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

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

3. Natural history of untreated prostate cancer

4. PSA screening 4

5. Biopsy 5

6. Progress in Prostate Cancer Control cdc.gov

7. CRISIS

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

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

10. Treatment benefit correlates with risk of progression Wilt et al., NEJM 2012; 367:203-213

11. Low grade prostate cancer

12. Grading prostate cancer

13. “True” grade predicts survival

14. High grade cancer is lethal

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

16. “Active Surveillance”

17. Attrition on Active Surveillance Laurence Klotz et al. JCO 2015;33:272-277

18. Diagnosed with pure low grade prostate cancer?

19. Diagnosed with harmless prostate cancer?

20. Biopsy sampling error

22. Pathologist disagreement

23. Biomarkers for prostate cancer 23 PhenotypicGenotypic

24. Biomarkers for prostate cancer 24 PhenotypicGenotypic

25. Loss of tumour suppressor PTEN

26. PTEN is a genotypic biomarker Lotan et al., Mod Pathol. 2015 Jan;28(1):128

27. Biomarkers for prostate cancer 27 Genotypic

28. Gene silencing is common in prostate cancer

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

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

31. Current work 31 VALIDATE

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

33. PRONTO project

35. 35 McGill Cohort Queen’s Cohort Discovery Validation

36. 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​​