol Assoc J 2021 Aug 26. Epub 2021 Aug 26.

Section of Urology, Department of Surgery, Medical College of Georgia-Augusta University, Augusta, GA, United States.

Introduction: Active surveillance (AS) is increasingly used for favorable intermediate-risk (FIR) prostate cancer (PCa). Our objective was to determine oncological and sociodemographic predictors of deferred definitive therapy and decision for radical prostatectomy (RP) vs. radiotherapy (XRT).

Methods: The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database was used to identify all FIR PCa diagnosed between 2010 and 2015 opting for AS for at least one year following diagnosis. We sought to determine predictors of treatment and treatment type using multivariable logistic regression.

Results: A total of 20 334 patients were identified. An annual decrease in incident FIR patients managed initially with AS between 2010 (4061) and 2015 (2947) was noted (p for trend <0.001); 17 895 (88.0%) patients underwent deferred RP and/or XRT. Patients with higher baseline cancer volume and clinical stage were significantly more likely to discontinue AS. Patients of higher socioeconomic status were more likely to undergo deferred therapy, with increased odds for XRT over RP. African American patients had lower odds of undergoing definitive intervention (odds ratio 0.83, p=0.030) and were significantly more likely to opt for XRT. Oncological characteristics leading to FIR classification influenced treatment choice at the time of deferred intervention: XRT was treatment of choice in 86.3% and 86.0% of Gleason group 2 and PSA 10-20 FIR patients, respectively; 96.1% of treated cT2b-c FIR patients opted for RP.

Conclusions: Most FIR PCa patients initially managed with AS eventually undergo deferred definitive therapy, with choice of treatment significantly influenced by patients' baseline oncological and sociodemographic characteristics.
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http://dx.doi.org/10.5489/cuaj.7272DOI Listing
August 2021

Re: Jeremy Yeun-Chun Teoh, Daniele Castellani, Claudia Mercader, et al. A Quantitative Analysis Investigating the Prevalence of "Manels" in Major Urology Meetings. Eur Urol 2021;80:442-9.

Authors:
Laurence Klotz

Eur Urol 2021 Oct 13;80(4):e100. Epub 2021 Aug 13.

Department of Urology, University of Toronto, Toronto, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.07.003DOI Listing
October 2021

Reply by Authors.

J Urol 2021 Nov 12;206(5):1176. Epub 2021 Aug 12.

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

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http://dx.doi.org/10.1097/JU.0000000000001946.03DOI Listing
November 2021

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

J Urol 2021 Nov 29;206(5):1166-1176. 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.

Materials And Methods: Patients from the continuous androgen deprivation 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 >1.7 nmol/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 >0.7 nmol/l in the first year of therapy was associated with subsequent rises >1.7 nmol/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 followup, breakthrough testosterone was unrelated to time to CRPC, CSS or OS. Castrate testosterone values during ADT for recurrent prostate cancer provides prognostic information that 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
November 2021

Not So "Active" Surveillance.

Int J Radiat Oncol Biol Phys 2021 07;110(3):716-717

Section of Urology, Department of Surgery, Medical College of Georgia-Augusta University, Georgia Cancer Center, Augusta, Georgia.

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http://dx.doi.org/10.1016/j.ijrobp.2021.01.030DOI Listing
July 2021

Incidental Prostate Cancer (cT1a-cT1b) Is a Relevant Clinical and Research Entity and Should Be Fully Discussed in the International Prostate Cancer Guidelines.

Eur Urol Oncol 2021 Apr 1. Epub 2021 Apr 1.

Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy; Division of Experimental Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.euo.2021.03.005DOI Listing
April 2021

The 'C' Words: parallels and analogies between Prostate Cancer and Covid-19.

World J Urol 2021 Sep 11;39(9):3175-3176. Epub 2021 Mar 11.

Department of Surgery/Urologic Oncology, McMaster University, Hamilton, Canada.

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http://dx.doi.org/10.1007/s00345-021-03627-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946615PMC
September 2021

Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: Recommendations of an international Delphi consensus.

Urol Oncol 2021 Mar 3. Epub 2021 Mar 3.

Division of Urology, Duke University Medical Center, Durham, NC. Electronic address:

Background: With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS).

Methods: A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement.

Results: Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community.

