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

ABSTRACT: 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.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.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.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.

SUBMITTER: Ouellet V

PROVIDER: S-EPMC6131811 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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

Ouellet Véronique V Aprikian Armen A Bergeron Alain A Brimo Fadi F Bristow Robert G RG Chevalier Simone S Drachenberg Darrel D Fazli Ladan L Fleshner Neil E NE Gleave Martin M Karakiewicz Pierre P Klotz Laurence L Lacombe Louis L Lattouf Jean-Baptiste JB van der Kwast Theodorus T Squire Jeremy A JA Latour Mathieu M Trudel Dominique D Mes-Masson Anne-Marie AM Saad Fred F

BMC urology 20180910 1

<h4>Background</h4>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.<h4>Methods</h4>A total of 1512 radical prostatectomy (RP) specimens from five different biorepositories affiliated with teaching hospital ...[more]

PMID: 30200929

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Project description: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.

Dataset Information

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

Publications

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

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