Publications by authors named "Armen Aprikian"

188 Publications

Stereotactic Ablative Radiotherapy for the Treatment of Upper Urinary Tract Urothelial Carcinoma.

Pract Radiat Oncol 2021 Sep 13. Epub 2021 Sep 13.

McGill University Health Centre, Department of Radiation Oncology, Montreal, QC, Canada. Electronic address:

Purpose: Urothelial carcinomas (UC), also known as transitional cell carcinomas, account for the majority of upper urinary tract tumors. The gold-standard therapy for operable patients with localized disease is radical nephroureterectomy. However, some patients are not surgical candidates. Data on the use of modern radiotherapy (RT) for upper urinary tract UC (UTUC) is scarce. The purpose of this study was to assess the safety and efficacy of stereotactic ablative radiotherapy (SABR) in UTUC.

Materials And Methods: This retrospective study included all patients with UTUC treated with SABR at one institution. Charts were reviewed to evaluate renal function and development of toxicity using CTCAE v3.0. Tumor response on follow-up imaging with CT- or MRI-scans was assessed using the RECIST 1.1 criteria.

Results: A total of 16 patients, 7 patients with UC at the ureter and 9 at the renal pelvis, were identified as being treated with SABR. Of the 9 patients with renal pelvis UC, 4 had a previous history of bladder cancer. At the time of treatment median age was 85 years (67-95 years). Most patients received 40 Gy in 8 fractions every second day. The median follow-up was 21 months (3-110 months). Most patients maintained a stable renal function, with only 2 patients developing worsening chronic kidney disease, but none requiring dialysis. Acutely, 4 patients developed grade 1 diarrhea, and 1 patient had new grade 1 hematuria. No chronic side effects were observed. One patient did not have follow-up imaging and was thus excluded from tumor response analysis. Two patients had complete response of the treated lesion, 9 had partial response, 2 had stable disease, and 2 had disease progression within the treatment field.

Conclusions: This small case series suggests that SABR for UTUC is safe and well-tolerated, with good radiographic tumor response to ablative doses of RT.
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http://dx.doi.org/10.1016/j.prro.2021.07.006DOI Listing
September 2021

Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression.

Br J Cancer 2021 Jul 7;125(1):78-84. Epub 2021 Apr 7.

Centre Hospitalier Universitaire (CHU) de Québec Research Center and Faculty of Medicine, Laval University, Québec, Canada.

Background: Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes.

Methods: Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS).

Results: The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-methoxyestrone were associated with an increased risk of development of metastasis/deaths.

Conclusions: Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.
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http://dx.doi.org/10.1038/s41416-021-01376-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257651PMC
July 2021

The Use of 5-Alpha Reductase Inhibitors and Alpha-1 Blockers Does Not Improve Clinical Outcome in Male Patients Undergoing Radical Cystectomy for Bladder Cancer in Quebec, Canada.

Clin Genitourin Cancer 2021 08 6;19(4):371-371.e9. Epub 2021 Feb 6.

Department of Surgery, McGill University Health Centre, Montreal, QC, Canada; Department of Oncology, McGill University, Montreal, QC, Canada.

Background: Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5α-reductase inhibitors and/or α-blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5α-reductase inhibitors or α-blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC).

Patients And Methods: Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion.

Results: Of the 2822 patients included, 284 patients used 5α-reductase inhibitors and 1001 patients used α-blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5α-reductase inhibitors or α-blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5α-reductase inhibitors prior to surgery and controls who never used 5α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33).

Conclusion: Preoperative use of 5α-reductase inhibitors and α-blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer.
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http://dx.doi.org/10.1016/j.clgc.2021.01.007DOI Listing
August 2021

Phase 1 Trial of Atezolizumab Plus Trimodal Therapy in Patients With Localized Muscle-Invasive Bladder Cancer.

Int J Radiat Oncol Biol Phys 2021 07 6;110(3):738-741. Epub 2021 Jan 6.

Division of Urology, University Health Centre, McGill University, Montreal, Canada. Electronic address:

Purpose: Immune checkpoint programmed death-ligand 1 inhibitor therapy has shown response in metastatic muscle invasive bladder cancer (MIBC). We evaluated the safety and tolerability of atezolizumab (anti-programmed death-ligand 1) in combination with trimodal therapy in patients with localized MIBC.

Methods And Materials: A prospective nonrandomized phase 1 study using a 3 + 3 design was conducted in patients with localized MIBC (T2-T4a N0M0) treated on a bladder preservation program. After transurethral resection of bladder tumor, patients received concurrent radiation therapy at a fixed dose of 50 Gy in 20 fractions, gemcitabine (100 mg/m, intravenously once weekly for 4 weeks) and atezolizumab (1200 mg intravenously every 3 weeks for 16 cycles). The primary endpoint was safety/toxicity profile.

Results: Between May 2018 and March 2019, 8 patients (6 male and 2 female) were enrolled. The first 5 patients received atezolizumab at 1200 mg, 3 of whom developed grade 3 side effects (2 of them dose-limiting toxicity). Atezolizumab dose was reduced to 840 mg for 3 additional patients. The study was terminated due to the presence of 3 grade 3 adverse events (2 of which were dose-limiting toxicity) despite the reduced atezolizumab dose. Gastrointestinal events were the main toxicity. No grade 4 to 5 adverse effects were observed.

