Biomarkers for Risk Stratification in Prostate Cancer

David M. Berman, MD, PhDProfessor of Pathology and

Molecular Medicine

Prostate cancer

2nd

most common non-skin cancer

Only 15%

die of this disease2

Natural history of untreatedprostate 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; 367:203-213

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;33:272-277

Diagnosed with pure low grade prostate cancer?

Diagnosed with harmless prostate cancer?

Biopsy sampling error

Biopsy sampling error

Pathologist disagreement

Biomarkers for prostate cancer

23

Phenotypic Genotypic

Biomarkers for prostate cancer

24

Phenotypic Genotypic

Loss of tumour suppressor PTEN

PTEN is a genotypic biomarker

Grades

Lotan et al., Mod Pathol. 2015 Jan;28(1):128

Biomarkers for prostate cancer

27

GenotypicGenotypic

Gene silencing is common in prostate cancer

Elevated DNA methylation levels are present in intermediate grade cancer

Low Low + High grade29

Elevated DNA methylation levels are present in intermediate grade cancer

Low Low + High grade30

Training CohortValidation Cohort

Current work

31

CCDC181 RASSF1A GSTP1 ABCB1

EDNRB GSTM2 ALDH1A2 MT1M

GAS6 HAPLN3

VALIDATE

GOAL: Develop a biomarker for prostate biopsies32

Personalised Risk stratificatiOn for patieNts wiTh prOstate cancer: PRONTO

PRONTO project

400

Gen

e Pa

nel Stromal Signaling

Cancer Metabolism

Epithelial Plasticity

Copy number variants

DNA methylation

PRONTO project

400

Gen

e Pa

nel Stromal Signaling

Cancer Metabolism

Epithelial Plasticity

Copy number variants

DNA methylation

PRONTO project

35

McGill CohortQueen’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