Publications by authors named "Alejandro Berlin"

92 Publications

Detection of clinically significant prostate cancer with F-DCFPyL PET/multiparametric MR.

Eur J Nucl Med Mol Imaging 2021 Apr 12. Epub 2021 Apr 12.

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital & Women's College Hospital, University of Toronto, 610 University Ave, Suite 3-920, Toronto, ON, M5G 2M9, Canada.

Purpose: To assess whether F-DCFPyL PET/multiparametric (mp)MR contributes to the diagnosis of clinically significant (cs) prostate cancer (PCa) compared to mpMR in patients with suspicion of PCa, or patients being considered for focal ablative therapies (FT).

Patients And Methods: This ethics review board-approved, prospective study included 55 men with suspicion of PCa and negative systematic biopsies or clinically discordant low-risk PCa (n = 21) or those being considered for FT (n = 34) who received F-DCFPyL PET/mpMR. Each modality, PET, mpMR, and PET/MR (using the PROMISE classification), was assessed independently. All suspicious lesions underwent PET/MR-ultrasound fusion biopsies.

Results: There were 45/55 patients (81.8%) that had histologically proven PCa and 41/55 (74.5%) were diagnosed with csPCa. Overall, 61/114 lesions (53.5%) identified on any modality were malignant; 49/61 lesions (80.3%) were csPCa. On lesion-level analysis, for detection of csPCa, the sensitivity of PET was higher than that of mpMR and PET/MR (86% vs 67% and 69% [p = 0.027 and 0.041, respectively]), but at a lower specificity (32% vs 85% and 86%, respectively [p < 0.001]). The performance of MR and PET/MR was comparable. For identification of csPCa in PI-RADS ≥ 3 lesions, the AUC (95% CI) for PET, mpMR, and PET/MR was 0.75 (0.65-0.86), 0.69 (0.56-0.82), and 0.78 (0.67-0.89), respectively. The AUC for PET/MR was significantly larger than that of mpMR (p = 0.04).

Conclusion: PSMA PET detects more csPCa than mpMR, but at low specificity. The performance PET/MR is better than mpMR for detection of csPCa in PI-RADS ≥ 3 lesions.

Clinical Registration: NCT03149861.
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http://dx.doi.org/10.1007/s00259-021-05355-7DOI Listing
April 2021

Impact of EGFR mutation on outcomes following SRS for brain metastases in non-small cell lung cancer.

Lung Cancer 2021 Mar 2;155:34-39. Epub 2021 Mar 2.

Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Introduction: Patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) are at particularly high risk of developing brain metastases (BrM). In addition to EGFR targeting tyrosine kinase inhibitors (TKI), radiosurgery (SRS) has an important role in the management of EGFRm BrM. However, data specific to the response and toxicity of EGFRm BrM to SRS are sparse. We evaluated the incidence of local failure (LF) and toxicity of EGFRm and EGFR-wild-type (EGFRwt) BrM treated with SRS.

Methods: We analyzed a prospective registry of BrM patients treated at our centre between 2008 and 2017 and identified EGFRm and EGFRwt NSCLC patients treated with SRS ± systemic therapy for BrM. Incidences of local failure (LF) and radionecrosis (RN) were determined, and Cox regression was performed for univariate and multivariate analyses (MVAs).

Results: We analyzed data from 218 patients (615 lesions - 225 EGFRm and 390 EGFRwt). Median imaging follow-up per patient was 14.5 months (0.5-96.3). Prior to or concomitant with SRS, 62 % of EGFRm patients received TKI and 93 % received TKI post SRS. The 24-month incidence of LF was 6% and 16 % for EGFRm BrM and EGFRwt, respectively (0.43(0.19-0.95); p = 0.037). The 24-month incidence of RN was 4% and 6% for EGFRm and EGFRwt BrM, respectively (0.8(0.32-1.98) p = 0.63). On MVA, BrM size and prescription dose (PD) significantly correlated with a higher risk of LF and BrM size correlated with a higher risk of RN.

Conclusion: We observed excellent rates of response and toxicity following SRS in EGFRm compared to EGFRwt NSCLC, suggesting that EGFRm BrM have a favourable risk benefit ratio compared to EGFRwt NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2021.02.036DOI 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

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of F-DCFPyL PET/CT Restaging.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100553. Epub 2020 Sep 9.

Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre and Western University, London, Canada.

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy.

Methods And Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT.

Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months.

Conclusions: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.
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http://dx.doi.org/10.1016/j.adro.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820022PMC
September 2020

Clinicopathologic and Treatment Features of Long-Term Surviving Brain Metastasis Patients.

Curr Oncol 2021 Jan 18;28(1):549-559. Epub 2021 Jan 18.

Department of Radiation Oncology, University of Toronto, Toronto, ON M5G2M9, Canada.

Background: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS).

Methods: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived ≥ 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method.

Results: Median follow up for LTS was 67 months (range 36-181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively.

Conclusion: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.
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http://dx.doi.org/10.3390/curroncol28010054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903267PMC
January 2021

Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression.

Nat Cell Biol 2021 01 8;23(1):87-98. Epub 2021 Jan 8.

Department of Urology, Shanghai Changhai Hospital, Shanghai, P. R. China.

Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.
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http://dx.doi.org/10.1038/s41556-020-00613-6DOI Listing
January 2021

The Mutational Landscape of Metastatic Castration-sensitive Prostate Cancer: The Spectrum Theory Revisited.

Eur Urol 2021 Jan 5. Epub 2021 Jan 5.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Emerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical.

Objective: To characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC.

Design, Setting, And Participants: This was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease.

Outcome Measurements And Statistical Analysis: We measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC).

Results And Limitations: The frequency of driver mutations in TP53 (p =  0.01), WNT (p =  0.08), and cell cycle (p =  0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p =  0.002), and time to CRPC (95.6 vs 155.8 mo; p =  0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p =  0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p =  0.004) and DNA double-strand break repair (IRR 1.61; p <  0.001) were associated with a higher number of metastases. Mutations in TP53 were also independently associated with shorter rPFS (hazard ratio [HR] 1.59; p =  0.03) and the development of CRPC (HR 1.71; p =  0.01) on multivariable analysis. This study was limited by its retrospective nature, sample size, and the use of commercially available sequencing platforms, resulting in a limited predefined set of genes examined.

Conclusions: Somatic mutational profiles reveal a spectrum of metastatic biology that helps in redefining oligometastasis beyond a simple binary state of lesion enumeration.

Patient Summary: Oligometastatic prostate cancer is typically defined as less than three to five metastatic lesions and evidence suggests that using radiation or surgery to treat these sites improves clinical outcomes. As of now, treatment decisions for oligometastasis are solely defined according to the number of lesions. However, this study suggests that tumor mutational profiles can provide a biological definition of oligometastasis and complement currently used numerical definitions.
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http://dx.doi.org/10.1016/j.eururo.2020.12.040DOI Listing
January 2021

Implementation and Outcomes of Virtual Care Across a Tertiary Cancer Center During COVID-19.

JAMA Oncol 2021 Apr;7(4):597-602

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has burdened health care resources and disrupted care of patients with cancer. Virtual care (VC) represents a potential solution. However, few quantitative data support its rapid implementation and positive associations with service capacity and quality.

Objective: To examine the outcomes of a cancer center-wide virtual care program in response to the COVID-19 pandemic.

Design, Setting, And Participants: This cohort study applied a hospitalwide agile service design to map gaps and develop a customized digital solution to enable at-scale VC across a publicly funded comprehensive cancer center. Data were collected from a high-volume cancer center in Ontario, Canada, from March 23 to May 22, 2020.

Main Outcomes And Measures: Outcome measures were care delivery volumes, quality of care, patient and practitioner experiences, and cost savings to patients.

Results: The VC solution was developed and launched 12 days after the declaration of the COVID-19 pandemic. A total of 22 085 VC visits (mean, 514 visits per day) were conducted, comprising 68.4% (range, 18.8%-100%) of daily visits compared with 0.8% before launch (P < .001). Ambulatory clinic volumes recovered a month after deployment (3714-4091 patients per week), whereas chemotherapy and radiotherapy caseloads (1943-2461 patients per week) remained stable throughout. No changes in institutional or provincial quality-of-care indexes were observed. A total of 3791 surveys (3507 patients and 284 practitioners) were completed; 2207 patients (82%) and 92 practitioners (72%) indicated overall satisfaction with VC. The direct cost of this initiative was CAD$ 202 537, and displacement-related cost savings to patients totaled CAD$ 3 155 946.