Conclusions: Concurrent administration of atezolizumab with concomitant hypofractionated radiation therapy and gemcitabine appears to be associated with unacceptable gastrointestinal toxicity. Although the numbers studied are small, our results suggest considerable caution with its concurrent use with trimodal therapy for MIBC.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.033DOI Listing
July 2021

Refining assessment of response to radiation-based therapy for muscle-invasive bladder cancer: Is post-treatment tumor bed biopsy always necessary?

Urol Oncol 2021 05 23;39(5):299.e7-299.e14. Epub 2020 Oct 23.

Department of Urology, McGill University Health Centre, McGill University, Montreal, QC, Canada. Electronic address:

Introduction: Radiation-based therapy (RT) has emerged as a suitable alternative to radical cystectomy (RC) and pelvic lymph node dissection for muscle-invasive bladder cancer (MIBC) patients. Routine biopsy after RT to rule out residual disease remains inconsistent across guidelines. Our objective was to review the significance of a bladder biopsy in terms of assessment of response post-RT and its potential impact on survival.

Patients And Methods: This was a single-center retrospective study on patients with MIBC (cT2-4aN0-2M0) treated with curative intent RT. A total of 169 patients with primary urothelial carcinoma were analyzed. Patients' demographic, clinical and pathological variables, imaging, cystoscopy, urine cytology, and biopsy reports after RT were collected and compiled. Whenever urine cytology was positive or cystoscopy showed any malignant-appearing lesion, the first assessment post-RT was considered suspicious for residual disease. A descriptive population analysis was reported. Cox regression multivariable analysis was performed to identify independent variables associated with survival outcomes.

Results: Median age was 75 years (interquartile range 66-82) and clinical staging was cT2 in 152 (90%) patients. Cytology and cystoscopy were normal in 140 (83%) after RT. Of patients with a control biopsy, residual MIBC was present in 3 (5%) and non-MIBC in another 6 (11%). On the contrary, a for-cause biopsy due to a suspicious assessment post-RT did not yield residual cancer in 45% of patients. Multivariable analysis showed that age (hazard ratio [HR] 1.04, P< 0.001), lymphovascular invasion (HR 1.68, P = 0.03) and a suspicious assessment after RT (HR 3.21; P< 0.001) were significantly associated with worse OS. This study was limited by its retrospective design.

Conclusions: A routine biopsy after RT may be warranted to assess treatment response. This might be particularly important for patients who may benefit from early surgical intervention for residual MIBC. Further prospective studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.001DOI Listing
May 2021

When will I have my surgery?

Authors:
Armen G Aprikian

Can Urol Assoc J 2020 Dec;14(12):371

CUA Vice-President.

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http://dx.doi.org/10.5489/cuaj.7031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704089PMC
December 2020

Contemporary Population-Based Analysis of Bone Mineral Density Testing in Men Initiating Androgen Deprivation Therapy for Prostate Cancer.

J Natl Compr Canc Netw 2020 10 1;18(10):1374-1381. Epub 2020 Oct 1.

Division of Urology, Department of Surgery, McGill University.

Background: Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer (PCa); however, it accelerates the loss of bone mineral density (BMD), which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to assess baseline fracture risk properly. The objective of this study was to examine the proportion of BMD testing in men initiating ADT in Quebec and to identify factors associated with receipt of this testing.

Methods: The study cohort consisted of men extracted from Quebec public healthcare insurance administrative databases who initiated continuous ADT from 2000 to 2015 for >12 months. The primary study outcome was receipt of BMD testing in the period from 6 months before through 12 months after ADT initiation. Multivariable generalized linear mixed regression modeling with a logit link was performed to identify variables associated with BMD testing.

Results: We identified 22,033 patients, of whom 3,910 (17.8%) underwent BMD testing. Rates of BMD testing increased from 4.1% in 2000 to 23.4% in 2015. After multivariable analyses, prior history of osteoporosis (odds ratio [OR], 1.84; 95% CI, 1.32-2.57; P<.001), rheumatoid arthritis (OR, 1.64; 95% CI, 1.15-2.34; P=.006), use of bisphosphonates (OR, 1.47; 95% CI, 1.25-1.73; P<.001), and long-term corticosteroid use (OR, 1.63; 95% CI, 1.15-2.31; P=.006) were associated with higher odds of BMD testing. Patient age >80 years (OR, 0.67; 95% CI, 0.59-0.76; P<.001), metastases (OR, 0.79; 95% CI, 0.70-0.89; P<.001), higher Charlson comorbidity score (OR, 0.65; 95% CI, 0.51-0.81; P<.001), and rural residence (OR, 0.77; 95% CI, 0.68-0.87; P<.001) were associated with lower odds of BMD testing.