Conclusions: FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.027DOI Listing
March 2021

Liproca Depot: A New Antiandrogen Treatment for Active Surveillance Patients.

Eur Urol Focus 2021 Feb 12. Epub 2021 Feb 12.

Tampere University Hospital and Tampere University, Tampere, Finland.

Background: There is increasing interest in nonmorbid treatments for low- and intermediate-risk prostate cancer with fewer side effects than surgery or radiotherapy.

Objective: To investigate the tolerability, safety, and antitumor effects of the intraprostatic NanoZolid depot formulation Liproca Depot (LIDDS AB, Uppsala, Sweden) with antiandrogen 2-hydroxyflutamide (2-HOF) in men with low- or intermediate-risk localized prostate cancer managed with active surveillance.

Design, Setting, And Participants: This clinical phase 2b trial, LPC-004, involved 61 patients. The 2-HOF-containing formulation Liproca Depot was injected transrectally into the prostate under ultrasound guidance. A single dose of 35% or 45% of the prostate volume (study part 1) and a fixed dose of 16 or 20 ml (study part 2) of the formulation were evaluated.

Outcome Measurements And Statistical Analyses: The primary endpoints were tolerability and the reduction in serum prostate-specific antigen (PSA) 5 mo after injection. Antitumor effects were evaluated with magnetic resonance imaging (MRI) and prostate biopsies. Quality of life was assessed using a validated questionnaire (International Prostate Symptom Score).

Results And Limitations: All doses were safe and well tolerated, without hormonal side effects. In part 2 of the study, the PSA reduction was greatest for the group receiving 16 ml, with an average decrease of 14%, and 95% of patients had a PSA reduction. Some 78% of patients showed a prostate volume decrease compared to baseline. Prostate MRI and biopsies confirmed stable or reduced lesion size. However, post treatment biopsies were performed at the discretion of the investigator, and not routinely. Most patients were amenable to a second injection.

Conclusions: PSA and prostate volume decreased in most patients. Indications of efficacy were shown by post-treatment MRI and biopsies demonstrating stabilization or regression in the majority of cases.

Patient Summary: Liproca Depot is a safe, minimally invasive treatment that offers the potential for cancer control in patients with intermediate-risk prostate cancer. Further clinical evaluation is warranted.
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http://dx.doi.org/10.1016/j.euf.2021.02.003DOI Listing
February 2021

Influence of Sociodemographic Factors on Definitive Intervention Among Low-risk Active Surveillance Patients.

Urology 2021 Sep 10;155:117-123. Epub 2021 Feb 10.

Section of Urology, Department of Surgery, Medical College of Georgia-Augusta University, Augusta, GA; Georgia Cancer Center, Augusta, GA. Electronic address:

Objectives: To investigate sociodemographic factors influencing decision of initially active surveillance (AS) prostate cancer (CaP) patients to opt for definitive therapy, and, specifically, choice of radical prostatectomy (RP) versus radiation therapy (XRT).

Methods: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Watchful Waiting database was used to identify AS patients diagnosed with NCCN low-risk CaP between 2010 and 2015. We sought to determine predictors of treatment type using multivariable logistic regression analyses.

Results: Out of 32,874 men included, 21,255 (64.7%) underwent delayed treatment, with 3,751 (17.6%) and 17,463 (82.2%) opting for RP and XRT, respectively. Patients who were married (Odds Ratio [OR]: 1.18, P <.001), insured (OR 2.94, P <.001), of higher socioeconomic status (OR 1.67 for highest vs lowest, P <.01), and residing in a Southeastern or Midwestern region (ORs 1.26 and 1.22 vs Northeast, respectively, P <.01) were significantly more likely to undergo definitive intervention. A significant interaction between patient race and marital/socioeconomic statuses on the decision-making process was identified. Decision for XRT (vs RP) was more likely in older (OR 11.6 for 70-79 vs 50-59 years, P <.01), unmarried (OR 1.89, P <.01), African American (OR 1.41, P .018), and higher socioeconomic status (OR 1.54 for highest versus lowest quartile, P <.01) patients.

Conclusion: The majority of patients initially treated with AS underwent delayed treatment. After accounting for pathologic characteristics, the interaction of sociodemographic factors including race, socioeconomic status, marital status, insurance status, and region of residence are significantly associated with the likelihood of undergoing definitive therapy.
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http://dx.doi.org/10.1016/j.urology.2021.01.053DOI Listing
September 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

Overdiagnosis in urologic cancer : For World Journal of Urology Symposium on active surveillance in prostate and renal cancer.

