Biopsies don’t tell the whole story. False negatives are common with initial and follow-up biopsies. Each core represents As many as 1/2000 30% of a normal size prostate (30 g). of initial negatives prove to be positive on repeat biopsies. Patients with false negatives are managed in the same manner as those with true negatives. What if you could determine the difference between a false negative and a true negative? Now you can with the Prostate Core Mitomic Test. Patient A Negative PCMT Result Age 62, persistently rising PSA, family history Biopsy outcome Request PCMT Confirm a true negative with 92% negative predictive value. Patient B Positive PCMT Result Age 62, persistently rising PSA, family history Biopsy outcome Request PCMT Identify patients at high risk for undiagnosed prostate cancer with 85% sensitivity. Confidently stratify your patients. Negative PCMT result Positive PCMT result • Be more confident in negative results. • Detect undiagnosed prostate cancer early. • Provide peace of mind to patients. • Manage patient based on positive PCMT result and additional risk factors. • Avoid causing patients added pain, anxiety, and risk from unnecessary, extra biopsies. • Tailor patient management for improved patient care. Patient Selection Clinical Response Positive biopsy outcome (30%) PCMT negative outcome PSA > 4.0 ng/ml PSADT < 3 months PSAV > 0.4 ng/ml/year Negative biopsy outcome (70%) Patient currently at low risk of undiagnosed prostate cancer. Defer repeat biopsy and routine screening 12 to 14 months. Life Expectancy > 10 years ASAP HGPIN Family History African American PCMT positive outcome Patient is at high risk for undiagnosed prostate cancer. A repeat biopsy is recommended with presence of additional risk factors. Tumor field effect Tumor field effect • Identifies a large-scale deletion in mitochondrial DNA that indicates cellular change associated with undiagnosed prostate cancer. • Detects presence of malignant cells in normal appearing tissue across an extended area. Why mitochondrial DNA? The Prostate Core Mitomic Test detects largescale mtDNA deletion to discriminate between benign and malignant prostate tissue. Why mitochondrial DNA (mtDNA)? • Mass copy rate allows for the most extensive field effect possible. • Mutations associated with prostate cancer appear in tumors and normal tissue. • High susceptibility to damage enables unprecedented early disease detection. Key Data Review Powerful differentiator of malignant and nonmalignant prostate tissue (p<0.0001) Demographics Patients 183 Total biopsy cores 296 Age 67.05 • Deletion accurately discriminates between biopsies having prostate cancer and those without (AUC 0.83) • Non-malignant pathologies (HGPIN, atrophy, etc) do not confound this discriminatory power.* Maki J, et al. Mitochondrial Genome Deletion Aids in the Identification of False- and True-Negative Prostate Needle Core Biopsy Specimens. American Journal of Clinical Pathology. 2008; 129:57-66. Accurate predictor of repeat biopsy outcomes Demographics Patients 101 Total biopsy cores 595 Age 60.64 PSA 7.09 ng/ml Interval between biopsy Up to 14 months • Identifies men who do not require biopsy with a high degree of certainty (SE 85%, SP 54%; NPV 92%; false negative rate 15%) Robinson K, Creed J, Reguly B, Powell C, Wittock R, Klein D, et al. Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate cancer and prostatic diseases. 2010;13(2):126-31 Disease specific with extensive tumor field Method Purpose Result 19 radical prostatectomies with peripheral, unifocal low volume tumor Assess biomarker frequency at increasing distance from tumor All cores were positive for biomarker which confirms the great extent of the tumor field 26 cystoprostatecomies – malignancy in bladder but not in prostate gland Determine frequency in cystoprostatectomies where malignancy was not found in prostate Low quantity of biomarker supports specificity of biomarker for prostate cancer negative result on all specimens which confirms biomarker is prostate cancer specific 21 malignant seminal vesicles from malignant prostatectomies Determine frequency in malignant seminal vesicles taken during prostatectomy Low volume of biomarker supports tissue specificity for prostate cancer 21 benign seminal vesicles from malignant prostatectomies Determine frequency in benign seminal vesicles taken during prostatectomy Low volume of biomarker supports tissue specificity for prostate cancer Mills et al. Large-Scale 3.4kb Mitochondrial Genome Deletion is Significantly Associated with a Prostate Cancer Field Effect. Poster presented as part of the American Urological Association Annual Meeting, San Diego, CA, May 4-8, 2013. Journal of Urology, Vol. 189, No. 4S, Supplement e604, May 2013. Parr RL, Jakupciak JP, Reguly B, and Dakubo GD. 3.4kb Mitochondrial Genome Deletion Serves as a Surrogate Predictive Biomarker for Prostate Cancer in Histopathologically Benign Biopsy Cores. Canadian Urological Association Journal. 