Conclusions: In our study population, BMD testing rates in men initiating ADT were low, although they increased over the years especially in the years after the publication of recommendations for BMD testing in these patients. Potential gaps identified include being older, more comorbid, and rural areas. Overall, additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.
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http://dx.doi.org/10.6004/jnccn.2020.7576DOI Listing
October 2020

Design and Development of a Fully Synthetic Multiplex Ligation-Dependent Probe Amplification-Based Probe Mix for Detection of Copy Number Alterations in Prostate Cancer Formalin-Fixed, Paraffin-Embedded Tissue Samples.

J Mol Diagn 2020 10 4;22(10):1246-1263. Epub 2020 Aug 4.

Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

DNA copy number alterations (CNAs) are promising biomarkers to predict prostate cancer (PCa) outcome. However, fluorescence in situ hybridization (FISH) cannot assess complex CNA signatures because of low multiplexing capabilities. Multiplex ligation-dependent probe amplification (MLPA) can detect multiple CNAs in a single PCR assay, but PCa-specific probe mixes available commercially are lacking. Synthetic MLPA probes were designed to target 10 CNAs relevant to PCa: 5q15-21.1 (CHD1), 6q15 (MAP3K7), 8p21.2 (NKX3-1), 8q24.21 (MYC), 10q23.31 (PTEN), 12p13.1 (CDKN1B), 13q14.2 (RB1), 16p13.3 (PDPK1), 16q23.1 (GABARAPL2), and 17p13.1 (TP53), with 9 control probes. In cell lines, CNAs were detected when the cancer genome was as low as 30%. Compared with FISH in radical prostatectomy formalin-fixed, paraffin-embedded samples (n = 18: 15 cancers and 3 matched benign), the MLPA assay showed median sensitivity and specificity of 80% and 93%, respectively, across all CNAs assessed. In the validation set (n = 40: 20 tumors sampled in two areas), the respective sensitivity and specificity of MLPA compared advantageously with FISH and TaqMan droplet digital PCR (ddPCR) when assessing PTEN deletion (FISH: 85% and 100%; ddPCR: 100% and 83%) and PDPK1 gain (FISH: 100% and 92%; ddPCR: 93% and 100%). This new PCa probe mix accurately identifies CNAs by MLPA across multiple genes using low quality and quantities (50 ng) of DNA extracted from clinical formalin-fixed, paraffin-embedded samples.
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http://dx.doi.org/10.1016/j.jmoldx.2020.07.003DOI Listing
October 2020

Are basic robotic surgical skills transferable from the simulator to the operating room? A randomized, prospective, educational study.

Can Urol Assoc J 2020 Dec;14(12):416-422

Division of Urology, McGill University Health Centre, Montreal, QC, Canada.

Introduction: We aimed to assess the transferability of basic robotic skills from the simulator to the operating room (OR) while performing robotic-assisted radical prostatectomy (RARP).

Methods: Fourteen urology residents were randomized into two groups: group A was required to practice three sessions (nine tasks each) on the simulator, whereas group B was required to practice (same nine tasks) until they reached competency. Both groups were recorded while practicing on the da Vinci Surgical Skills Simulator. Both groups were then recorded while performing bladder mobilization during RARP. Senior residents from both groups were also recorded while performing urethro-vesical anastomosis during RARP. Recordings were assessed blindly using the validated Global Evaluative Assessment of Robotic Skills (GEARS) tool by C-SATS. Spearman's correlation coefficient (rho) was used to assess correlation between GEARS scores from practice sessions on the da Vinci Simulator and the GEARS scores from bladder mobilization and urethro-vesical anastomosis during RARP.

Results: There was no difference in total GEARS scores between the two groups in the OR. Total GEARS scores for "ring and rail 2" and "suture sponge" tasks correlated with the total GEARS scores during urethro-vesical anastomosis (rho=0.86, p=0.007; rho=0.90, p=0.002, respectively). GEARS' efficiency component during "energy and dissection" task on the da Vinci Simulator correlated with GEARS' efficiency component during bladder mobilization (rho=0.62, p=0.03). GEARS' force sensitivity component during "ring and rail 2" and "dots and needles" tasks on the da Vinci Simulator correlated with GEARS' force sensitivity component during bladder mobilization (rho=0.58, p=0.047; rho =0.65, p=0.02, respectively).

Conclusions: Objective assessments of urology residents on the da Vinci Surgical Skills Simulator tasks ring and rail 2 and suture sponge correlated with their objective assessments of bladder mobilization and urethro-vesical anastomosis. Therefore, basic robotic skills could be transferred from the simulator to the OR.
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http://dx.doi.org/10.5489/cuaj.6460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704095PMC
December 2020

Guidance for management of cancer surgery during the COVID-19 pandemic.