Conclusions And Relevance: These findings suggest that implementation of VC at scale at a high-volume cancer center may be feasible. An agile service design approach was able to preserve outpatient caseloads and maintain care quality, while rendering high patient and practitioner satisfaction. These findings may help guide the transformation of telemedicine in the post COVID-19 era.
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http://dx.doi.org/10.1001/jamaoncol.2020.6982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791400PMC
April 2021

Sexual function and rehabilitation after radiation therapy for prostate cancer: a review.

Int J Impot Res 2021 Jan 6. Epub 2021 Jan 6.

Division of Urology, University Health Network (UHN), University of Toronto, Toronto, ON, Canada.

The treatment of prostate cancer is partly guided by patient preferences. Radical prostatectomy and radiation therapy are the standard radical therapies for localized disease and render comparable oncologic outcomes. Considering that survival is high regardless of the chosen treatment, factors such as treatment-related toxicities affecting the patients' quality of life play an important role in their decision. Notably, post-treatment sexual dysfunction, which includes decreased libido, erectile dysfunction, and ejaculatory dysfunction has been shown to be an important and prevalent concern of prostate cancer survivors. In this literature review, we sought to characterize the sexual complications associated with radiation therapy and map the available sexual rehabilitation options for prostate cancer survivors experiencing sexual dysfunction as a result of radiation therapy. We identified medical, non-biomedical, counseling, and lifestyle modification options for prostate cancer survivors seeking sexual rehabilitation. Future research in this area should address the standardization of sexual side-effect reporting and investigate sexual outcomes and rehabilitation in more diverse groups and of transgender and nonheterosexual prostate cancer survivors.
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http://dx.doi.org/10.1038/s41443-020-00389-1DOI Listing
January 2021

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer.

Eur Urol 2021 Mar 5;79(3):374-383. Epub 2020 Dec 5.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Context: Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.

Objective: To perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).

Evidence Acquisition: The review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446-52) and American Urology Association (AUA) criteria.

Evidence Synthesis: In total, 42 studies and 30407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n=12141), prospective registries (n=17053), and prospective and post hoc randomized trial analyses (n=1213). In 32 studies (n=12600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n=8543). GC use changed the management in active surveillance (number needed to test [NNT]=9) and postprostatectomy (NNT=1.5-4) settings in five studies (n=4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.

Conclusions: Consistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.

Patient Summary: In this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.
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http://dx.doi.org/10.1016/j.eururo.2020.11.021DOI Listing
March 2021

The reality of virtual care: Implications for cancer care beyond the pandemic.

Healthc (Amst) 2020 Dec 22;8(4):100480. Epub 2020 Oct 22.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, ON, Canada; Smart Cancer Care, Princess Margaret Cancer Centre, Toronto, ON, Canada; Techna Institute, University Health Network, Toronto, ON, Canada.

There has been longstanding interest in virtual care in oncology, but outdated reimbursement structures and a paradoxical lack of agility within electronic systems limited widespread adoption. Through the example of the Province of Ontario, Canada and the Princess Margaret Cancer Centre, we describe how a collective sense of action from COVID-19, a system of distributed leadership and decision-making, and the use of a Service Design process to map the ambulatory encounter onto a digital workflow were critical enablers of a large-scale virtual transition. Rigorous evaluation of virtual care models will be essential to maintain integration of virtual care post-pandemic.
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http://dx.doi.org/10.1016/j.hjdsi.2020.100480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578846PMC
December 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, University of Michigan School of Medicine, Ann Arbor.

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

Current topics in radiotherapy for genitourinary cancers: Consensus statements of the Genitourinary Radiation Oncologists of Canada.

Can Urol Assoc J 2020 Nov;14(11):E588-E593

Juravinski Cancer Centre, Hamilton Health Sciences, Hamilton, ON, Canada.

