Adam Raben M.D. Helen F Graham Cancer Center

Transcription

1 Adam Raben M.D. Helen F Graham Cancer Center

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3 Is the biopsy sample representative of the extent of the disease in your patient with clinically low-risk prostate cancer?

4 BIOPSY RP registry (n=8095) 3+3=6 (GG1) (n=6360) 3+3=6 74.4% PROSTATECTOMY 3+4=7 > % 3.3% Nonorgan confined 6.1% In a substantial number of cases, Biopsy Gleason differs from pathological Gleason Biopsy Gleason Score may not accurately reflect the true nature of the tumor 3+4=7 (GG2) (n=1735 NCCN Fav. Intermed. ) 22.3% 63.6% 12.3% 17.4% Undermines confidence in decision making Genomic testing gives you critical information to help guide management decisions Gearman et al., J Urol 2017

5 Michael 68 year old African American, healthy man George 65 year old Caucasian American, healthy man Unit Value Gleason 3+3=6 PSA 5.4 ng/ml PSAD.18 ng/ml/cc Cores Positive 2/12, <50% Positive Volume 30cc NCCN Risk Category Low Stage ct1c Patient names, images, and pathology photos are illustrative. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

6 Many patients with low-risk cancer are unnecessarily treated 1,2 Some patients who have unrecognized high-risk disease are undertreated and may miss a chance for a cure 3 Currently available clinical risk factors have limitations 4 1. Hamdy et al. N Engl J Med. 2016; 2. Cooperberg, Carroll. JAMA 2015; 3. Yamamoto et al. J Urol. 2016; 4. Brand et al. Urol

7 WHAT does the GPS assay report? AP Adverse Pathology at RP 1-2 METS DEATH At 10 years after RP 3 1. Klein et al. Eur Urol. 2014; 2. Knezevic et al. BMC Genomics. 2013; 3. Van Den Eeden et al. Eur Urol AP- Adverse Pathology, RP- radical prostatectomy

8 NCCN Guidelines Version Prostate Cancer Page 9 of NCCN Guidelines I Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for Prostate Cancer V National Comprehensive Cancer Network, Inc Assessed February 20, To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

9 Does my patient have Occult High-risk Disease?

10 Adverse Pathology IS YOUR KEY DECISION POINT Adverse Pathology is the likelihood your patient is harboring aggressive disease (dominant pattern 4, any pattern 5 or pt3) 1 and is pivotal in the risk assessment when selecting a management decision in clinically low-risk prostate cancer patients Cullen et al. Eur Urol. 2015

11 Development Validation Utility Study 1 (n = 441) 1 Cleveland Clinic (Prostatectomy study) Study 2 (n = 167) 2 Cleveland Clinic (Biopsy study) Bx GS 6 70% Bx GS 7 25% L 57%, Int 43% Study 1 (n = 395) 1 University of California, San Francisco Study 2 (n = 402) 3 VL 11%, L 54%, Int 35% Center for Prostate Disease Research (VA) Study 3 (n = 259) 6 Kaiser Northern California VL 9%, L 48%, Int 41% VL 3%, L 21%, Int 67% Study 1 (n = 158) 4 Columbia University VL 22%, L 45%, Int 33% Study 2 (n = 124) 5 University of California Davis VL 42%, L 40%, Int 17% Study 3 (n = 258) 7 22 US Community Practice Sites VL 39%, L 28%, Int 34% Study 4 (n = 80) 8 Excellus BCBS Payor Utility study Study 5 (n = 375) 9 OPTUM Payer Utility Study 1. Klein et al. Eur Urol. 2014; 2. Knezevic et al. BMC Genomics. 2013; 3. Cullen et al. Eur Urol. 2015; 4. Badani et al. Urol Pract. 2015; 5. Dall Era et al. Urol Pract. 2015; 6. Van Den Eeden et al. J Urol Abstract MP20-05; 7. Eure et al. Urology Albala et al., Rev in Urology 2016; 9 Canfield et al., Rev in Urology 2017

12 727 candidate genes 374 genes Primary Gleason Sample genes genes 367 genes Highest Gleason Sample Knezevic et al. BMC Genomics. 2013; Klein et al. Eur Urol

13 Development Studies The expression of 727 cancer specific genes was quantified independently in tissue from the primary and highest Gleason patterns in prostatectomy specimens Only genes predictive of clinical recurrence in both specimens were selected for further development in biopsy specimens Knezevic et al. BMC Genomics. 2013; Klein et al. Eur Urol

14 Androgen Signaling Cellular Organization Stromal Response Cellular Proliferation Reference AZGP1 FAM13C KLK2 SRD5A2 FLNC GSN GSTM2 TPM2 BGN COL1A1 SFRP4 TPX2 ARF1 ATP5E CLTC GPS1 PGK1 Associated with a better outcome Associated with a worse outcome

15 Intermediate Low Very Low Are these the ideal patients for Radical Prostatectomy? Are these the ideal patients for Active Surveillance? Brand et al. Urology Katz et al. AUA Annual Meeting, May 2015.

