PCMT PowerPoint September 2013

False negatives are common

with initial and follow-up biopsies.

Patients with false negatives are

managed in the same manner as

those with true negatives.

Biopsies

don’t tell

the whole

story.

Each core represents

1/2000 of a normal size

prostate (30 g).

As many as

30%of initial negatives

prove to be positive

on repeat biopsies.

What if you could determine

the difference between a false

negative and a true negative?

Now you can with the

Prostate Core Mitomic Test.

Negative PCMT Result

Confirm a true negative with

Patient A

Request PCMT

Age 62, persistently rising PSA, family history

Biopsy outcome

92%negative predictive value.

Patient B

Request PCMT

Age 62, persistently rising PSA, family history

Positive PCMT Result

85%sensitivity.

Identify patients at high risk for

undiagnosed prostate cancer with Biopsy outcome

Confidently stratify

your patients.

Negative PCMT result

• Be more confident in

negative results.

• Provide peace of mind

to patients.

• Avoid causing patients added

pain, anxiety, and risk from

unnecessary, extra biopsies.

• Detect undiagnosed

prostate cancer early.

• Manage patient based on

positive PCMT result and

additional risk factors.

• Tailor patient management

for improved patient care.

Positive PCMT result

Patient Selection Clinical Response

Positive biopsy

outcome (30%)

Negative biopsy

outcome (70%)

PSA > 4.0 ng/ml

PSADT < 3

months

PSAV > 0.4

ng/ml/year

Life Expectancy >

10 years

ASAP

HGPIN

Family History

African American

PCMT negative outcome

Patient currently at low risk of

undiagnosed prostate cancer.

Defer repeat biopsy and

routine screening 12 to 14

months.

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?

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.

The Prostate Core Mitomic Test detects large-

scale mtDNA deletion to discriminate between

benign and malignant prostate tissue.

Data Review

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

Demographics Performance

Patients 101 Predicted positive outcome

in 17/20 patients

Total biopsy

cores

595 SN 85%

Age 60.64 NPV 92%

PSA 7.09 ng/ml

Interval between

biopsy

7.72

months

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.

John 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.

Method Purpose Result

16 radical prostatectomies

with peripheral, unifocal low

volume tumor

12 successive

cores removed

across axial plane

Assess biomarker frequency at

increasing distance from tumor

All cores both histologically malignant and

benign were called positive for biomarker

which confirms the tumor field effect is gland

wide

26 cystoprostatecomies –

malignancy in bladder but not

in prostate gland

Single core

removed

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

Single core

removed

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

Single core

removed

Determine frequency in benign

seminal vesicles taken during

prostatectomy

Low volume of biomarker supports tissue

specificity for prostate cancer

Appendix

Stages of Development

The entire process of discovery and validation involved 396 patients and close to

1,700 prostate core samples. Included were 143 patients with benign histology and

253 patients with malignant histology. Stage 2 involved an external validation study

performed by the National Institute of Standards and Technology under the Early

Detection Research Network of the National Cancer Institute (NCI). Stage 3 was

conducted within the framework of a clinical trial.

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.

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