Introduction: The biennial meeting of the Genitourinary Radiation Oncologists of Canada (GUROC) took place November 22-23, 2019. A consensus-building session was held during the meeting addressing topics of emerging interest or controversy in the management of genitourinary malignancies.

Methods: Draft statements were debated among all meeting attendees in an open forum with anonymous live voting. Statements for which there was at least 75% agreement among attendees were adopted as GUROC consensus.

Results: Four evidence-based consensus statements were developed. First, the use of prostate radiotherapy is recommended in the setting of de novo low-volume metastatic hormone-sensitive prostate cancer to improve overall survival. Second, the support of ongoing randomized trials evaluating metastasis-directed ablative local therapy in oligometastatic prostate cancer is recommended; where such trials are available, off-trial use of oligometastasis-directed ablative radiotherapy at this time is strongly discouraged. Third, routine use of prostate-rectal hydrogel spacer devices in patients with localized prostate cancer planned to receive external beam radiotherapy is not recommended; instead, selective use in patients at highest risk of rectal toxicity may be considered. Finally, multidisciplinary consultation is recommended for all patients with newly diagnosed localized muscle-invasive bladder cancer.

Conclusions: The GUROC consensus statements provide practical guidance to clinicians in areas of current controversy in the management of prostate and bladder cancer, and it is hoped that their implementation will contribute to improved outcomes in real-world practice and greater support of clinical trials.
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http://dx.doi.org/10.5489/cuaj.6649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673835PMC
November 2020

Is there an association between a history of military service and cancer diagnosis? Results from a US national-level study of self-reported outcomes.

Cancer Causes Control 2021 Jan 16;32(1):47-55. Epub 2020 Oct 16.

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

Purpose: To examine cancer prevalence in men with and without military service history, using national-level self-reported outcomes.

Methods: A cross-sectional survey-based US study, including men aged 18 and above from the Health Information National Trends Survey database between 2011 and 2014. The primary endpoint was self-reported cancer prevalence. Multivariable logistic regression analyses assessed the association of various covariates with the prevalence of cancer.

Results: A total of 4,527 men were analyzed, with 1,352 (29.9%) reporting a history of military service. Compared to men with no military service history, men with a military service history were older (median of 65 [IQR 56, 74] vs. 53 [IQR 41, 62] years, p < 0.0001), more commonly Caucasian (71.4% vs. 61.4%, p < 0.0001), born in the US (95.6% vs. 79.5%, p < 0.0001), attained higher education level and annual household income (p < 0.0001), and consisted of more smokers(58.3% vs. 44.5%, p < 0.0001). The age-adjusted comparison demonstrated a higher cancer prevalence in men with military service history (20.5% vs. 7.6%, p < 0.0001). Specifically, genitourinary, dermatological, gastrointestinal, and hematological cancers were generally more prevalent. Adjusting for all available confounders, multivariable models showed that military service history was associated with 1.56 (95% CI 1.20-2.03), and 1.57 (95% CI 1.07-2.31) increased odds of having any cancer, and specifically genitourinary cancer, respectively.

Conclusions: Further research is needed to ascertain whether the association between military service and increased cancer diagnosis results from better screening programs or increased exposure to risk factors during military service.
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http://dx.doi.org/10.1007/s10552-020-01355-4DOI Listing
January 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

The suggested chemopreventive association of metformin with prostate cancer in diabetic patients.

Urol Oncol 2021 03 17;39(3):191.e17-191.e24. Epub 2020 Sep 17.

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

Purpose: Metformin, an insulin sensitizer, is the most common first-line antidiabetic therapy. There is increasing evidence suggesting metformin can prevent the emergence of prostate cancer (CaP). We aimed to analyze the chemopreventive role of metformin, in conjunction with other putative chemopreventive medications (statins, proton-pump-inhibitors, alpha-blockers, 5-alpha-reductase inhibitors, diabetic medications) in a population-based cohort study.

Methods: Data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all diabetic men aged 66 and above with prior history of a negative prostate biopsy (PB) between 1994 and 2016, who were not on any of the medications prior to study inclusion. Multivariable Cox regression models with time-dependent covariates were used to assess the association of metformin to CaP diagnosis, subsequent PB, and use of androgen deprivation therapy (ADT). All models were adjusted for age, rurality, comorbidity, and year of study inclusion.

