THE CCP SCORE: A NOVEL GENETIC TEST FOR PROSTATE CANCERMichael Brawer,1 Jack Cuzick,2 Matt hew Cooperberg,3 Greg Swanson,4 Stephen Freedland,1 Julia Reid,5 Gabrielle Fisher,2 Jerry Lanchbury,5 Alexander Guti n,5 Steven Stone,5 Peter Carroll3

1)Myriad Geneti c Laboratories, Inc., Salt Lake City, UT, USA 2)Wolfson Insti tute of Preventi ve Medicine, London, United Kingdom 3)UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA, 4)University of Texas Health Science Center, San Antonio, TX, USA 5)Myriad Geneti cs, Inc., Salt Lake City, UT, USA

Table 1. Summary of Prostate Cancer Studies

Study Title Sample Type Number of Pati ents (Events) Endpoint Reference

TURPConservati vely Managed TURP 337

(76, 23%)Death from

prostate cancer

Cuzick et al. Lancet Oncology 2011;12(3):245-55.

Needle BiopsyConservati vely Managed Biopsy 349

(90, 26%)Death from

prostate cancer

Cuzick et al. Briti sh Journal of Cancer 2012;106:1095-99.

Radical Prostatectomy (RP) 1

Radical Prostatectomy

353 (132, 37%)

Biochemical recurrence (BCR)

Cuzick et al. Lancet Oncology 2011;12(3):245-55.

RP 2 Radical Prostatectomy

413 (82, 20%) BCR

Cooperberg et al. Journal of Clinical Oncology 2013;31:1428-34.

External Beam Radiati on Therapy (EBRT) Biopsy 141

(19, 13%) BCR*Freedland et al. Int J Radiat Oncol Biol Phys 2013;86(5):848-53.

Biopsy - RP 1 Simulated Biopsy

283 (48, 17%) BCR Bishoff et al.

2013 in preparati on

Biopsy - RP 2 Biopsy 176 (83, 47%) BCR Bishoff et al.

2013 in preparati on

Biopsy -RP 3 Biopsy 123 (35, 28%) BCR Bishoff et al.

2013 in preparati on

* Censored at 5 years.

Table 2. CCP Score in Univariate Cox PH Models

Study TitleCCP score log PSA Gleason Score

Hazard rati o95% CI p-value p-value p-value

TURP - Conservati vely managed 2.9 (2.4, 3.6) <10-21 <10-13 <10-18

Needle Biopsy - Conservati vely managed 2.0 (1.6, 2.5) <10-9 <10-4 <10-7

RP 1 2.0 (1.6, 2.4) <10-8 <10-17 <10-9

RP 2 2.1 (1.6, 2.9) <10-5 0.0035 <10-5

EBRT 2.6 (1.4, 4.6) 0.0017 <10-3 0.051Biopsy - RP 1 2.1 (1.5, 2.8) <10-4 <10-4 <10-3

Biopsy - RP 2 1.3 (1.0, 1.7) 0.027 0.012 0.34Biopsy - RP 3 1.9 (1.2, 2.8) 0.0028 <10-5 <10-3

Table 3. CCP Score in Multi variate Cox PH Models

Study TitleMulti variate model (may include additi onal clinical covariates)

Hazard rati o95% CI

CCP scorep-value

log PSAp-value

Gleason Score p-value

TURP - Conservati vely managed 2.6 (1.9, 3.4) <10-10 <10-7 0.028Needle Biopsy - Conservati vely managed 1.7 (1.3, 2.1) <10-4 0.017 0.0022RP 1 1.7 (1.4, 2.2) <10-5 <10-8 0.015RP 2 2.0 (1.4, 2.8) <10-4 0.12 0.17EBRT 2.1 (1.0, 4.2) 0.035 0.087 0.20Biopsy - RP 1 1.7 (1.2, 2.3) 0.0033 0.0029 0.038Biopsy - RP 2 1.3 (1.0, 1.7) 0.031 0.029 0.65Biopsy - RP 3 1.6 (1.0, 2.4) 0.041 <10-3 0.14

BACKGROUND• Prostate cancer has a highly variable natural history and

accurately assessing the tumor’s aggressiveness based on clinical and pathologic features is challenging.

• Novel prognosti c markers are needed to more precisely guide therapeuti c decisions.

• The CCP signature test (Prolaris®) measures the acti vity of cell cycle progression genes in prostate cancer ti ssue.

• Prolaris has now been tested in eight cohorts.

METHODS• All studies were retrospecti ve.• Formalin fi xed prostate ti ssue from men with

adenocarcinoma were analyzed.• The CCP score is calculated by measuring the

average RNA expression of 31 cell cycle progression genes normalized by the average expression of 15 housekeeping genes as quanti tated by RT-PCR.

RESULTS• The CCP signature test was a highly signifi cant

predictor of outcome in all eight studies.• The CCP score was the dominant or co-dominant

predictor in multi variate analysis.• In all eight of the multi variate studies, the hazard

rati os (HRs) per unit of change in the Prolaris score were remarkably similar, ranging from 1.3 to 2.6.

• These HRs indicate that the eff ect size for the CCP score is robust in varying clinical setti ngs.

Figure 1. Predicted Risk in Conservati vely Managed CasesConservati vely Managed Cases

0 20 40 60 80 100

0

20

40

60

80

100

Glea

son

Risk

%

CCP Score + Gleason Risk %

Figure 2. Predicted Risk in Radical Prostatectomy Cases

0 20 40 60 80 100

0

20

40

60

80

100

Glea

son

Risk

%

CCP Score + Gleason Risk %

Radical Prostatectomy CasesFigure 3. Predicted Risk in Biopsies before

Radical Prostatectomy or EBRT

0 20 40 60 80 100

0

20

40

60

80

100

Glea

son

Risk

%

CCP Score + Gleason Risk %

Radical Prostatectomy or EBRT

CONCLUSIONS• The CCP signature test predicts prostate cancer

outcome in multi ple pati ent cohorts and in diverse clinical setti ngs.

• The CCP signature test provides independent informati on beyond clinicopathologic variables.

• The CCP signature test helps to further diff erenti ate aggressive prostate cancer from indolent cancer.

Presented at AUA Northeastern Sectional Meeting - October 31, 2013