A Gene Expression Test to
Predict Prostate Cancer
Aggressiveness
Use Prolaris® testing as a guide in your medical
and surgical management
A prognostic medicine product for prostate cancer.
What is Prolaris®?
Prostate cancer (PCa) is now the second most frequently diagnosed cancer and the
sixth most common cause of cancer-related mortality in men worldwide.1
• A novel genetic test developed to help doctors predict prostate cancer aggressiveness, together with other
clinical variables
• A direct molecular measure of prostate cancer tumor biology
• An RNA expression signature based on cell cycle progression (CCP) genes
An estimated 1.1 million men were diagnosed with prostate cancer across the world in
2012.2 Only 3% of men diagnosed with prostate cancer will die from it.3
Prostate cancer natural history is highly variable and difficult to predict, with most men
• A 46 gene panel and integrative algorithms to assess prostate cancer aggressiveness
- 31 genes across multiple cell cycle progression pathways
- 15 housekeeper genes
• Prolaris testing results provides a Prolaris ScoreTM. Prolaris Scores can range from -3 to 7 (technical range).
Each 1-unit increase in the Prolaris Score represents a doubling (or halving) of risk. Higher Prolaris Scores
having indolent disease that could be safely followed without immediate treatment,
and others having a more aggressive disease requiring immediate intervention.
represent more aggressive cancers
• Prolaris testing can be done:
- following affirmative biopsy and prostate cancer diagnosis
Prolaris® (also called CCP in clinical publications) is the first prognostic test that offers a
- following radical prostatectomy
look inside the molecular biology of prostate cancer to help physicians determine its
• Prolaris testing provides greater prognostic information than Gleason score or PSA
aggressiveness. In combination with other variables, such as Gleason score and PSA,
Prolaris provides a personalized assessment of risk.
• Prolaris testing provides personalized risk assessment:
- prognostic for biochemical recurrence (BCR), metastasis and PCa mortality
THE PROLARIS 46-GENE PANEL
FOXM1
COC20
COKN3
COC2
KIF11
KIAA0101
NUSAP1
CENPF
ASPM
BUB1B
RRM2
DULGAPS
BIRCS
KIF20A[BP1]
PLK1
TOP2A
TK1
PBK
ASF1B
C18or∫24
RAD54L
PTTG1
MCM10
PRC1
DTL
CEP55
RAD51
CENPM
COCA3
COCA8
ORC6L
A prognostic medicine product for prostate cancer.
31 Cell Cycle Progression Genes
Highly correlated and provide
a reproducible measure of cell
proliferation
RPL38
RPL4
SLC25A3
PSMA1
RPL13A
UBA52
RPL37
CLTC
RPL8
PPP2CA
PSMC1
RPS29
TXNL1
MMADHC
MRFAP1
15 Housekeeper Genes
Normalize the expression of the
cell proliferation genes
Prolaris® provides unique and independent information from current
clinical and pathological features
What is Prolaris®?
Prostate cancer (PCa) is now the second most frequently diagnosed cancer and the
sixth most common cause of cancer-related mortality in men worldwide.1
• A novel genetic test developed to help doctors predict prostate cancer aggressiveness, together with other
clinical variables
• A direct molecular measure of prostate cancer tumor biology
• An RNA expression signature based on cell cycle progression (CCP) genes
An estimated 1.1 million men were diagnosed with prostate cancer across the world in
2012.2 Only 3% of men diagnosed with prostate cancer will die from it.3
Prostate cancer natural history is highly variable and difficult to predict, with most men
• A 46 gene panel and integrative algorithms to assess prostate cancer aggressiveness
- 31 genes across multiple cell cycle progression pathways
- 15 housekeeper genes
• Prolaris testing results provides a Prolaris ScoreTM. Prolaris Scores can range from -3 to 7 (technical range).
Each 1-unit increase in the Prolaris Score represents a doubling (or halving) of risk. Higher Prolaris Scores
having indolent disease that could be safely followed without immediate treatment,
and others having a more aggressive disease requiring immediate intervention.
represent more aggressive cancers
• Prolaris testing can be done:
- following affirmative biopsy and prostate cancer diagnosis
Prolaris® (also called CCP in clinical publications) is the first prognostic test that offers a
- following radical prostatectomy
look inside the molecular biology of prostate cancer to help physicians determine its
• Prolaris testing provides greater prognostic information than Gleason score or PSA
aggressiveness. In combination with other variables, such as Gleason score and PSA,
Prolaris provides a personalized assessment of risk.