Authors:
Laurence Klotz

World J Urol 2021 Jan 25. Epub 2021 Jan 25.

Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. #MG408, Toronto, ON, M4N 3M5, Canada.

Background: Cancer, which historically was diagnosed at late and incurable stages, has expanded to a heterogeneous group of conditions that vary from clinically insignificant to rapidly aggressive and lethal. This evolution is due to the widespread use of screening tests for early detection of cancer, both directed (i.e., PSA, mammography, colonoscopy) and undirected (abdominal imaging). The use of these tests has resulted in both benefits and harms. The benefits are a reduction in survival and mortality, due to significant cancers being diagnosed at a more curable stage. The harms are an increase, in some cases dramatic, in the diagnosis of clinically insignificant disease. These are called 'cancer' but not destined to affect the patient's life, even in the absence of treatment.

Methods: Non-explicit summary of the literature on overdiagnosis of cancer.

Results: The phenomenon of overdiagnosis requires two factors: the presence of a common reservoir of microfocal disease and a screening test to find it. These factors exist for breast, prostate, skin, renal, and thyroid cancers, and to a lesser degree for lung cancer. The problem of cancer overdiagnosis and overtreatment is complex, with numerous etiologies and many tradeoffs. It is a particular problem in prostate cancer but is a major issue in many other cancer sites. Screening for prostate cancer based on the best data from prospective randomized trials significantly reduces cancer mortality. However, reducing overtreatment in patients diagnosed with indolent disease is critical to the success of screening.

Conclusion: Active surveillance, the focus of this series of articles, is an important strategy to reduce overtreatment. This article reviews the pathological, clinical, social, and psychological aspects of overdiagnosis in cancer.
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http://dx.doi.org/10.1007/s00345-020-03523-2DOI Listing
January 2021

THE CARDIOVASCULAR EFFECTS OF GNRH ANTAGONISTS IN MEN WITH PROSTATE CANCER.

Eur Heart J Cardiovasc Pharmacother 2021 Jan 20. Epub 2021 Jan 20.

Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Canada.

Aims: The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.

Methods And Results: We conducted a systematic review to identify all randomised, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified ten eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83) respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.

Conclusions: There is consistent but methodologically limited data to suggest that GnRH antagonists - a relatively new class of androgen deprivation therapy for prostate cancer - cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.
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http://dx.doi.org/10.1093/ehjcvp/pvab005DOI Listing
January 2021

The Association Between Statin Use and Outcomes in Patients Initiating Androgen Deprivation Therapy.

Eur Urol 2021 04 31;79(4):446-452. Epub 2020 Dec 31.

Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Background: Studies have conflicting results regarding the association between statin use and biochemical recurrence for prostate cancer (PCa). A limited number of studies examining statins in advanced stages report positive results, with a few specifically examining statins and androgen deprivation therapy (ADT).

Objective: To perform a post hoc secondary analysis of a randomised controlled trial (RCT) of men initiating ADT to examine the association between statin use and outcomes.

Design, Setting, And Participants: Patients with prostate-specific antigen (PSA) >3 ng/ml >1 yr following primary/salvage radiotherapy were enrolled in an RCT of intermittent androgen deprivation (IAD) versus continuous ADT (NCT00003653). Baseline and on-study statin use was modelled as a time-dependent covariate.

Outcome Measurements And Statistical Analysis: The primary endpoint was overall survival. Models were adjusted for age, time from radiotherapy to ADT, baseline PSA, and prior ADT.

Results And Limitations: Of 1364 patients, statin users (585; 43%) were younger (72.7 vs 73.8 yr, p = 0.001) and less likely to have PSA >15 ng/ml (20% vs 25%, p = 0.04). After a median follow-up of 6.9 yr, statin use was associated with reduced overall (hazard ratio [HR]: 0.64; 95% confidence interval [CI] 0.53-0.78, p < 0.001) and PCa-specific (HR: 0.65, 95% CI 0.48-0.87, p = 0.004) mortality. Statin users had 13% longer time to castration resistance, but this did not reach statistical significance (p = 0.15). As an exploratory endpoint, in the IAD arm, statin users had longer time off treatment (median: 0.85 vs 0.64 yr, p = 0.06). Limitations include potential for residual confounding between statin users and nonusers, and confounding by indication.