Results: Overall, 2,332 diabetic men were included, with a median follow-up time of 9.4 years (interquartile range 5.4-13.4 years). A total of 2,036 patients (87.3%) received metformin. Compared to non-metformin users, metformin use was associated with decreased CaP diagnosis rate (HR 0.69, 95%CI 0.54-0.88, P = 0.003), lower hazard of undergoing an additional PB (HR 0.64, 95%CI 0.44-0.95, P = 0.03), and receiving ADT (HR 0.72, 95%CI 0.54-0.96, P = 0.003).

Conclusion: Men receiving metformin were less likely to have suspected or diagnosed CaP, and in those with CaP, the use of ADT was less common. Ongoing prospective randomized studies will determine if these findings correspond to the suggested associations of metformin in the emergence and/or progression of CaP.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.032DOI Listing
March 2021

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

BJU Int 2020 Sep 14. Epub 2020 Sep 14.

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

Objectives: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease.

Patients And Methods: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC.

Results: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort.

Conclusions: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.
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http://dx.doi.org/10.1111/bju.15236DOI Listing
September 2020

Virtual care models for cancer survivorship.

NPJ Digit Med 2020 2;3:113. Epub 2020 Sep 2.

Division of Urology, Department of Surgery, University of Toronto, Toronto, ON Canada.

Virtual care models for cancer survivorship are needed to support patients living with the chronic effects of cancer treatment, while increasing health system capacity. Characteristics that may be critical to their success have not been adequately studied. This scoping review summarizes previous efforts to virtualize survivorship care to inform future innovations in the field. Four databases were searched for articles published before January 2020, and 24 articles that met selection criteria were included in this analysis. Rationale for pursuing virtual models of care shared two common objectives: (1) the need for sustainable survivorship care, and (2) the opportunity to improve survivorship outcomes. Breast cancer ( = 10) and prostate cancer ( = 4) were the most targeted cancers for virtual survivorship care. The implemented technologies included web platforms ( = 15), telephone calls ( = 12), and smartphone or tablet applications ( = 5). A variety of healthcare professionals were effectively involved in the provision of virtual care. Future virtual care models may benefit from integrating with existing health systems and services, repurposing common technologies, involving allied health professionals, and engaging patients and caregivers from diverse communities in the design of virtual services.
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http://dx.doi.org/10.1038/s41746-020-00321-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468136PMC
September 2020

The deleterious association between proton pump inhibitors and prostate cancer-specific mortality - a population-based cohort study.

Prostate Cancer Prostatic Dis 2020 12 8;23(4):622-629. Epub 2020 Jul 8.

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

Background: Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort.

Methods: We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year.

Results: Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis.

Conclusions: Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.
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http://dx.doi.org/10.1038/s41391-020-0248-9DOI Listing
December 2020

The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer.

Eur Urol Focus 2020 Jun 30. Epub 2020 Jun 30.

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Background: The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins.

Objective: To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy.

Design, Setting, And Participants: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr).

Outcome Measurements And Statistical Analysis: Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models.

Results And Limitations: Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies.

Conclusions: Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration.

Patient Summary: Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.
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http://dx.doi.org/10.1016/j.euf.2020.06.005DOI Listing
June 2020

Determining the Impact of Spatial Heterogeneity on Genomic Prognostic Biomarkers for Localized Prostate Cancer.

Eur Urol Oncol 2020 Jun 27. Epub 2020 Jun 27.

Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Techna Institute, University Health Network, Toronto, ON, Canada. Electronic address:

Localized prostate tumors show remarkably diverse clinical courses, with some being cured by local therapy alone, while others rapidly relapse and have a lethal course despite precision surgery or radiotherapy. Many genomic biomarkers have been developed to predict this clinical behavior, but these are confounded by the extreme spatial heterogeneity of prostate tumors: most are multifocal and harbor multiple subclonal populations. To quantify the influence of spatial heterogeneity on genomic prognostic biomarkers, we developed a case-control high-risk cohort (n = 42) using a prospective registry, risk matched by clinicopathologic prognostic indices. Half of the cohort had early biochemical recurrence (BCR; ie, ≤18 mo), while half remained without evidence of disease for at least 48 mo after radical prostatectomy. We then genomically profiled multiple tumor foci per patient, analyzing 119 total specimens. These data allowed us to validate three published genomic prognostic biomarkers and quantify their sensitivity to tumor spatial heterogeneity. Remarkably, all three biomarkers robustly predicted early BCR, and all three were robust to spatiogenomic variability. These data suggest that DNA-based genomic biomarkers can overcome intratumoral heterogeneity: single biopsies may be sufficient to estimate the risk of early BCR after radical treatment in patients with high-risk disease. PATIENT SUMMARY: We investigated whether heterogeneity between tumor regions within the prostate affects the accuracy of DNA-based biomarkers predicting early relapse after prostatectomy. We observed persistent accuracy in predicting disease relapse, suggesting that spatial heterogeneity may not hinder biomarker performance.
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http://dx.doi.org/10.1016/j.euo.2020.06.005DOI Listing
June 2020

Canadian experience of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy for muscle-invasive bladder cancer.

Can Urol Assoc J 2020 Dec;14(12):404-410

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

Introduction: Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Neoadjuvant chemotherapy (NAC) was proven to cause pathological downstaging. For this reason, we evaluated whether receipt of NAC decreases local bladder recurrences in TMT patients.

Methods: We retrospectively analyzed our TMT database for all patients treated between 2003 and 2017. Patients were treated with maximal transurethral resection of bladder tumor (TURBT) followed by chemotherapy/radiotherapy with or without NAC. Baseline demographic and tumor characteristics were recorded. Rates of local and systemic recurrence were analyzed per receipt of NAC. Overall recurrence-free survival (RFS) and bladder (b)RFS were analyzed using the Kaplan-Meier method and Cox proportional hazards modelling.

Results: Median age and followup periods were 72 years and 3.6 years, respectively. Fifty-four patients had NAC and concurrent chemoradiation (NAC-TMT) vs. 70 patients who had concurrent chemoradiation only (TMT). Carcinoma in situ (CIS) was present in 31% of the patients in NAC-TMT group compared to 24% in TMT group (p=0.40). After treatment, 24 (44%) and 31 (44%) patients in NAC-TMT and TMT groups, respectively, had bladder tumor recurrence. Overall RFS at three years was 46% and 50% in NAC-TMT and TMT groups, respectively (p=0.70). BRFS at three years was 55% and 69% in NAC-TMT and TMT groups, respectively (p=0.27). Multivariable analyses found that the presence of concomitant CIS (hazard ratio [HR] 2.13; 95% confidence interval CI 1.06-4.27; p=0.0036) was the primary factor associated with local bladder recurrence.

Conclusions: Receipt of NAC does not obviate the risk of bladder recurrence post-TMT. Patients with CIS should be monitored especially closely for local recurrence.
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http://dx.doi.org/10.5489/cuaj.6459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704086PMC
December 2020

Transitioning to a New Normal in the Post-COVID Era.

Curr Oncol Rep 2020 06 22;22(7):73. Epub 2020 Jun 22.

Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 6M9, Canada.

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http://dx.doi.org/10.1007/s11912-020-00956-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306409PMC
June 2020

Use of combined androgen deprivation therapy with postoperative radiation treatment for prostate cancer: Impact of randomized trials on clinical practice.

Urol Oncol 2020 11 16;38(11):848.e1-848.e7. Epub 2020 Jun 16.

Department of Radiation Oncology, University of Toronto, Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Canada; Techna Institute, University Health Network, Canada. Electronic address:

Purpose: To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP).

Material And Methods: Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1 = P1), July 2011 to December 2012 (Period 2 = P2), and January 2017 to June 2018 (Period 3 = P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value <0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015.

Results: Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered >1 year post-RP with undetectable PSA or PSA >0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P < 0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (P = 0.04). International Society of Urological Pathology grade ≥4 (P < 0.002) and pre-PORT PSA >0.5 ng/ml (P < 0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P < 0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015.

Conclusion: The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy.
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http://dx.doi.org/10.1016/j.urolonc.2020.04.019DOI Listing
November 2020

Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases.

Adv Radiat Oncol 2020 May-Jun;5(3):350-357. Epub 2019 Nov 26.