• Prolaris testing provides personalized risk assessment:
- prognostic for biochemical recurrence (BCR), metastasis and PCa mortality
THE PROLARIS 46-GENE PANEL
FOXM1
COC20
COKN3
COC2
KIF11
KIAA0101
NUSAP1
CENPF
ASPM
BUB1B
RRM2
DULGAPS
BIRCS
KIF20A[BP1]
PLK1
TOP2A
TK1
PBK
ASF1B
C18or∫24
RAD54L
PTTG1
MCM10
PRC1
DTL
CEP55
RAD51
CENPM
COCA3
COCA8
ORC6L
A prognostic medicine product for prostate cancer.
31 Cell Cycle Progression Genes
Highly correlated and provide
a reproducible measure of cell
proliferation
RPL38
RPL4
SLC25A3
PSMA1
RPL13A
UBA52
RPL37
CLTC
RPL8
PPP2CA
PSMC1
RPS29
TXNL1
MMADHC
MRFAP1
15 Housekeeper Genes
Normalize the expression of the
cell proliferation genes
Prolaris® provides unique and independent information from current
clinical and pathological features
Prolaris: Extensive Validation in both Bio psy and Radical Prostatectomy Settings
A study of 582 patients evaluated the prognostic utility of the Prolaris Score derived from biopsy specimens
Prolaris Score
in men who were treated by radical prostatectomy. Results from this study indicate that Prolaris can be
TM
was found to be the strongest independent predictor of prostate cancer-related death
and provided more information than either Gleason score or PSA.4
used at disease diagnosis to better define patient prognosis and enable more appropriate clinical care.5
10-year Estimated Biochemical Recurrence Progression-free Survival
10-year Estimated Prostate Cancer Death According to Prolaris (CCP) Score
>3 (n=16)
2 to ≤ 3 (n=50)
1 to ≤ 2 (n=114)
75
• Study demonstrates that
0 to ≤ 1 (n=133)
CCP score ≤ 0 (n=36)
Prolaris (CCP) Score pre-
50
dicts survival from prostate cancer.
25
Biochemical Recurrence
Progression-free Survival
Death from prostate cancer (%)
1.0
CCP score
100
0.8
•Prolaris (CCP) Score corre0.6
lates with the probability of
biochemical recurrence and
0.4
CCP score
was the strongest predictor
-2 to ≤ 0 (n=316)
of metastatic disease.
0 to ≤ 1 (n=185)
0.2
1 to ≤ 2 (n=67)
2 to ≤ 3 (n=14)
0
0
0
2
4
6
8
10
0
2
4
Time since diagnosis (years)
6
8
10
Years after surgery
A study of 141 prostate cancer patients treated with external beam radiation therapy (EBRT) with curative
Scatter Plot of Predicted 10-year Risk of Death From
Prostate Cancer for Combined Risk Score versus
Clinical Risk Score*
intent evaluated whether Prolaris test can be used as a prognostic indicator. The study showed that Prolaris
was significantly predictive of biochemical recurrence.6
100
Scatter Plot of Predicted 5-year Risk of BCR for
Combined Risk vs Clinical Risk*
50
Gleason score and PSA values improves
20
the 10-year survival prediction compared
to clinical parameters alone. 10
*Different Gleason score categories are shown by different colored dots
(blue, Gleason <7; orange, Gleason =7; red, Gleason >7). For any given
patient, the added contribution of the cell cycle progression (CCP) score
to the predicted risk based on Gleason and prostate-specific antigen (PSA)
can be determined by the horizontal distance between the dot and the
diagonal dashed line.
5
2
2
5
10
20
50
Combined risk % (CCP + Gleason + PSA)
100
Clinical risk % (Gleason + PSA + Percent
positive cores + Concurrent hormone use)
• Combining Prolaris (CCP) Score with
100
50
• Prolaris (CCP) Score provided prognostic
information that was not provided by
20
standard clinical parameters.
10
• Prolaris adds further risk stratification over and
5
above that provided by clinical risk parameters
alone.
2
1
Gleason <7
Gleason =7
Gleason >7
0.5
0.5
1
2
5
10
20
50 100
Combined risk %
(CCP + Gleason + PSA + Percent positive cores
+ Concurrent hormone use)
*Different Gleason score categories are shown by different colored dots (blue,
Gleason <7; orange, Gleason =7; red, Gleason >7). For any given patient, the
added contribution of the cell cycle progression (CCP) score to the predicted risk
based on Gleason and prostate-specific antigen (PSA) can be determined by the
horizontal distance between the dot and the diagonal dashed line.
BIOPSY SETTING
In a study of 349 conservatively managed prostate cancer patients diagnosed using needle biopsy,
Clinical risk % (Gleason + PSA)
BIOPSY SETTING
Prolaris has been validated in 11 clinical studies with more than 5,000 patients.