16 NCCN -based Clinical Risk Assessment VERY LOW LOW INTERMEDIATE 30% 39% 32% GPS Characterizes a patient s tumor biology and refines the population-based clinical risk with a more personalized risk assessment n = 3816 GPS Individualized Biologic and Clinical Risk Assessment VERY LOW LOW INTERMEDIATE 41% 26% 32% 48% of NCCN low-risk patients had a different biological risk group than their NCCN risk group (consistent results with published validation cohort) Katz et al. AUA Annual Meeting, Klein et al. Eur Urol, NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Percentages do not calculate to 100 due to rounding

17 6184 All Eligible patients Prostate cancer death (PCD) 64 PCD 195 Non-PCD 259 Final Evaluation Sample 79 Mets Metastasis 180 Non-Mets Van Den Eeden et al. Eur Urol BCR Biochemical Recurrence NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

18 10-year Risk of Metastasis 10-year Risk of Death Variable HR HR 95% CI P-value GPS per 20 Units 2.34 (1.42, 3.86) <.001 Variable HR HR 95% CI P-value GPS per 20 Units 2.69 (1.50, 4.82) <.001 Van Den Eeden et al. Eur Urol Results are from a multivariable model adjusting for NCCN risk group HR Hazard Ratio

19 100% 80% 60% 40% 20% 0% Proportion of AS Persistence at 6 and 12- Month Follow-up 1 60% 56% No GPS or MRI (n = 7446) 89% 84% GPS (n = 300) 30% Absolute Increase in Active Surveillance Among GPS Tested * 6-mo 12-mo P< Canfield, et. al. Rev Urol *Adjusted for demographic and background characteristics. AS-Active Surveillance

20 mpmri is a breakthrough improvement and has the potential to improve both screening and management of prostate cancer More likely to diagnose significant prostate cancer 1 However; significant limitations exist, including but not limited to: Poor sensitivity for extraprostatic extension 2 Potential for interobserver/intraobserver variability in interpretation 3 Marginal positive predictive value in some studies 4 Potentially underestimates tumor volume 1 75% MRI misses up to 75% of small (< 0.5 cc ) Gleason 4+3 tumors 5 1. Weinreb JC et al. Eur Urol. 2016; 2. de Rooij et al. Eur Urol. 2016; 3. Muller et al. Radiology. 2015; 4. Thompson et al. J Urol. 2015; 5. Vargas et al. Eur Radiol

21 Michael, 68 Healthy man George, 65 Healthy man Unit Value Gleason 3+3=6 PSA 5.4 ng/ml PSAD.18 ng/ml/cc Cores Positive 2/12, <50% Positive Volume 30cc NCCN Risk Category Low Stage ct1c? Patient names, images, and pathology photos are illustrative. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

22 Michael, 68 Top-line results integrate clinical variables into a single composite risk estimate T1 c Baseline clinical data highlighted for ease of reference during discussion with your patient NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

23 Michael, 68 Healthy man Risk for specific outcomes clearly articulated on a slider bar NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

24 Michael, 68 Healthy man

25 George, 65 NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

26 Michael George Gleason 3+3=6 (GG1) PSA of 5.4 ng/ml PSAD of 0.18 ng/ml/cc Volume of 30 cc 2/12 Cores Positive ct1c NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

27 Oncotype DX GPS Assay is supported by numerous studies 1-8 The Oncotype DX GPS test helps predict short- AND long-term risks Adverse Pathology at the time of diagnosis 2,3 Metastasis within 10 years after RP 6 Prostate cancer death within 10 years after RP 6 Medicare covers the GPS assay for patients with NCCN very low, lowrisk and favorable intermediate prostate cancer patients Private coverage varies by plan Genomic Access Program was created to help your eligible patients determine payment options for our tests, including Oncotype DX GPS 1. Knezevic et al. BMC Genomics. 2013; 2. Klein et al. Eur Urol. 2014; 3. Cullen et al. Eur Urol. 2015; 4. Badani et al. Urol Pract. 2015; 5. Dall Era et al. Urol Pract. 2015; 6. Van Den Eeden et al. J Urol. 2017; 7. Eure et al. Urology Genomic Health, Inc. Data on file. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.