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Purpose: Brain metastases (BrM) are common in patients with epidermal growth factor receptor (EGFRm) mutant non-small cell lung cancer (NSCLC). We sought to determine the rate of neurologic death (ND) in this population.

Methods And Materials: We analyzed data from 198 patients who received a diagnosis of BrM from EGFRm NSCLC between 2004 and 2016, comparing patients whose initial treatment for BrM was stereotactic radiosurgery with or without tyrosine kinase inhibitors (TKI), whole brain radiation therapy (WBRT) with or without TKI, or TKI alone. The incidence of ND was determined using a competing risks analysis. Univariate and multivariate analyses were used to identify clinical variables associated with this outcome.

Results: The percentage of patients who initially received stereotactic radiosurgery, whole brain radiation therapy, or TKI alone was 22%, 61%, and 17%, respectively. Median overall survival in these subgroups was 31.1, 14.6, and 24.6 months, respectively ( = .0016). The 5-year incidence of ND among all patients was 40% and did not significantly vary according to treatment group. In a multivariable model, only leptomeningeal disease at any point in a patient's disease course significantly correlated with ND (hazard ratio 4.75, <.001).

Conclusions: Among our cohort of patients with BrM from EGFRm NSCLC, the incidence of ND was significantly higher than suggested by previous reports. BrM should be considered a driver of mortality in many patients with EGFRm NSCLC, and treatments providing better control of BrM, lower neurocognitive side effects, and maintenance of quality of life are needed.
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http://dx.doi.org/10.1016/j.adro.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276684PMC
November 2019

Predictors of prostate-specific antigen testing in men aged ≥55 years: A cross-sectional study based on patient-reported outcomes.

Int J Urol 2020 Sep 31;27(9):711-718. Epub 2020 May 31.

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

Objectives: To examine the predictors of prostate-specific antigen discussion with a physician and prostate-specific antigen testing in men aged ≥55 years.

Methods: Utilizing the USA Health Information National Trends Survey, 4th Ed., a cross-sectional study from 2011 to 2014 was carried out to analyze the factors predicting prostate-specific antigen testing and discussion in men ≥55 years. Associations between each covariate and prostate-specific antigen discussion/testing were determined. Multivariable logistic regression models were used to determine clinically relevant predictors of prostate-specific antigen discussion/testing. Due to multiple comparisons, the Bonferroni correction was used.

Results: A total of 2731 men included in the Health Information National Trends Survey were analyzed. Several socioeconomic parameters were found to increase the likelihood of men aged ≥55 years to undergo prostate-specific antigen testing: living with a spouse, a higher level of education (college graduate or above), a higher income (>$50 000 annually) and previous history of any cancer. In contrast, current smokers were less likely to undergo prostate-specific antigen testing. Having a prostate-specific antigen discussion with a physician was more likely for men surveyed in 2014, for men who were living with a spouse, who had a higher annual income (>$50 000 annually) and those with a history of any cancer.

Conclusions: Significant inequalities in prostate-specific antigen testing and discussion exist among men in the USA, mainly driven by socioeconomic factors. Ideally, prostate-specific antigen testing and discussion should be based on relevant clinical factors with a shared decision-making approach for every man. Therefore, a better understanding of the socioeconomic factors influencing prostate-specific antigen testing/discussions can inform strategies to reduce existing gaps in care.
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http://dx.doi.org/10.1111/iju.14276DOI Listing
September 2020

Tumor-targeted dose escalation for localized prostate cancer using MR-guided HDR brachytherapy (HDR) or integrated VMAT (IB-VMAT) boost: Dosimetry, toxicity and health related quality of life.

Radiother Oncol 2020 08 22;149:240-245. Epub 2020 May 22.

Princess Margaret Cancer Center, University Health Network, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada.

Purpose: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer.

Materials And Methods: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/β 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC).

Results: Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p < 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p > 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p < 0.05) and recovered baseline scores at 6 months.

Conclusion: Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control.
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http://dx.doi.org/10.1016/j.radonc.2020.05.029DOI Listing
August 2020

Psychological distress associated with active surveillance in patients younger than 70 with a small renal mass.

Urol Oncol 2020 06 3;38(6):603.e17-603.e25. Epub 2020 Apr 3.