Prolaris: Extensive Validation in both Bio psy and Radical Prostatectomy Settings
A study of 582 patients evaluated the prognostic utility of the Prolaris Score derived from biopsy specimens
Prolaris Score
in men who were treated by radical prostatectomy. Results from this study indicate that Prolaris can be
TM
was found to be the strongest independent predictor of prostate cancer-related death
and provided more information than either Gleason score or PSA.4
used at disease diagnosis to better define patient prognosis and enable more appropriate clinical care.5
10-year Estimated Biochemical Recurrence Progression-free Survival
10-year Estimated Prostate Cancer Death According to Prolaris (CCP) Score
>3 (n=16)
2 to ≤ 3 (n=50)
1 to ≤ 2 (n=114)
75
• Study demonstrates that
0 to ≤ 1 (n=133)
CCP score ≤ 0 (n=36)
Prolaris (CCP) Score pre-
50
dicts survival from prostate cancer.
25
Biochemical Recurrence
Progression-free Survival
Death from prostate cancer (%)
1.0
CCP score
100
0.8
•Prolaris (CCP) Score corre0.6
lates with the probability of
biochemical recurrence and
0.4
CCP score
was the strongest predictor
-2 to ≤ 0 (n=316)
of metastatic disease.
0 to ≤ 1 (n=185)
0.2
1 to ≤ 2 (n=67)
2 to ≤ 3 (n=14)
0
0
0
2
4
6
8
10
0
2
4
Time since diagnosis (years)
6
8
10
Years after surgery
A study of 141 prostate cancer patients treated with external beam radiation therapy (EBRT) with curative
Scatter Plot of Predicted 10-year Risk of Death From
Prostate Cancer for Combined Risk Score versus
Clinical Risk Score*
intent evaluated whether Prolaris test can be used as a prognostic indicator. The study showed that Prolaris
was significantly predictive of biochemical recurrence.6
100
Scatter Plot of Predicted 5-year Risk of BCR for
Combined Risk vs Clinical Risk*
50
Gleason score and PSA values improves
20
the 10-year survival prediction compared
to clinical parameters alone. 10
*Different Gleason score categories are shown by different colored dots
(blue, Gleason <7; orange, Gleason =7; red, Gleason >7). For any given
patient, the added contribution of the cell cycle progression (CCP) score
to the predicted risk based on Gleason and prostate-specific antigen (PSA)
can be determined by the horizontal distance between the dot and the
diagonal dashed line.
5
2
2
5
10
20
50
Combined risk % (CCP + Gleason + PSA)
100
Clinical risk % (Gleason + PSA + Percent
positive cores + Concurrent hormone use)
• Combining Prolaris (CCP) Score with
100
50
• Prolaris (CCP) Score provided prognostic
information that was not provided by
20
standard clinical parameters.
10
• Prolaris adds further risk stratification over and
5
above that provided by clinical risk parameters
alone.
2
1
Gleason <7
Gleason =7
Gleason >7
0.5
0.5
1
2
5
10
20
50 100
Combined risk %
(CCP + Gleason + PSA + Percent positive cores
+ Concurrent hormone use)
*Different Gleason score categories are shown by different colored dots (blue,
Gleason <7; orange, Gleason =7; red, Gleason >7). For any given patient, the
added contribution of the cell cycle progression (CCP) score to the predicted risk
based on Gleason and prostate-specific antigen (PSA) can be determined by the
horizontal distance between the dot and the diagonal dashed line.
BIOPSY SETTING
In a study of 349 conservatively managed prostate cancer patients diagnosed using needle biopsy,
Clinical risk % (Gleason + PSA)
BIOPSY SETTING
Prolaris has been validated in 11 clinical studies with more than 5,000 patients.
A study of 366 patients showed that in patients who had undergone radical prostatectomy, a high Prolaris
A prospective study evaluated the impact of the Prolaris testing on physician reccomendations for Prostate
Score was predictive of Biochemical Recurrence (BCR). The Prolaris Score was predictive of death after
Cancer Treatment. Clinicians ordering Prolaris test were asked how influential the test result was in making
disease progression and provided substantially more prognostic information than clinical variables alone.
therapeutic decisions.9
Prolaris was predictive of death after disease progression.7
150 Clinicians Completed Surveys on the Influence of the
Prolaris (CCP) Test in 305 Cases
10-year Estimated Biochemical Recurrence Rates
100
Patients with biochemical recurrence (%)
Change in Intended Therapeutic Options
(pre-CCP Test to Post - CCP Test)
Total (n=305)
Reduction
122 (40.0%)
No Change
107 (35.1%)
Increase
76 (24.9%)
CCP score
> 2 (n=6)
83.3%
1 to ≤ 2 (n=50)
80
> 0 to ≤ 1 (n=161)
≤ 0 (n=149)
• The proportion of patients
61.9%
60
who develop biochemical re44.5%
currence at different follow-up
40
times increases as the Prolaris
23.7%
(CCP) Score increases.