2010. Demographics Case 2 Patients 4 Age 65 Total biopsy 2-4/patient PSA 8.9 ng/ml Initial negative biopsy Yes Biopsy 1 Negative (9 cores) Positive repeat biopsy Yes (3) Biopsy 2 (7 months) Negative (10 cores) Predicted malignant outcome 11, 21 and 31 months in advance of RP Biopsy 3 (1 year) Positive for prostate cancer in LB / HGPIN in RB Benign outcome confirmed 60 months in advance of follow up biopsy RP (2 months) Tumor involvement in both L&R lobes. Largest mass in LM. Cores from LM in all 3 biopsies returned negative. PCMT performed on initial biopsy Positive for biomarker 21 months in advance of RP. Identified in LM. Appendix Published data • John Mills, Luis Martin, François Guimont, Brian Reguly, Andrew Harbottle, John Pedersen, Jennifer Creed, Ryan Parr. Large-Scale 3.4kb Mitochondrial Genome Deletion is Significantly Associated with a Prostate Cancer Field Effect. Poster presented as part of the American Urological Association Annual Meeting, San Diego, CA, May 4-8, 2013. Abstract published in Journal of Urology, Vol. 189, No. 4S, Supplement e604, May 2013. • Ryan Parr, John Mills, Andrew Harbottle, Jennifer Creed, Gregory Crewdson, Brian Reguly, Francois Guimont. Mitochondria, Prostate Cancer and Biopsy Sampling Error. Discovery Medicine, Volume 15, Number 83, April 2013. • Parr and Martin: Mitochondrial and nuclear genomics and the emergence of personalized medicine. Human Genomics 2012 6:3. • Kent Froberg, Laurence Klotz, Kerry Robinson, Jennifer Creed, Brian Reguly, Cortney Powell, Daniel Klein, Andrea Maggrah, Roy Wittock, Ryan Parr. Large-scale mitochondrial genome deletion as an aid for negative prostate biopsy uncertainty. Poster presented as a part of the American Urological Association Annual Meeting, Washington, D.C., May 14-19, 2011. Abstract published in The Journal of Urology, Vol. 185 No. 4S, e 764, Supplement, May 2011. • Ryan Parr, Jennifer Creed, Brian Reguly, Cortney Powell, Roy Wittock, Daniel Klein, Andrea Maggrah, Kerry Robinson* Large-scale mitochondrial genome deletion as an aid for negative prostate biopsy uncertainty. Poster presented as part of the Society of Urologic Oncology Annual Meeting, Bethesda, MD, Dec. 8-10, 2010. Published data • • • • • • • Parr RL, Jakupciak JP, Reguly B, and Dakubo GD. 3.4kb “Mitochondrial Genome Deletion Serves as a Surrogate Predictive Biomarker for Prostate Cancer in Histopathologically Benign Biopsy Cores.” Canadian Urological Association Journal. 2010. Robinson K, Creed J, Reguly B, Powell C, Wittock R, Klein D, et al. Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate cancer and prostatic diseases. 2010;13(2):126-31. Epub 2010/01/20. Parr RL, Jakupciak JP, Birch-Machin MA, Dakubo GD. The Mitochondrial Genome: A Biosensor for Early Cancer Detection? Expert Opin Med Diagn. 2007;1(2):169-82. Maki J, Robinson K, Reguly B, Alexander J, Wittock R, Aguirre A, et al. Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens. American journal of clinical pathology. 2008;129(1):57-66. Epub 2007/12/20. Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL. Clinical Implications and Utility of Field Cancerization. Cancer Cell International. 2007;7(2). Parr RL, Dakubo GD, Crandall KA, Maki J, Reguly B, Aguirre A, et al. Somatic mitochondrial DNA mutations in prostate cancer and normal appearing adjacent glands in comparison to age-matched prostate samples without malignant histology. The Journal of molecular diagnostics : JMD. 2006;8(3):312-9. Epub 2006/07/11. Parr RLM, J.; Reguly, B.; Dakubo, G.D.; Aguirre, A.; Wittock, R.; Robinson, K.; Jakupciak,J.P.;Thayer, R.E. The pseudo-mitochondrial genome influences mistakes in heteroplasmy interpretation. BMC Genomics. 2006;21(7). Thank you Prostate Core Mitomic Test or one or more of its components was developed and its performance characteristics determined by Mitomics. It has not been approved by the Food and Drug Administrative (FDA). Mitomics has determined that such approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research purposes. Mitomics is regulated under the Clinical Laboratory Improvement Act of 1988 as qualified to perform high-complexity clinical testing. Prostate Core Mitomic Test, Mitomics, Mitomic Technology, Now You Can Know and Empowering Clinical Insight are trademarks of Mitomics Inc. © 2013 Mitomics Inc. All rights reserved.