Conclusions: In men treated with ADT following primary or salvage radiotherapy, statin use was associated with improved overall and PCa-specific survival. In patients treated with IAD, statin use was associated with a trend towards longer time off treatment. A prospective trial of statins in men commencing ADT is warranted.

Patient Summary: We found a favourable association between statin use and survival outcomes in patients initiating androgen deprivation therapy.
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http://dx.doi.org/10.1016/j.eururo.2020.12.031DOI Listing
April 2021

Psychological morbidity associated with prostate cancer: Rates and predictors of depression in the RADICAL PC study.

Can Urol Assoc J 2021 Jun;15(6):181-186

Department of Urology, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.

Introduction: Across all cancer sites and stages, prostate cancer has one of the greatest median five-year survival rates, highlighting the important focus on survivorship issues following diagnosis and treatment. In the current study, we sought to evaluate the prevalence and predictors of depression in a large, multicenter, contemporary, prospectively collected sample of men with prostate cancer.

Methods: Data from the current study were drawn from the baseline visit of men enrolled in the RADICAL PC study. Men with a new diagnosis of prostate cancer or patients initiating androgen deprivation therapy for prostate cancer for the first time were recruited. Depressive symptoms were evaluated using the nine-item version of the Patient Health Questionnaire (PHQ-9). To evaluate factors associated with depression, a multivariable logistic regression model was constructed, including biological, psychological, and social predictor variables.

Results: Data from 2445 patients were analyzed. Of these, 201 (8.2%) endorsed clinically significant depression. Younger age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.16-1.60 per 10-year decrease), being a current smoker (OR 2.77, 95% CI 1.66-4.58), former alcohol use (OR 2.63, 95% CI 1.33-5.20), poorer performance status (OR 5.01, 95% CI 3.49-7.20), having a pre-existing clinical diagnosis of depression or anxiety (OR 3.64, 95% CI 2.42-5.48), and having high-risk prostate cancer (OR 1.49, 95% CI 1.05-2.12) all conferred independent risk for depression.

Conclusions: Clinically significant depression is common in men with prostate cancer. Depression risk is associated with a host of biopsychosocial variables. Clinicians should be vigilant to screen for depression in those patients with poor social determinants of health, concomitant disability, and advanced disease.
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http://dx.doi.org/10.5489/cuaj.6912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195585PMC
June 2021

Current evidence for focal therapy and partial gland ablation for organ-confined prostate cancer: systematic review of literature published in the last 2 years.

Curr Opin Urol 2021 01;31(1):49-57

Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Purpose Of Review: The shift in the diagnostic algorithm for prostate cancer to early imaging with mpMRI has resulted in many patients being diagnosed with small volume, apparently unilateral, clinically significant cancers. In these patients, a minimally invasive, nonmorbid intervention is appealing. The aim of this study was to review data reported within the last 2 years on focal therapy and partial gland ablation for organ-confined prostate cancer.

Recent Findings: High-intensity focal ultrasound, focal cryotherapy, photodynamic therapy, irreversible electroporation and focal laser ablation, have been used as treatment modalities for localized prostate cancer treatment. The reported oncologic outcomes vary widely and makes comparisons challenging. All the focal therapies report low rates of complications, and high rates of continence and erectile function preservation. The most common adverse events are hematuria, urinary retention and urinary tract infections. During this period, the initial results of several new technologies including MRI-guided transurethral ultrasound ablation were published.

Summary: Focal therapy and partial gland ablation for organ-confined prostate cancer is an option for patients with intermediate-risk disease because of its low complication profile and preservation of QOL. Trials comparing the outcome of different focal therapy technologies have not been carried out, and the existing evidence does not point to one approach being clearly superior to others. Long-term oncologic outcome is lacking. Despite this, for men with unilateral intermediate-risk prostate cancer whose disease is often relatively indolent, focal therapy is an appealing option.
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http://dx.doi.org/10.1097/MOU.0000000000000838DOI Listing
January 2021

Trends in urologic oncology clinical practice and medical education under COVID-19 pandemic: An international survey of senior clinical and academic urologists.