Can J Surg 2020 05;63(22):S2-S4

From the Canadian Partnership Against Cancer (Finley, Prashad, Camuso, Daly, Earle); the Canadian Network of Surgical Associations for Cancer Care (Aprikian, Ball, Bentley, Charest, Fata, Helyer, O'Connell, Moloo, Seely, Werier, Zhong); the Canadian Urological Association and the Division of Urology, Department of Surgery, McGill University, Montreal, Que. (Aprikian); the Canadian Hepato-Pancreatico-Biliary Association and the Department of Surgery, University of Calgary, Calgary, Alta. (Ball); the Society for Gynecologic Oncology of Canada and the Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, NS (Bentley); the Canadian Neurosurgical Society and the Department of Neurosurgery, Dalhousie University New Brunswick, Moncton, NB (Charest); the Canadian Association of General Surgeons and the Division of General Surgery, Department of Surgery, McGill University, Montreal, Que. (Fata); the Canadian Society of Surgical Oncology and the Department of General Surgery, Dalhousie University, Halifax, NS (Helyer); the Canadian Association of Head and Neck Surgical Oncology and the Division of Otolaryngology - Head and Neck Surgery, University of Alberta, Edmonton, Alta.(O'Connell); the Canadian Society of Colon and Rectal Surgeons and the Division of General Surgery, Department of Surgery, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Ont. (Moloo); the Canadian Association of Thoracic Surgeons and the Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ont. (Seely); the Canadian Orthopaedic Oncology Society and the Division of Orthopaedic Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Werier); the Canadian Society of Plastic Surgeons and the Department of Surgery, University of Toronto, Toronto, Ont. (Zhong); the Department of Surgery, McMaster University, Hamilton, Ont. (Finley); the Department of Gastrointestinal Oncology, Sunnybrook Health Sciences Centre, Toronto, Ont. (Earle); and the Canadian Journal of Surgery (Ball).

Summary: During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.
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http://dx.doi.org/10.1503/cjs.005620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828991PMC
May 2020

The use of perioperative chemotherapy in patients undergoing radical cystectomy for bladder cancer in Quebec, Canada, 2000-2016.

Can Urol Assoc J 2020 May 29;14(5):E191-E201. Epub 2019 Nov 29.

Department of Surgery, McGill University Health Centre, Montreal, QC, Canada.

Introduction: Despite its proven benefit, studies have reported poor use of perioperative chemotherapy (POC) in bladder cancer patients undergoing radical cystectomy (RC). We evaluated POC use in Quebec between January 2000 and September 2016.

Methods: Using provincial health administrative databases, data were retrospectively collected from patients from two years before RC until December 2016 or death. Logistic regression was used to identify variables predicting POC use. Survival analyses were conducted using Cox regression. Analyzed covariates were age, sex, comorbidities, year of RC, residence and hospital region, distance to hospital, hospital type and size, and hospital's and surgeon's RC volume.

Results: A total of 790/4656 patients (17.0%) received POC. Neoadjuvant chemotherapy (NAC) use increased in recent years: 3.5% (2009), 11.2% (2012), and 20.7% (2015). POC use was increased in patients with recent surgery, a younger age, less comorbidities, residing closer to the hospital of surgery, and a high surgeon's RC volume (p<0.05). For patients treated between 2013 and 2016, a younger age (odds ratio [OR] 0.71; 95% confidence interval [CI] 0.64-0.80 per five years), shorter distance to the hospital (OR 0.88; 95% CI 0.77-0.99 per 50 km), surgery in an academic hospital (OR 1.86; 95% CI 1.06-3.29), and recent surgery (OR 1.34; 95% CI 1.14-1.58 per year) independently predicted NAC use. These NAC users had a significantly higher overall survival rate than patients without POC (hazard ratio 0.73; 95% CI 0.55-0.97). Limitations include missing data on pathological staging.

Conclusions: NAC/POC use increased in Quebec but was lower compared to most developed countries. Its use was lower in patients residing further from the hospital and in those treated in non-academic hospitals.
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http://dx.doi.org/10.5489/cuaj.6094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197966PMC
May 2020

Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Eur Urol 2019 12 16;76(6):831-842. Epub 2019 Sep 16.

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.

Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.

Design, Setting, And Participants: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.

Outcome Measurements And Statistical Analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.

Results And Limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p =  0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p =  0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p =  0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).

Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.

Patient Summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.
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http://dx.doi.org/10.1016/j.eururo.2019.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880781PMC
December 2019

Improving ultrasound-based prostate volume estimation.

BMC Urol 2019 Jul 24;19(1):68. Epub 2019 Jul 24.

Urologic Oncology Research Group, Cancer Research Program, Research Institute (RI) of McGill University Health Center (MUHC), Glen Campus, E M2.2210, 1001 Blvd Décarie, Montréal, Qc, H4A 3J1, Canada.

Background: To define a new coefficient to be used in the formula (Volume = L x H x W x Coefficient) that better estimates prostate volume using dimensions of fresh prostates from patients who had transrectal ultrasound (TRUS) imaging prior to prostatectomy.

Methods: The prostate was obtained from 153 patients, weighed and measured to obtain length (L), height (H), and width (W). The density was determined by water displacement to calculate volume. TRUS data were retrieved from patient charts. Linear regression analyses were performed to compare various prostate volume formulas, including the commonly used ellipsoid formula and newly introduced bullet-shaped formula.