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

Purpose: To compare the psychological distress throughout several predefined disease time points in patients younger than 70 with small renal masses (SRMs) treated with either active surveillance (AS) or ablative/surgical therapy.

Methods: Using the Edmonton Symptom Assessment System - revised (ESAS-r) questionnaire, we focused on psychological distress symptoms in all consecutive patients with an SRM between 2014 and 2017. We further evaluated the psychological distress sub-score (PDSS) of ESAS-r, consisting of the sum scores of anxiety, depression, and well-being. PDSS of patients treated with AS or ablation/surgery were compared at 4 distinct time points (before and after diagnosis, after a biopsy is performed, and at last follow-up). Multivariable linear regression models were performed to assess factors associated with worse PDSS (1-point score increase).

Results: We examined 477 patients, of whom 217 and 260 were treated with AS and surgery/ablation, respectively. Similar ESAS-r and PDSS scores were shown at all predefined disease time points except following an SRM biopsy and at last, follow-up, where AS-treated patients with a biopsy-proven malignancy had significantly worse PDSS (11.4 vs. 6.1, P = 0.035), and (13.2 vs. 5.4, P = 0.004), respectively. At last follow-up, multivariable linear models demonstrated that a biopsy-proven malignancy (B = 2.630, 95% CI 0.024-5.236, P = 0.048) and AS strategy (B = 6.499, 95% CI 2.340-10.658, P = 0.002) were associated with worse PDSS in all patients, and in those who underwent a biopsy, respectively.

Conclusions: Offering standardized psychological supportive care may be required for patients younger than 70 years on AS for SRM, especially for those with a biopsy-proven tumor.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.015DOI Listing
June 2020

Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier.

Prostate Cancer Prostatic Dis 2020 12 30;23(4):646-653. Epub 2020 Mar 30.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

Background: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.

Methods: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score.

Results: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71.

Conclusions: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.
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http://dx.doi.org/10.1038/s41391-020-0226-2DOI Listing
December 2020

F-DCFPyL PET/CT in Patients with Subclinical Recurrence of Prostate Cancer: Effect of Lesion Size, Smoothing Filter, and Partial-Volume Correction on PROMISE Criteria.

J Nucl Med 2020 11 20;61(11):1615-1620. Epub 2020 Mar 20.

Joint Department of Medical Imaging, Princess Margaret Hospital, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, Toronto, Ontario, Canada

Our purpose was to determine the effect of a smoothing filter and partial-volume correction (PVC) on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on molecular imaging PSMA (miPSMA) scoring. Men who had biochemical recurrence of prostate cancer with negative findings on CT and bone scintigraphy were referred for F-DCFPyL (2-(3-(1-carboxy-5-[(6-F-fluoro-pyridine-3-carbonyl)-amino]-pentyl) PET/CT. Examinations were performed on 1 of 2 different brands of PET/CT scanner. All suspected tumor sites were manually contoured on coregistered CT and PET images, and each was assigned an miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomic CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified rule-of-thumb (RoT) correction factor (CF) was derived for lesions at various sizes (<4 mm, 4-7 mm, 7-9 mm, and 9-12 mm). This CF was then applied to the original dataset and the miPSMA scores that were obtained using the RoT CF were compared with those obtained using the actual corrections. There were 75 men (median age, 69 y; median serum PSA, 3.69 μg/L) with 232 metastatic nodes less than 12 mm in diameter (mean lesion volume, 313.5 ± 309.6 mm). The mean SUV before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively ( < 0.00001). The mean CF for lesions smaller than 4 mm ( = 22), 4-7 mm ( = 140), 7-9 mm ( = 50), and 9-12 mm ( = 20) was 4 (range, 2.5-6.4), 2.8 (range, 1.6-4.9), 2.3 (range, 1.6-3.3), and 1.8 (range, 1.4-2.4), respectively. Overall, the miPSMA scores were concordant between the corrected dataset and the RoT dataset for 205 of 232 lesions (88.4%). A smoothing filter and PVC had a significant effect on measured PSMA activity in small nodal metastases, impacting the miPSMA score.
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http://dx.doi.org/10.2967/jnumed.120.241737DOI Listing
November 2020