•In 65% of cases, there was a change recorded between the therapy initially planned and the therapy
actually selected (40% decrease and 25% increase).
•In 40% of cases, clinicians indicated they would reduce the intended therapeutic burden post Prolaris test.
•In 88% of cases, the influence of Prolaris on therapeutic treatment recommendations was moderate to
20
very high.
0
0
1
2
3
4
5
6
7
8
9
10
Based on the judgment of ordering physicians, the Prolaris Score adds meaningful
Time since surgery (years)
new information to risk assessment for localized prostate cancer patients.
A study of 413 patients concluded that Prolaris Score after radical prostatectomy provided independent
prognostic information beyond clinico-pathological parameters and could be useful in helping guide
decisions with respect to adjuvant treatment and in stratifying men for future adjuvant therapy studies.8
Prolaris adds Precisions to Conventional Risk Assessment
• With AUA (D'Amico) risk categories alone, all patients within one group (low, intermediate or high risk) are
assigned the same risk.
10-year Biochemical Progression-free Survival (Probability)
• The addition of Prolaris Score will help physicians: differentiate patients with similar AUA (D'Amico) risk
profiles better assess the near-term risk profile of patients make more confidente treatment decisions with
1.0
patients.
• Prolaris
0.8
(CCP)
Score
stratified
Prolaris® Further Stratifies Patients within Each AUA Biopsy Risk Category
patients in terms of risk of
ability to stratify risk was conserved
when separating out low risk from
0.4
intermediate/high
CCP score
0.2
< -1
2
risk
patients
(CAPRA-S score, 0 to 2) by clinical
-1 to -0.01
characteristics.
>0
0
100
biochemical recurrence. Prolaris‘s
0.6
4
6
Time (years)
8
10
3.9% risk of PCa death vs.
11% with AUA alone
50
AUA PCa Mortality Risk (%)
Biochemical Progression-free Survival (Probability)
PROSTATECTOMY SETTING
Prolaris significantly modifies treatment decisions in prostate cancer:
37% risk of PCa death vs.
11% with AUA alone
20
10
5
1.8% risk of PCa death
vs. 4.8% with AUA alone
2
6.7% risk of PCa death
vs. 4.8% with AUA alone
HIGH
INTERMEDIATE
LOW
1
1
2
5
10
20
AUA + Prolaris PCa Mortality Risk (%)
50
100
A study of 366 patients showed that in patients who had undergone radical prostatectomy, a high Prolaris
A prospective study evaluated the impact of the Prolaris testing on physician reccomendations for Prostate
Score was predictive of Biochemical Recurrence (BCR). The Prolaris Score was predictive of death after
Cancer Treatment. Clinicians ordering Prolaris test were asked how influential the test result was in making
disease progression and provided substantially more prognostic information than clinical variables alone.
therapeutic decisions.9
Prolaris was predictive of death after disease progression.7
150 Clinicians Completed Surveys on the Influence of the
Prolaris (CCP) Test in 305 Cases
10-year Estimated Biochemical Recurrence Rates
100
Patients with biochemical recurrence (%)
Change in Intended Therapeutic Options
(pre-CCP Test to Post - CCP Test)
Total (n=305)
Reduction
122 (40.0%)
No Change
107 (35.1%)
Increase
76 (24.9%)
CCP score
> 2 (n=6)
83.3%
1 to ≤ 2 (n=50)
80
> 0 to ≤ 1 (n=161)
≤ 0 (n=149)
• The proportion of patients
61.9%
60
who develop biochemical re44.5%
currence at different follow-up
40
times increases as the Prolaris
23.7%
(CCP) Score increases.
•In 65% of cases, there was a change recorded between the therapy initially planned and the therapy
actually selected (40% decrease and 25% increase).
•In 40% of cases, clinicians indicated they would reduce the intended therapeutic burden post Prolaris test.
•In 88% of cases, the influence of Prolaris on therapeutic treatment recommendations was moderate to
20
very high.
0
0
1
2
3
4
5
6
7
8
9
10
Based on the judgment of ordering physicians, the Prolaris Score adds meaningful
Time since surgery (years)
new information to risk assessment for localized prostate cancer patients.