Results: By relating measured prostate volumes from fresh prostates to TRUS-estimated prostate volumes, 0.66 was the best fitting coefficient in the (L x H x W x Coefficient) equation. This newfound coefficient combined with outlier removal yielded a linear equation with an R of 0.64, compared to 0.55 and 0.60, for the ellipsoid and bullet, respectively. By comparing each of the measured vs. estimated dimensions, we observed that the mean prostate height and length were overestimated by 11.1 and 10.8% using ultrasound (p < 0.05), respectively, while the mean width was similar (p > 0.05). Overall, the ellipsoid formula underestimates prostate volumes by 18%, compared to an overestimation of 4.6 and 5.7% for the bullet formula and the formula using our coefficient, respectively.

Conclusions: This study defines, for the first time, a coefficient based on freshly resected prostates as a reference to estimate volumes by imaging. Our findings support a bullet rather than an ellipsoid prostate shape. Moreover, substituting the coefficient commonly used in the ellipsoid formula by our calculated coefficient in the equation estimating prostate volume by TRUS, provides a more accurate value of the true prostate volume.
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http://dx.doi.org/10.1186/s12894-019-0492-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657110PMC
July 2019

Validation of the prognostic value of NF-κB p65 in prostate cancer: A retrospective study using a large multi-institutional cohort of the Canadian Prostate Cancer Biomarker Network.

PLoS Med 2019 07 2;16(7):e1002847. Epub 2019 Jul 2.

Centre de recherche du Centre hospitalier de l'Université de Montréal, Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.

Background: The identification of patients with high-risk prostate cancer (PC) is a major challenge for clinicians, and the improvement of current prognostic parameters is an unmet clinical need. We and others have identified an association between the nuclear localization of NF-κB p65 and biochemical recurrence (BCR) in PC in small and/or single-centre cohorts of patients.

Methods And Findings: In this study, we accessed 2 different multi-centre tissue microarrays (TMAs) representing cohorts of patients (Test-TMA and Validation-TMA series) of the Canadian Prostate Cancer Biomarker Network (CPCBN) to validate the association between p65 nuclear frequency and PC outcomes. Immunohistochemical staining of p65 was performed on the Test-TMA and Validation-TMA series, which include PC tissues from patients treated by first-line radical prostatectomy (n = 250 and n = 1,262, respectively). Two independent observers evaluated the p65 nuclear frequency in digital images of cancer tissue and benign adjacent gland tissue. Kaplan-Meier curves coupled with a log-rank test and univariate and multivariate Cox regression models were used for statistical analyses of continuous values and dichotomized data (cutoff of 3%). Multivariate analysis of the Validation-TMA cohort showed that p65 nuclear frequency in cancer cells was an independent predictor of BCR using continuous (hazard ratio [HR] 1.02 [95% CI 1.00-1.03], p = 0.004) and dichotomized data (HR 1.33 [95% CI 1.09-1.62], p = 0.005). Using a cutoff of 3%, we found that this biomarker was also associated with the development of bone metastases (HR 1.82 [95% CI 1.05-3.16], p = 0.033) and PC-specific mortality (HR 2.63 [95% CI 1.30-5.31], p = 0.004), independent of clinical parameters. BCR-free survival, bone-metastasis-free survival, and PC-specific survival were shorter for patients with higher p65 nuclear frequency (p < 0.005). As the small cores on TMAs are a limitation of the study, a backward validation of whole PC tissue section will be necessary for the implementation of p65 nuclear frequency as a PC biomarker in the clinical workflow.

Conclusions: We report the first study using the pan-Canadian multi-centre cohorts of CPCBN and validate the association between increased frequency of nuclear p65 frequency and a risk of disease progression.
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http://dx.doi.org/10.1371/journal.pmed.1002847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605640PMC
July 2019

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A Population-Based Cohort Study.

Drug Saf 2019 08;42(8):1005-1011

Center for Clinical Epidemiology, Jewish General Hospital, Lady Davis Institute, 3755 Côte Sainte-Catherine, H-425.1, Montreal, QC, H3T 1E2, Canada.

Introduction: Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer.

Patients And Methods: We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings.

Results: The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49-1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses.

Conclusion: In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer.
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http://dx.doi.org/10.1007/s40264-019-00847-wDOI Listing
August 2019

Multimodal Prehabilitation to Enhance Functional Capacity Following Radical Cystectomy: A Randomized Controlled Trial.

Eur Urol Focus 2021 Jan 8;7(1):132-138. Epub 2019 Jun 8.

Division of Urology, Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Background: In patients with bladder cancer, poor functional status has remarkable deleterious effects on postoperative outcome and prognosis. Conditioning intervention initiated before surgery has the potential to reduce functional decline attributable to surgery. Nonetheless, evidence is lacking in patients undergoing radical cystectomy.

Objective: To determine whether a preoperative multimodal intervention (prehabilitation) is feasible and effective in radical cystectomy.

Design, Setting, And Participants: This study, conducted at an academic tertiary health care institution, enrolled adult patients scheduled for radical cystectomy. From August 2013 to October 2017, 70 patients were randomized: 35 to multimodal prehabilitation (prehab group) and 35 to standard care (control group).

Intervention: Multimodal prehabilitation was a preoperative conditioning intervention including aerobic and resistance exercise, diet therapy, and relaxation techniques.

