Debate: Genetics and Genomics should be used ONLY for re-biopsy

Transcription

1 Debate: Genetics and Genomics should be used ONLY for re-biopsy Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC Dept of Urologic Sciences Director of Development and Supportive Care, Vancouver Prostate Centre Vancouver, BC, Canada

2 Financial and Other Disclosures Off-label use of drugs, devices, or other agents: None Data from IRB-approved human research is presented I have the following financial interests or relationships to disclose: No financial relationships Disclosure code N

3 The Basics: what are we trained to think & do? age PSA family history Free:total PSA ratio ethnicity DRE LUTS What is my patient s risk for having SIGNIFICANT prostate cancer?

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5 A Confusing Pathway towards diagnosis PSA plus derivatives (free, PSAD) mp-mri, PCA3, phi, 4K, SelectMDx, ConfirmMDx, TMPRSS2:ERG fusion Prostarix microrna, cell-free DNA And more in the pipeline!!

6 Dilemma: The False-Negative Biopsy Out of 1.3 million men who undergo a prostate biopsy, 241,000 are diagnosed with cancer. However up to 1 in 4 men are misdiagnosed with a False Negative result. 19 million annual PSA screenings 4.7 million abnormal PSA test results >1.3 million prostate biopsy procedures 241,000 diagnosed with PCa 28,000 deaths >1,000,000 Patients with negative biopsy result up to 25% with false-negative results Fear of occult cancer leads to a high rate of repeat biopsies. Aubry W et al: Budget Impact Model: Epigenetic Assay Can Help Avoid Unnecessary Repeated Prostate Biopsies and Reduce Healthcare Spending. American Health Drug and Benefits (1): 15-24

7 Negative First Biopsy: 43% have 1st repeat biopsy 44% have a 2nd repeat biopsy 43% have a 3rd repeat biopsy US: Approximately 700,000 repeat biopsies annually. The Fear of Undetected Cancer Leads to utilization of new markers prior to first biopsy in all men. I propose that NOT all first biopsy cases have adjunctive testing; reserve for those with negative first and ongoing concern 1. Welch HG et al: Detection of Prostate Cancer via Biopsy in the Medicare SEER Population During the PSA Era. J Natl Cancer Inst 2007;99: Pinsky PF et al: Repeat Prostate Biopsy in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. BJU International 99, no. 4 (April 2007):

8 Willet Whitmore (circa 1975) The current state of prostate cancer may not be good medicine but it sure is good business. There are more people making a living from prostate cancer than there are dying from it.

9 Value: at what dollar cost? Robot: $2500 to 21,500 IMRT: $17,970 Brachy: $7,866 Proton: $68,000 HIFU: $22,000 + travel Provenge: $93,000 CAR-T: $373,000 one time Abiraterone (Zytiga): $41,362/yr Enzalutamide (Xtandi): $29,200/yr Pembrolizumab: $156,000/yr Cabazitaxel: $10,000/cycle Radium 223 (Xofigo): $12,000/cycle Zoledronate: $1,250/dose Denosumab: $24,000/year

10 What is Value? a fair return or equivalent - in goods, services, or money for something exchanged Nothing is intrinsically valuable; the value of everything is attributed to it, assigned to it from outside the thing itself, by people. John Barth Price is what you pay. Value is what you get. Webster s Warren Buffett

11 What is Value in Healthcare? should be a significant driver of healthcare performance improvements should NOT be an abstract ideal should NOT be a code word for cost reduction

12 What is Value in Healthcare? Our goal must be high value in a patient-centred model, to unite the interests of all involved in healthcare. Improved value will benefit pts, providers, payers and suppliers, and will contribute to the sustainability of the system.

13 The Value Ratio Value = health outcomes achieved dollars spent

14 The value ratio: denominator Value = health outcomes achieved dollars spent Cost is not a single test, therapy or service; must reflect the full cycle of care for the medical condition Cannot costs (eg avoid a genomic classifier) to value without paying attention to the outcomes ( false savings )

15 The value ratio: nominator Value = health outcomes achieved dollars spent Outcomes are multidimensional, condition specific and no single outcome (eg yield of high grade cancers) captures results of care

16 Principles of measuring outcomes in the value ratio measurement of initial conditions to allow for risk adjustment (eg prevalence of aggressive cancer in population) track near-term and long-term outcomes and costs longitudinally eg. occurrences of treatment-induced illnesses, need for secondary treatment Other measures: number/quality of life years saved impact on institutional budget and other hospital programs

17 New kids in town - a medical syndrome

18 4K SelectMDx Mp-MRI

19 The Cost-Effectiveness Plane New test more costly Pca diagnostics EXISTING test dominates New test more effective but more costly New test less effective New test more effective New test less effective but less costly NEW test dominates New test less costly

20 Our Goal, after a Negative initial biopsy: Decrease the number of repeat biopsies in men, especially those with no cancer, or low risk cancers Increase yield of aggressive cancer Minimize medical, personal and societal risks and costs by reserving these tests for re-biopsy. HOW??

21 Cheap Option: Risk Calculator / Nomogram J Urol, 170:1184, 2003

22 Germ Line Studies? Test for BRCA ½ when personal history of Gleason 7 at any age, with 1 close blood relative with ovarian Ca at any age or breast cancer 50 yrs or 2 relatives with bereast, pancreatic or prostate cancer at any age Screen at age 45 for BRCA 2 (can consider BRCA 1) NCCN guidelines:

23 mp-mri prior to initial Biopsy Using mp-mri might allow 27% of patients to avoid a primary biopsy and diagnose 5% fewer clinically insignificant cancers Lancet PROMIS study

24 mpmri outperforms PCA3 and PHI to predict cancer in men with negative biopsies 170 prospective patients with negative biopsy mpmri, PHI and PCA3 prior to standard repeat biopsy (blinded to mpmri) mpmri: AUC 0.936; only significant independent predictor of PCa Conclusion: Consider mpmri as valid tool for avoiding unnecessary repeat biopsies Porpiglia et al., J Urol, 2014

25 4Kscore Test Strong Discrimination for High-Grade Cancer Based on MSKCC Prospective, 26 Center US Clinical Trial Oct Apr ,012 Patients, No PSA, Age, DRE, Prior Bx Exclusion 43% Biopsy reduction at 9% risk cut off

26 SelectMDx urine biomarker May be a good triage test for MRI AUC 0.68 AUC AUC % NPV for high grade prostate cancer Avoiding unnecessary biopsies 53% 36% PCA3 SelectM Dx PCA3 SelectMDx

27 1 st biopsy negative Costs per test PSA Risk Calculator mp-mri 4K PCA3 SelectMDx ConfirmMDx $30 $0 $1,000 $700 $300 $500 $3,300 $1,030 $5,300 Re-Biopsy $600

28 Q: What is your value threshold for adjunctive testing prior to First and/or Re-biopsy in men with varying levels of suspicion of significant cancer? Decreased # biopsies Increased yield of significant Ca $$$$ Bx complications

29 Beware of being squeezed by marketing forces and jumping on the bandwagon before the cost effectiveness of each test has been determined

30 Thankyou