A study of 413 patients concluded that Prolaris Score after radical prostatectomy provided independent
prognostic information beyond clinico-pathological parameters and could be useful in helping guide
decisions with respect to adjuvant treatment and in stratifying men for future adjuvant therapy studies.8
Prolaris adds Precisions to Conventional Risk Assessment
• With AUA (D'Amico) risk categories alone, all patients within one group (low, intermediate or high risk) are
assigned the same risk.
10-year Biochemical Progression-free Survival (Probability)
• The addition of Prolaris Score will help physicians: differentiate patients with similar AUA (D'Amico) risk
profiles better assess the near-term risk profile of patients make more confidente treatment decisions with
1.0
patients.
• Prolaris
0.8
(CCP)
Score
stratified
Prolaris® Further Stratifies Patients within Each AUA Biopsy Risk Category
patients in terms of risk of
ability to stratify risk was conserved
when separating out low risk from
0.4
intermediate/high
CCP score
0.2
< -1
2
risk
patients
(CAPRA-S score, 0 to 2) by clinical
-1 to -0.01
characteristics.
>0
0
100
biochemical recurrence. Prolaris‘s
0.6
4
6
Time (years)
8
10
3.9% risk of PCa death vs.
11% with AUA alone
50
AUA PCa Mortality Risk (%)
Biochemical Progression-free Survival (Probability)
PROSTATECTOMY SETTING
Prolaris significantly modifies treatment decisions in prostate cancer:
37% risk of PCa death vs.
11% with AUA alone
20
10
5
1.8% risk of PCa death
vs. 4.8% with AUA alone
2
6.7% risk of PCa death
vs. 4.8% with AUA alone
HIGH
INTERMEDIATE
LOW
1
1
2
5
10
20
AUA + Prolaris PCa Mortality Risk (%)
50
100
Prolaris® Benefits:
Prolaris® addresses a currently unmet need in prostate cancer by providing the clinician with
direct information about prostate tumor aggressiveness that may be used to make more
confident management decisions.
1. For example, at the time of diagnosis, a low Prolaris ScoreTM in the context of low-risk clinico-pathologic
features may more accurately identify patients who are the best candidates for active surveillance.
2. Alternatively, a high Prolaris Score in patients with an intermediate risk profile may alter the management
with additional staging and more aggressive (combination) therapy.
Prolaris also provides information that may be used to guide the extent of adjuvant treatment
after primary therapy.
3. For example, a high Prolaris Score in the context of high-risk pathologic findings after radical prostatectomy
may help identify patients who are appropriate candidates for adjuvant radiation.
“It seems certain that, particularly in men in whom the management approach is uncertain…there is a lot
of information in this test to help you decide whether you need more aggressive therapy or can manage
them more conservatively.”
Prof. Jack Cuzick, Queen Mary, University of London, UK
References:
PROL_MDBRO_06_14_ENV2
Not for distribution in USA.
1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–917.
2. Cancer Stats Worldwide Report jointly prepared by Cancer Research UK and the International Agency for Research on Cancer (IARC) January 2014
http://publications.cancerresearchuk.org/downloads/Product/CS_REPORT_WORLD.pdf
3. EAU Guidelines on Prostate Cancer, Update March 2013 http://www.uroweb.org/gls/pdf/09_Prostate_Cancer_LR.pdf
4. Cuzick J et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. British
Journal of Cancer 2012; 106(6): 1095-1099.
5. Bishoff J et al. Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. The Journal of Urology,
Published online 10 February 2014.
6. Freedland SJ et al. Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat
Oncol Biol Phys 2013; 86: 848–53.
7. Cuzick J et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes for in patients with prostate cancer: a
retrospective study. Lancet Oncol 2011; 12: 245–55.
8. Cooperberg MR et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol
2013;31: 1428–34.
9. Crawford D et al. Cell cycle progression score and treatment decisions in prostate cancer: results from an ongoing registry. Curr Med Res Opin 2014; 1–7
Published Online 13 March 2014.
A prognostic medicine product for prostate cancer.
Prolaris® testing assesses prostate cancer aggressiveness in conjunction with other clinical parameters. Prolaris® measures
the expression level of genes involved with cell cycle progression (CCP) in tumor specimens to predict disease outcome.
Myriad Genetics GmbH
Leutschenbachstrasse 95
8050 Zurich
Switzerland
www.myriadgenetics.eu
Myriad, the Myriad logo, Prolaris and the Prolaris logo are either trademarks or registered trademarks of Myriad Genetics, Inc.,
in the United States and other jurisdictions.
©2014, Myriad Genetics, GmbH. Not for distribution in USA.