Outcome Measurements And Statistical Analysis: Primary outcome was perioperative change in functional capacity, measured with the distance covered during a 6-min walk test (6MWD), assessed at baseline, before surgery, and at 4 and 8 wk after surgery. Data were compared using robust mixed linear models for repeated measures.

Results And Limitations: Preoperative change in 6MWD compared with baseline was not significantly different between groups (prehab group 40.8 [114.0] m vs control group 9.7 (108.4) m, p=0.250). However, at 4 wk after surgery, a significant difference in functional capacity was detected (6MWD, prehab group -15.4 [142.5] m vs control group -97.9 [123.8] m, p=0.014). No intervention-related adverse effects were reported.

Conclusions: Data suggested that multimodal prehabilitation resulted in faster functional recovery after radical cystectomy.

Patient Summary: After major cancer surgery, people usually feel week and tired, and have less energy to perform activities of daily living. In this study, we showed that using the time before surgery to promote exercise and good nutrition could fasten recovery after the surgical removal of the bladder.
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http://dx.doi.org/10.1016/j.euf.2019.05.016DOI Listing
January 2021

Cancer Drug Use in the Last Month of Life in Men With Castration-Resistant Prostate Cancer.

J Oncol Pract 2019 06 20;15(6):e510-e519. Epub 2019 May 20.

1 McGill University, Montreal, Quebec, Canada.

Purpose: Several new drug therapies have been approved in CRPC in the past decade. However, little is known about their potential overuse at the end of life. Cancer therapy use at the end of life has been considered an indicator of overtreatment. The study objective was to describe CRPC drug use in the last month of life of CRPC patients in Quebec.

Patients And Methods: Using administrative databases from the province of Quebec in Canada, we identified patients who received medical or surgical castration treatment, received one or more CRPC drugs (chemotherapy, abiraterone, or bone-targeted therapy), and died between 2001 and 2013. CRPC drug use in the last month of life was the primary outcome.

Results: The cohort consisted of 1,148 patients with CRPC. A total of 316 men (27.5%) received a CRPC drug in the last month of life. For those who received chemotherapy, abiraterone, and bone-targeted therapy, 10.2%, 27.8%, and 31.8% received them in the last month of life, respectively. In multivariable analyses, age older than 75 years (odds ratio [OR], 0.75; 95% CI, 0.57 to 0.99), and prostate cancer diagnosis received less than 24 months earlier (OR, 0.43; 95% CI, 0.26 to 0.72) were associated with less CRPC drug use. Relative to dying between 2005 and 2011, dying between 2012 and 2013 (OR 1.60; 95% CI, 1.18 to 2.18) was associated with greater CRPC drug use.

Conclusion: More than one quarter of patients received CRPC drug therapies in the last month of life. Persistent chemotherapy, abiraterone, bone-targeted therapies, and medical castration drugs in the last month of life may be an indicator of inappropriate and expensive end-of-life care.
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http://dx.doi.org/10.1200/JOP.18.00626DOI Listing
June 2019

Impact of the introduction of novel hormonal agents on metastatic castration-resistant prostate cancer treatment choice.

J Oncol Pharm Pract 2020 Mar 18;26(2):293-305. Epub 2019 Apr 18.

Faculty of Pharmacy, University of Montreal, Montreal, Canada.

Background: Docetaxel-based chemotherapy has been the cornerstone of the management of symptomatic metastatic castration-resistant prostate cancer (mCRPC) since 2004. This study aimed to describe how real-world clinical practice was changed with the public funding of novel hormonal agents (abiraterone and enzalutamide) in Quebec.

Methods: We conducted a retrospective cohort study in two McGill University hospitals. Hospital-based cancer registries were used to select mCRPC patients in medical oncology departments from January 2010 to June 2014. Two groups according to mCRPC diagnosis year were built, with 2012 chosen as the cut-off year, corresponding to the year abiraterone was approved for public reimbursement in second-line in Quebec. Kaplan-Meier analysis was used to estimate time to first docetaxel prescription since mCRPC diagnosis before and after 2012. Cox regression was used to identify predictive factors of docetaxel and novel hormonal agent use.

Results: In our cohort, 308 patients diagnosed with mCRPC were selected with 162 patients in the pre-2012 group and 146 patients in the post-2012 group. The median age at mCRPC was 74.0 years old. At 12 months from diagnosis, 69% of patients received a prescription for docetaxel in the pre-2012 group comparatively to 53% in the post-2012 group. Factors that decreased the likelihood of docetaxel utilization were: age older than 80 at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3-0.7), mCRPC diagnosis after 2012 (HR: 0.6; 95%CI: 0.4-0.8), and asymptomatic disease at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3-0.7).

Conclusion: The introduction of novel hormonal agents reduced first-line and overall docetaxel utilization and delayed time to its initiation.
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http://dx.doi.org/10.1177/1078155219842329DOI Listing
March 2020

Short- and long-term survival has improved after radical cystectomy for bladder cancer in Québec during the years 2000-2015.

J Surg Oncol 2019 Jun 28;119(8):1135-1144. Epub 2019 Mar 28.

Department of Surgery, McGill University Health Centre, Montreal, Québec, Canada.

Background And Objectives: We evaluated the short- and long-term outcome in bladder cancer (BC) patients treated with radical cystectomy (RC) in Québec (Canada).

