Using Prolaris to help determine the risk of prostate cancer progression

1. An experience with Prolaris in
the decision making for men
diagnosed with prostate cancer
Marc Laniado MD FEBU FRCS(Urol)

2. Would what
would you do
with this man?
Age 55 years
PSA 6
14% free PSA,
clinical stage Stage T2
No Family history
No comorbidity

3. 55 year old, PSA 6
mpMRI
T2
T2
DCE
ADC

4. 55 year old, PSA 6,
Gleason Score 3+3=6
mpMRI
T2
T2
DCE
ADC

5. Years
a'er
diagnosis
Dead
from
prostate
cancer
Dead
from
other
causes
4%
chance
of
dying
a'er
10
y
for
low
risk
disease
in
PSA
era
in
65
year
old
Contains
Gleason
paDern
3
only
1
2
3
4
5

6. Low risk cancers are about
50% of new cancer diagnoses
High
Intermediate/high
Intermediate
Low

7. Treatment
OpIons
are
Broad
&
Unclear
?

8. If
you
don’t
know
your
risk,
you
don’t
know
what
decision
to
take

9. Urgent
Need
for
Precision
Medicine
“linkage of molecular data to
health outcomes in order to
allow a more precise clinical
decision making that is
tailored to individual patients”
Institute of Medicine, 2011

10. PROLARIS:
cell cycle
progression
Score
ratio of
proliferation
gene to normal
gene activity

11. Appearances similar outside
but different inside
Basic
model
Luxury
interior
Sports
engine

12. Appearances similar outside
but different inside
Gleason score 6
Gleason score 6
Gleason score 6
Increasing ratio of proliferation gene activity

13. AUA risk
Low
Intermediate
High

14. AUA risk V Prolaris
Low
Intermediate
High

15. Prolaris separates low risk
into trustworthy low risk
‘Low risk’ - some are
high risk
‘Intermediate’:
some are actually low
risk

16. 55 year old, PSA 6, Gleason
Score 3+3=6
mpMRI
T2
T2
DCE
ADC

17. My
paIent
read
this
book….

18. He wanted precision diagnostics

19. His Prolaris score was -2.1
Continued with active monitoring

20. 10 year prostate cancer specific
mortality rate was reduced to 1%
Continued with active monitoring

21. 66 year old man with
previous -ve TRUS biopsy

22. 66 years old, PSA 7 ng/ml,
T2A
Continued with active monitoring

23. Prolaris needs to be better
than multivariable prediction
• Kattan Nomogam
• CAPRA score
• SWOP Prostate Cancer Risk Calculator

24. CAncer of the Prostate Risk
Assessment - CAPRA
Variable Level Points
Age at diagnosis Under 50 0
50 or older 1
PSA at diagnosis less than or = 6 0
between 6.1-10 1
between 10.1-20 2
between 20.1-30 3
more than 30 4
Bx Gleason Score no pattern 4 or 5 0
secondary 4 or 5 1
primary 4 or 5 3
Clinical (T) stage T1 or T2 0
T3a 1
% positive Bx cores less than 34% 0
34% or more 1
Cancer of the Prostate
Risk Assessment
(CAPRA)
• CAPRA 0-2
= Low Risk
• CAPRA 3-5
= Intermediate Risk
• CAPRA 6-10
= High Risk

25. Prolaris adds precision to
CAPRA score
CAPRA < 3

26. Prolaris score distribution results in more
than half the patients being recategorised
AUA Risk
Classification
Considerably
Less
Aggressive
Less
Aggressive
Consistent
More
Aggressive
Considerably
More
Aggressive
Totals
Low 2% 24% 47% 23% 23% 583
Intermediate 2% 26% 45% 23% 4% 740
High 4% 25% 38% 24% 9% 281
Totals 3% 25% 45% 23% 4% 1604

27. Prolaris changes the decision
to treat or not treat in 2/3 cases

28. 72 years, PSA 8, pT2, Gleason pattern 4
cancer at the apex - adjuvant radiotherapy

29. CAncer of the Prostate Risk
Assessment Post-Surgical CAPRA-S
Variable Level Points
Pre-op PSA 0.00 to 6.00 0
6.01 to 10.00 1
10.01 to 20.00 2
> 20.00 3
Path. Gleason < 3 + 3 = 6 0
3 + 4 = 7 1
4 + 3 = 7 2
> 4 + 4 = 8 3
Margins Negative 0
Positive 2
ECE No 0
Yes 2
SVI No 0
Yes 2
LNI No 0
Yes 1
• CAPRA-S 0-2
low risk
• CAPRA-S 3-5
Intermediate risk
• CAPRA-S >5
High risk

30. CAncer of the Prostate Risk
Assessment Post-Surgical CAPRA-S
Variable Level Points
Pre-op PSA 0.00 to 6.00 0
6.01 to 10.00 1
10.01 to 20.00 2
> 20.00 3
Path. Gleason < 3 + 3 = 6 0
3 + 4 = 7 1
4 + 3 = 7 2
> 4 + 4 = 8 3
Margins Negative 0
Positive 2
ECE No 0
Yes 2
SVI No 0
Yes 2
LNI No 0
Yes 1
• CAPRA-S 0-2
low risk
• CAPRA-S 3-5
Intermediate risk
• CAPRA-S >5
High risk

31. Postsurgery Recurrence
Risk is More Predictable
Low risk (CAPRA-S 0-2) Intermediate/high risk (CAPRA-S > 3)
CCP < -1
CCP -1 to 0
CCP > 0

32. Post robotic prostatectomy -
15% chance of recurrence
Chose no adjuvant radiotherapy
&
Very Happy!

33. The
Prolaris
Test
adds
value
over
the
CAPRA-­‐S
score
alone
33
Cooperberg JCO 2013Decision Curve Analysis,

34. Points to consider on biomarkers
• Skeptic: “Can’t be sure that this test will be 100%
accurate so why use and pay for it?”
• Response: Incremental steps that make us better
not perfect decision makers - currently poor
discrimination anyway
• 1st generation assays are 1st generation!!
• Add to, but do not replace existing tests

35. Place
of
Prolaris
in
OpImal
Early
Prostate
Cancer
Pathway?
Prostate
Cancer
Risk
calculator
Any
Ca
>20%
risk
high
grade
PCa>4%
risk
MulIparametric
MRI
Only
3%
chance
of
prostate
Ca
-­‐
monitor
outside
hospital
MRI-­‐targetd
prostate
biopsies
Low
risk
localised
High
risk
localised
prostatectomyAS
mpMRI-­‐ve
&
PSA
<15
Brachy
Focal
PSA>15
or
mpMRI+