Urol Oncol 2020 12 7;38(12):929.e1-929.e10. Epub 2020 Oct 7.

Department of Urology, Chaim Sheba Medical Center, Ramat Gan, Israel, The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Objective: Ad-hoc guidelines for managing the COVID-19 pandemic are published worldwide. We investigated international applications of such policies in the urologic-oncology community.

Methods: A 20-item survey was e-mailed via SurveyMonkey to 100 international senior urologic-oncology surgeons. Leaders' policies regarding clinical/surgical management and medical education were surveyed probing demographics, affiliations, urologic-oncologic areas of interest, and current transportation restrictions. Data on COVID-19 burden were retrieved from the ECDC. Statistical analyses employed non-parametric tests (SPSS v.25.0, IBM).

Results: Of 100 leaders from 17 countries, 63 responded to our survey, with 58 (92%) reporting university and/or cancer-center affiliations. Policies on new-patient visits remained mostly unchanged, while follow-up visits for low-risk diseases were mostly postponed, for example, 83.3% for small renal mass (SRM). Radical prostatectomy was delayed in 76.2% of cases, while maintaining scheduled timing for radical cystectomy (71.7%). Delays were longer in Europe than in the Americas for kidney cancer (SRM follow-up, P = 0.014), prostate cancer (new visits, P = 0.003), and intravesical therapy for intermediate-risk bladder cancer (P = 0.043). In Europe, COVID-19 burden correlated with policy adaptation, for example, nephrectomy delays for T2 disease (r = 0.5, P =0.005). Regarding education policies, trainees' medical education was mainly unchanged, whereas senior urologists' planned attendance at professional meetings dropped from 6 (IQR 1-11) to 2 (IQR 0-5) (P < 0.0001).

Conclusion: Under COVID-19, senior urologic-oncology surgeons worldwide apply risk-stratified approaches to timing of clinical and surgical schedules. Policies regarding trainee education were not significantly affected. We suggest establishment of an international consortium to create a directive for coping with such future challenges to global healthcare.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539173PMC
December 2020

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer.

J Urol 2021 Mar 6;205(3):769-779. Epub 2020 Oct 6.

University of Chicago.

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT).

Materials And Methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy.

Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05).

Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.
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http://dx.doi.org/10.1097/JU.0000000000001362DOI Listing
March 2021

When to biopsy Prostate Imaging and Data Reporting System version 2 (PI-RADSv2) assessment category 3 lesions? Use of clinical and imaging variables to predict cancer diagnosis at targeted biopsy.

Can Urol Assoc J 2021 Apr;15(4):115-121

Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Introduction: We aimed to determine if clinical and imaging features can stratify men at higher risk for clinically significant (CS, International Society of Urological Pathology [ISUP] grade group ≥2) prostate cancer (PCa) in equivocal Prostate Imaging and Data Reporting System (PI-RADS) category 3 lesions on magnetic resonance imaging (MRI).

Methods: Approved by the institutional review board, this retrospective study involved 184 men with 198 lesions who underwent 3T-MRI and MRI-directed transrectal ultrasound biopsy for PI-RADS 3 lesions. Men were evaluated including clinical stage, prostate-specific antigen density (PSAD), indication, and MRI lesion size. Diagnoses for all men and by indication (no cancer, any PCa, CSPCa) were compared using multivariate logistic regression, including stage, PSAD, and lesion size.

Results: We found an overall PCa rate of 31.8% (63/198) and 10.1% (20/198) CSPCa (13 grade group 2, five group 3, and two group 4). Higher stage (p=0.001), PSAD (p=0.007), and lesion size (p=0.015) were associated with CSPCa, with no association between CSPCa and age, PSA, or prostate volume (p>0.05). PSAD modestly predicted CSPCa area under the curve (AUC) 0.66 (95% confidence interval [CI] 0.518-0.794) in all men and 0.64 (0.487-0.799) for those on active surveillance (AS). Model combining clinical stage, PSAD, and lesion size improved accuracy for all men and AS (AUC 0.82 [0.736-0.910], p<0.001 and 0.785 [0.666-0.904], p<0.001). In men with prior negative biopsy and persistent suspicion, PSAD (0.90 [0.767-1.000]) was not different from the model (p>0.05), with optimal cutpoint of ≥0.215 ng/mL/cc achieving sensitivity/specificity of 85.7/84.4%.