Methods: Data were collected from provincial registries on all BC patients who underwent RC in Québec province in 2000-2015. Outcomes were hospitalization rates and survival. Survival analyses were conducted using log-rank tests and Cox proportional hazards models.

Results: In total, 4450 patients were included in our analysis. RC was increasingly conducted by higher-volume surgeons in larger, higher-volume, academic hospitals. Comparing patients treated in 2010-2015 to 2000-2009, recently treated patients had shorter postoperative hospital stays (absolute difference, 0.9 days, P < 0.001) but also a higher readmission rate (25.0% vs 21.1% in the 30 days following discharge, P = 0.003). Overall (5-year rates 50.9% vs 42.7%, P < 0.001) and BC-specific survival (61.3% vs 55.5%, P < 0.001) had significantly improved. In multivariable analyses, overall survival was significantly better in recently treated patients (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.60-0.73), younger patients (HR, 1.16; 95% CI, 1.14-1.19), patients residing closer to the hospital (HR, 1.03; 95% CI, 1.01-1.06), and patients treated by high-volume surgeons (HR, 0.88; 95% CI, 0.82-0.94).

Conclusions: Survival in BC patients after RC has improved in recent years. Other predictors for survival are younger age, shorter distance between patients' residences and hospitals, and higher surgeon's RC loads.
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http://dx.doi.org/10.1002/jso.25456DOI Listing
June 2019

Psychosocial adjustment to a prostate cancer diagnosis in a cohort of radical prostatectomy patients in Quebec, Canada.

Psychooncology 2019 04 27;28(4):839-846. Epub 2019 Feb 27.

Division of Urology, Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada.

Objective: The psychosocial impact of a prostate cancer diagnosis significantly affects a patient's quality of life. We studied patient communication at the time of diagnosis and its impact on psychosocial adjustment of patients.

Methods: This is a cross-sectional data analysis from self-administered questionnaires in the PROCURE biobank study, consisting of a cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec (Canada), 2006 to 2013. Odds ratios (OR) and their respective 95% confidence intervals (95% CI) were calculated using binary or ordered logistic regression models.

Results: Data from 1841 patients were analyzed. The median age of patients was 62 years (range 41-80 years), the majority was French-Canadian (68.3%) and married (79.6%). Most patients (90.1%) considered conversations with their treating physician a useful information source. Patients were dissatisfied on the communication when receiving their diagnosis by telephone (OR = 0.19, 95% CI, 0.11-0.33). Younger patients were also more dissatisfied. Most patients preferred to receive information on prostate cancer (89.5%) and radical prostatectomy (88.0%) at the time of diagnosis, while only 58.8% and 52.4% of patients received this information at this stage. Patients who were dissatisfied with the communication of the diagnosis had more negative responses, such as increased worries and fear (P < 0.05). The five most useful coping mechanisms were physical activity (62.3%), breathing exercises (44.5%), music (32.8%), faith (30.3%), and muscle relaxation (30.1%), but varied by demographics.

Conclusions: This study highlights the importance of physicians communicating a prostate cancer diagnosis well to their patients. Patients may benefit from individually tailored interventions to facilitate their overall coping.
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http://dx.doi.org/10.1002/pon.5031DOI Listing
April 2019

A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer.

Cancer Epidemiol Biomarkers Prev 2019 04 7;28(4):701-706. Epub 2019 Feb 7.

CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, Canada.

Background: In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression.

Methods: The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.

Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 ( = 0.0017; q = 0.026) and 1.24 ( = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; = 0.057) and DHEA-S levels (HR = 1.43; = 0.054).

Conclusions: In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.

Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1002DOI Listing
April 2019

Evaluation of New Tests and Interventions for Prostate Cancer Management: A Systematic Review.

J Natl Compr Canc Netw 2018 11;16(11):1340-1351

Inaccurate risk classification and the burden of unnecessary biopsies are a challenge due to the limited ability of current risk assessment tools and modalities to diagnose prostate cancer (PCa) and distinguish indolent from aggressive disease. This systematic review assesses newly developed tests and interventions with high evidence of clinical utility that might be adopted in clinical practice during PCa management before initial and repeat biopsy, after positive biopsy, and after radical treatment. The Cochrane, Embase, MEDLINE, and Web of Science databases were searched for studies pertaining to the clinical utility of PCa diagnostic tests. Outcomes of interest were (1) a measure of the percentage of altered decision-making, (2) decrease in number of unnecessary biopsies, (3) decrease or increase in treatment intensity, and (4) risk reclassification after test results. The search yielded 2,940 articles, of which 46 met the inclusion criteria. We found clinical utility evidence on the Prostate Health Index (PHI), 4Kscore test, MRI, OncotypeDX, Decipher test, Prolaris, ConfirmMDx, Progensa PCA3, NADiA ProsVue, and ProMark. No evidence was identified for Prostarix, ProstaVysion, Prostate Core Mitomic Test, and Mi-Prostate Score. The interventions demonstrated their clinical utility in terms of change in treatment recommendations, decrease/increase in interventional treatment, decrease in biopsy, and risk reclassification. At diagnosis after a positive biopsy, ProMark, OncotypeDX, Prolaris, and MRI guided the use of active surveillance. Use of NADiA ProsVue, Decipher, and Prolaris aided in the decision to add adjuvant therapy post-prostatectomy. PHI, 4Kscore, and MRI used prior initial and repeat biopsies, and ConfirmMDx and Progensa PCA3 used prior repeat biopsies to improve prediction of biopsy outcome, allowing a decrease in unnecessary biopsies. This systematic review suggests that implementation of these tests in clinical practice could effectuate personalized treatment of PCa. Further clinical and economic evaluation studies of long-term PCa outcomes are warranted to provide further guidance.
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http://dx.doi.org/10.6004/jnccn.2018.7055DOI Listing
November 2018

