Biomarkers for Risk Stratification in Prostate Cancer David M. Berman, MD, PhD Professor of Pathology and Molecular Medicine.

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Presentation transcript:

Biomarkers for Risk Stratification in Prostate Cancer David M. Berman, MD, PhD Professor of Pathology and Molecular Medicine

Prostate cancer 2 nd most common non-skin cancer Only 15% die of this disease 2

Natural history of untreated prostate cancer

PSA screening 4

Biopsy 5

Progress in Prostate Cancer Control cdc.gov

CRISIS

Canadian Task Force Bell et al., CMAJ 2014; 186:1225

Does screening save lives? Moyer V et al. Ann Int Med 2012; 157:120

Treatment benefit correlates with risk of progression Wilt et al., NEJM 2012; 367:

Low grade prostate cancer

Grading prostate cancer

“True” grade predicts survival

High grade cancer is lethal

Let’s not treat low grade cancers NEARLY 1/2

“Active Surveillance”

Attrition on Active Surveillance Laurence Klotz et al. JCO 2015;33:

Diagnosed with pure low grade prostate cancer?

Diagnosed with harmless prostate cancer?

Biopsy sampling error

Pathologist disagreement

Biomarkers for prostate cancer 23 PhenotypicGenotypic

Biomarkers for prostate cancer 24 PhenotypicGenotypic

Loss of tumour suppressor PTEN

PTEN is a genotypic biomarker Lotan et al., Mod Pathol Jan;28(1):128

Biomarkers for prostate cancer 27 Genotypic

Gene silencing is common in prostate cancer

Elevated DNA methylation levels are present in intermediate grade cancer LowLow + High grade 29

Elevated DNA methylation levels are present in intermediate grade cancer LowLow + High grade 30 Training Cohort Validation Cohort

Current work 31 VALIDATE

GOAL: Develop a biomarker for prostate biopsies 32 Personalised Risk stratificatiOn for patieNts wiTh prOstate cancer: PRONTO

PRONTO project

35 McGill Cohort Queen’s Cohort Discovery Validation

Thanks 36 Urology Rob Siemens Chris Doiron Pathology Sandy Boag Chris Davidson Marosh Manduch Zanobia Khan Berman Lab Atsunari Kawashima John Okello Palak Patel Tamara Jamaspishvili Nathan How Suzanne Boursalie