Conclusions: PI-RADSv2 category 3 lesions are often not CSPCa. PSAD predicted CSPCa in men with a prior negative biopsy; however, PSAD alone had limited value, and accuracy improved when using a model incorporating PSAD with clinical stage and MRI lesion size.
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http://dx.doi.org/10.5489/cuaj.6781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021423PMC
April 2021

Patients' perspective of telephone visits during the COVID-19 pandemic.

Can Urol Assoc J 2020 Sep;14(9):E402-E406

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

Introduction: With the cessation of non-urgent clinical office visits due to the coronavirus, there has been a rapid shift to telephone and other virtual visits in outpatient practice. We conducted a survey to evaluate patients' perspective of telephone visits during the COVID-19 pandemic.

Methods: Patients receiving a scheduled telephone call as a virtual visit from urologists at our clinic were asked to participate in a three-minute, self-administered, online questionnaire. After verbal permission was obtained, the survey was emailed to each participant. The outcomes evaluated were telephone visit satisfaction and preference for type of appointment. Non-parametric tests were used to analyze the results. The study was approved by the Sunnybrook Research Ethics Board.

Results: A total of 102 participants were included; 96% of participants assessed the telephone visit as a positive experience in every survey question, while 45% expressed no preference. In those who expressed a preference, this was evenly divided between in-office visits and phone visits (p=0.0614). Participants who lived more than 75 km from the hospital were less likely to prefer an in-office visit compared to those residing locally (U=433, p=0.006; odds ratio 0.29, 95% confidence interval 0.106-0.779, p=0.0142).

Conclusions: In this survey, most participants assessed the telephone visit positively. Almost half had no preference and a similar proportion expressed a preference for in-office and telephone visits. Patients who resided farther from the hospital were more likely to prefer the telephone visit. This is the first study that we know of to assess patients' preferences regarding remote encounters in urology.
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http://dx.doi.org/10.5489/cuaj.6758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492037PMC
September 2020

Scoping review: hotspots for COVID-19 urological research: what is being published and from where?

World J Urol 2021 Sep 9;39(9):3151-3160. Epub 2020 Sep 9.

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

Purpose: Contemporary, original research should be utilised to inform guidelines in urology relating to the COVID-19 pandemic. This comprehensive review aimed to: identify all up-to-date original publications relating to urology and COVID-19, characterise where publications were from, and outline what topics were investigated.

Methods: This review utilised a search strategy that assessed five electronic databases, additional grey literature, and global trial registries. All current published, in-press, and pre-print manuscripts were included. Eligible studies were required to be original research articles of any study design, reporting on COVID-19 or urology, in any of study population, intervention, comparison, or outcomes. Included studies were reported in a narrative synthesis format. Data were summarised according to primary reported outcome topic. A world heatmap was generated to represent where included studies originated from.

Results: Of the 6617 search results, 48 studies met final inclusion criteria, including 8 pre-prints and 7 ongoing studies from online registries. These studies originated from ten countries according to first author affiliation. Most studies originated from China (n = 13), followed by Italy (n = 12) and USA (n = 11). Topics of the study included pathophysiological, administrative, and clinical fields: translational (n = 14), COVID-19-related outcomes (n = 5), urology training (n = 4), telemedicine (n = 7), equipment and safety (n = 2), urology in general (n = 4), uro-oncology (n = 3), urolithiasis (n = 1), and kidney transplantation (n = 8).

Conclusion: This review has outlined available original research relevant to COVID-19 and urology from the international community. This summary may serve as a guide for future research priorities in this area.
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http://dx.doi.org/10.1007/s00345-020-03434-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480207PMC
September 2021

Impact of COVID-19 on medical education: introducing homo digitalis.

World J Urol 2021 Jun 29;39(6):1997-2003. Epub 2020 Aug 29.

Department of Urology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Purpose: To determine how members of the Société Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19.

Methods: A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents.

Results: In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; all ps < 0.001), followed by searching journals and textbook including the online versions (62%; all ps < 0.001). Overall, 6% of the respondents reported no time/interest for CME during the pandemic. Although most urologists report using only one platform for their CME (26.6%), the majority reported using ≥ 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice.

Conclusion: During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods.
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http://dx.doi.org/10.1007/s00345-020-03417-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455506PMC
June 2021

Active surveillance for low-risk prostate cancer - in pursuit of a standardized protocol.