The Terry Fox Research Institute Canadian Prostate Cancer Biomarker Network: an analysis of a pan-Canadian multi-center cohort for biomarker validation.

BMC Urol 2018 Sep 10;18(1):78. Epub 2018 Sep 10.

Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal, 900, St-Denis St, room R10-464, Montréal, Québec, H2X 0A9, Canada.

Background: Refinement of parameters defining prostate cancer (PC) prognosis are urgently needed to identify patients with indolent versus aggressive disease. The Canadian Prostate Cancer Biomaker Network (CPCBN) consists of researchers from four Canadian provinces to create a validation cohort to address issues dealing with PC diagnosis and management.

Methods: A total of 1512 radical prostatectomy (RP) specimens from five different biorepositories affiliated with teaching hospitals were selected to constitute the cohort. Tumoral and adjacent benign tissues were arrayed on tissue microarrays (TMAs). A patient clinical database was developed and includes data on diagnosis, treatment and clinical outcome.

Results: Mean age at diagnosis of patients in the cohort was 61 years. Of these patients, 31% had a low grade (≤6) Gleason score (GS), 55% had GS 7 (40% of 3 + 4 and 15% of 4 + 3) and 14% had high GS (≥8) PC. The median follow-up of the cohort was 113 months. A total of 34% had a biochemical relapse, 4% developed bone metastasis and 3% of patients died from PC while 9% died of other causes. Pathological review of the TMAs confirmed the presence of tumor and benign tissue cores for > 94% of patients. Immunohistochemistry and FISH analyses, performed on a small set of specimens, showed high quality results and no biorepository-specific bias.

Conclusions: The CPCBN RP cohort is representative of real world PC disease observed in the Canadian population. The frequency of biochemical relapse and bone metastasis as events allows for a precise assessment of the prognostic value of biomarkers. This resource is available, in a step-wise manner, for researchers who intend to validate prognostic biomarkers in PC. Combining multiple biomarkers with clinical and pathologic parameters that are predictive of outcome will aid in clinical decision-making for patients treated for PC.
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http://dx.doi.org/10.1186/s12894-018-0392-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131811PMC
September 2018

The combination of PTEN deletion and 16p13.3 gain in prostate cancer provides additional prognostic information in patients treated with radical prostatectomy.

Mod Pathol 2019 01 23;32(1):128-138. Epub 2018 Aug 23.

Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Prostate cancer is a clinically heterogeneous disease and accurately risk-stratifying patients is a key clinical challenge. We hypothesized that the concurrent identification of the DNA copy number alterations 10q23.3 (PTEN) deletion and 16p13.3 (PDPK1) gain, related to the PI3K/AKT survival pathway, would improve prognostication. We assessed PTEN deletion status using fluorescence in situ hybridization (FISH) and evaluated its clinical significance in combination with the 16p13.3 gain in a set of 332 primary radical prostatectomy cases on a tissue microarray with clinical follow-up. The PTEN deletion was detected in 34% (97/287) of the evaluable tumors and was significantly associated with high Gleason grade group (P < 0.0001) and advanced pathological tumor stage (pT-stage, P < 0.001). The PTEN deletion emerged as a significant predictor of biochemical recurrence independent of the standard clinicopathologic parameters (hazard ratio: 3.00, 95% confidence interval: 1.81-4.98; P < 0.0001) and further stratified patients with low and intermediate risk of biochemical recurrence [Gleason grade group 1-2 (≤3 + 4), Gleason grade group 2 (3 + 4), pT2, prostate-specific antigen ≤ 10, low and intermediate CAPRA-S score; log-rank P ≤ 0.007]. A PTEN deletion also increased the risk of distant metastasis (log-rank, P = 0.001), further supporting its role in prostate cancer progression. Combining both 16p13.3 gain and PTEN deletion improved biochemical recurrence risk stratification and provided prognostic information beyond the established CAPRA-S score (co-alteration: hazard ratio: 4.70, 95% confidence interval: 2.12-10.42; P < 0.0001). Our study demonstrates the potential clinical utility of PTEN genomic deletion in low-intermediate risk patients and highlights the enhanced prognostication achieved when assessed in combination with another genomic biomarker related to the PI3K/AKT pathway, thereby supporting their promising usefulness in clinical management of prostate cancer.
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http://dx.doi.org/10.1038/s41379-018-0107-6DOI Listing
January 2019
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