Cent European J Urol 2020 25;73(2):123-126. Epub 2020 Jun 25.

Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Introduction: Active surveillance (AS) is a management option recommended by most guidelines for low risk clinically-localized prostate cancer (LR-CLPC). Data shows that AS is being increasingly adopted into clinical practice worldwide. Our aim was to review the up-to date guidelines and observational studies in regards to AS in LR-CLRPC to gain insight into principles of contemporary clinical practice.

Material And Methods: Several guidelines on the management of low-risk prostate cancer were reviewed for evidence-based recommendations regarding the protocol of AS. We reviewed the available literature for most recent studies on AS in LR-CLPC.

Results: No uniform protocol of AS in LR-CLPC has been recommended up to date and available guidelines significantly differ in terms of protocol schedules and the role of particular tools in monitoring for disease progression. Nevertheless, recent studies on AS in LR-CLPC, in which various protocols were adopted, have demonstrated promising outcomes in regards to cancer-specific survival (99-100% at 5 years, 98.1-99.9% at 10 years, and 94.3-96% at 15 years), with high rates of men remaining within the protocols (23-39% at 10 years).

Conclusions: This article is a call for focusing further research on development and recommending a precise and standardized, evidence-based protocol for AS in LR-CLPC.
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http://dx.doi.org/10.5173/ceju.2020.0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407781PMC
June 2020

Outreach and Influence of Surgical Societies' Recommendations on Minimally Invasive Surgery During the COVID-19 Pandemic-An Anonymized International Urologic Expert Inquiry.

Urology 2020 11 8;145:73-78. Epub 2020 Aug 8.

Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany. Electronic address:

Objective: To assess the outreach and influence of the main recommendations of surgical governing bodies on adaptation of minimally invasive laparoscopic surgery (MIS) procedures during the coronavirus disease 2019 (COVID-19) pandemic in an anonymized multi-institutional survey.

Materials And Methods: International experts performing MIS were selected on the basis of the contact database of the speakers of the Friends of Israel Urology Symposium. A 24-item questionnaire was built using main recommendations of surgical societies. Total cases/1 Mio residents as well as absolute number of total cases were utilized as surrogates for the national disease burden. Statistics and plots were performed using RStudio v0.98.953.

Results: Sixty-two complete questionnaires from individual centers performing MIS were received. The study demonstrated that most centers were aware of and adapted their MIS management to the COVID-19 pandemic in accordance to surgical bodies' recommendations. Hospitals from the countries with a high disease burden put these adoptions more often into practice than the others particularly regarding swabs as well as CO2 insufflation and specimen extraction procedures. Twelve respondents reported on presumed severe acute respiratory syndrome coronavirus 2 transmission during MIS generating hypothesis for further research.

Conclusion: Guidelines of surgical governing bodies on adaptation of MIS during the COVID-19 pandemic demonstrate significant outreach and implementation, whereas centers from the countries with a high disease burden are more often poised to modify their practice. Rapid publication and distribution of such recommendation is crucial during future epidemic threats.
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http://dx.doi.org/10.1016/j.urology.2020.07.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414774PMC
November 2020

Cross-continental comparison of safety and protection measures amongst urologists during COVID-19.

Int J Urol 2020 11 8;27(11):981-989. Epub 2020 Aug 8.

Department of Urology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Objectives: To determine the well-being of urologists worldwide during the coronavirus disease 2019 pandemic, and whether they have adequate personal protective equipment knowledge and supplies appropriate to their clinical setting.

Methods: Urologists worldwide completed a Société Internationale d'Urologie online survey from 16 April 2020 until 1 May 2020. Analysis was carried out to evaluate their knowledge about protecting themselves and others in the workplace, including their confidence in their ability to remain safe at work, and any regional differences.

Results: There were 3488 respondents from 109 countries. Urologists who stated they were moderately comfortable that their work environment offers good protection against coronavirus disease 2019 showed a total mean satisfaction level of 5.99 (on a "0 = not at all" to "10 = very" scale). A large majority (86.33%) were confident about protecting themselves from coronavirus disease 2019 at work. However, only about one-third reported their institution provided the required personal protective equipment (35.78%), and nearly half indicated their hospital has or had limited personal protective equipment availability (48.08%). Worldwide, a large majority of respondents answered affirmatively for testing the healthcare team (83.09%). Approximately half of the respondents (52.85%) across all regions indicated that all surgical team members face an equal risk of contracting coronavirus disease 2019 (52.85%). Nearly one-third of respondents reported that they had experienced social avoidance (28.97%).

Conclusions: Our results show that urologists lack up-to-date knowledge of preferred protocols for personal protective equipment selection and use, social distancing, and coronavirus disease 2019 testing. These data can provide insights into functional domains from which other specialties could also benefit.
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http://dx.doi.org/10.1111/iju.14340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436488PMC
November 2020

Moving away from systematic biopsies: image-guided prostate biopsy (in-bore biopsy, cognitive fusion biopsy, MRUS fusion biopsy) -literature review.

World J Urol 2021 Mar 29;39(3):677-686. Epub 2020 Jul 29.

Department of Urology, Istanbul Medipol University, Istanbul, Turkey.

Objective: To compare the detection rate of clinically significant cancer (CSCa) by magnetic resonance imaging-targeted biopsy (MRI-TB) with that by standard systematic biopsy (SB) and to evaluate the role of MRI-TB as a replacement from SB in men at clinical risk of prostate cancer.

Methods: The non-systematic literature was searched for peer-reviewed English-language articles using PubMed, including the prospective paired studies, where the index test was MRI-TB and the comparator text was SB. Also the randomized clinical trials (RCTs) are included if one arm was MRI-TB and another arm was SB.

Results: Eighteen prospective studies used both MRI-TB and TRUS-SB, and eight RCT received one of the tests for prostate cancer detection. In most prospective trials to compare MRI-TB vs. SB, there was no significant difference in any cancer detection rate; however, MRI-TB detected more men with CSCa and fewer men with CISCa than SB.

Conclusion: MRI-TB is superior to SB in detection of CSCa. Since some significant cancer was detected by SB only, a combination of SB with the TB technique would avoid the underdiagnosis of CSCa.
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http://dx.doi.org/10.1007/s00345-020-03366-xDOI Listing
March 2021

Comparison of micro-ultrasound and multiparametric magnetic resonance imaging for prostate cancer: A multicenter, prospective analysis.

Can Urol Assoc J 2021 Jan;15(1):E11-E16

Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, United States.

Introduction: High-resolution micro-ultrasound has the capability of imaging prostate cancer based on detecting alterations in ductal anatomy, analogous to multiparametric magnetic resonance imaging (mpMRI). This technology has the potential advantages of relatively low cost, simplicity, and accessibility compared to mpMRI. This multicenter, prospective registry aims to compare the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mpMRI with high-resolution micro-ultrasound imaging for the detection of clinically significant prostate cancer.

Methods: We included 1040 subjects at 11 sites in seven countries who had prior mpMRI and underwent ExactVu micro-ultrasound-guided biopsy. Biopsies were taken from both mpMRI targets (Prostate Imaging-Reporting and Data System [PI-RADS] >3 and micro-ultrasound targets (Prostate Risk Identification using Micro-ultrasound [PRIMUS] >3). Systematic biopsies (up to 14 cores) were also performed. Various strategies were used for mpMRI target sampling, including cognitive fusion with micro-ultrasound, separate software-fusion systems, and software-fusion using the micro-ultrasound FusionVu system. Clinically significant cancer was those with Gleason grade group ≥2.

Results: Overall, 39.5% were positive for clinically significant prostate cancer. Micro-ultrasound and mpMRI sensitivity was 94% vs. 90%, respectively (p=0.03), and NPV was 85% vs. 77%, respectively. Specificities of micro-ultrasound and MRI were both 22%, with similar PPV (44% vs. 43%). This represents the initial experience with the technology at most of the participating sites and, therefore, incorporates a learning curve. Number of cores, diagnostic strategy, blinding to MRI results, and experience varied between sites.

Conclusions: In this initial multicenter registry, micro-ultrasound had comparable or higher sensitivity for clinically significant prostate cancer compared to mpMRI, with similar specificity. Micro-ultrasound is a low-cost, single-session option for prostate screening and targeted biopsy. Further larger-scale studies are required for validation of these findings.
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http://dx.doi.org/10.5489/cuaj.6712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769516PMC
January 2021
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