Impact of a genomic classifier of metastatic risk on postoperative treatment recommendations for prostate cancer patients: a report from the DECIDE study group

Ketan Badani, Darby J S Thompson, Christine Buerki, Elai Davicioni, Jill Garrison, Mercedeh Ghadessi, Anirban P Mitra, Penelope J Wood, John Hornberger, Ketan Badani, Darby J S Thompson, Christine Buerki, Elai Davicioni, Jill Garrison, Mercedeh Ghadessi, Anirban P Mitra, Penelope J Wood, John Hornberger

Abstract

Background: Only a minority of prostate cancer patients with adverse pathology and biochemical recurrence (BCR) post radical prostatectomy (RP) experience metastasis and die from prostate cancer. Improved risk prediction models using genomic information may enable clinicians to better weigh the risk of metastasis and the morbidity and costs of treatment in a clinically heterogeneous population.

Purpose: We present a clinical utility study that evaluates the influence on urologist treatment recommendations for patients at risk of metastasis using a genomic-based prediction model (DecipherTM).

Methods: A prospective, pre-post design was used to assess urologist treatment recommendations following RP in both the adjuvant (without any evidence of PSA rise) and salvage (BCR) settings. Urologists were presented de-identified pathology reports and genomic classifier (GC) test results for 24 patients from a previously conducted GC validation study in high-risk post-RP men. Participants were fellowship trained, high-volume urologic oncologists (n=21) from 18 US institutions. Treatment recommendations for secondary therapy were made based solely on clinical information (pre-GC) and then with genomic biomarker information (post-GC). This study was approved by an independent IRB.

Results: Treatment recommendations changed from pre-GC to post-GC in 43% of adjuvant, and in 53% of salvage setting case evaluations. In the adjuvant setting, urologists changed their treatment recommendations from treatment (i.e. radiation and/or hormones) to close observation post-GC in 27% of cases. For cases with low GC risk (more than 3% risk of metastasis), observation was recommended for 79% of the case evaluations post-GC. Consistent trends were observed in the salvage setting.

Conclusion: These results indicate that urologists across a range of practice settings are likely to change treatment decisions when presented with genomic biomarker information following RP. Implementation of genomic risk stratification into routine clinical practice may better direct treatment decision-making post-RP.

Conflict of interest statement

This study was supported by GenomeDx Biosciences. 4 co-authors are employees of the sponsor.

Figures

Figure 1. Breakdown of treatment recommendations pre-GC…
Figure 1. Breakdown of treatment recommendations pre-GC and post-GC for low and high GC risk groups in the adjuvant setting.
Figure 2. Proportion of recommendations for treatment…
Figure 2. Proportion of recommendations for treatment for the indicated values of clinical variables (e.g. Presence/Absence) Pre-GC and the resulting proportion recommended for treatment post-GC in high and low GC risk groups in the adjuvant setting.

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: a cancer journal for clinicians. 2013;63(63):11–30.
    1. Marciscano AE, Hardee ME, Sanfilippo N. Management of high-risk localized prostate cancer. Advances in urology. 2012;2012 641689.
    1. Swanson GP, Riggs M, Hermans M. Pathologic findings at radical prostatectomy: risk factors for failure and death. Urologic oncology. 2007;25(25):110–114.
    1. NCCN. NCCN Clinical Guidelines in Oncology (NCCN Guideline) Prostate Cancer. 2013 Version 1.
    1. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA : the journal of the American Medical Association. 1999;281(281):1591–1597.
    1. Boorjian SA, Thompson RH, Tollefson MK, Rangel LJ, Bergstralh EJ, Blute ML, Karnes RJ. Long-term risk of clinical progression after biochemical recurrence following radical prostatectomy: the impact of time from surgery to recurrence. European urology. 2011;59(59):893–899.
    1. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW. Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007;25(25):1765–1771.
    1. Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset J-F, van Velthoven R, Maréchal J-M, Scalliet P, Haustermans K, Piérart M. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911) The Lancet. 2005;366(366):572–578.
    1. Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, Messing E, Forman J, Chin J, Swanson G, Canby-Hagino E, Crawford ED. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. The Journal of urology. 2009;181(181):956–962.
    1. Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Storkel S, Willich N, Semjonow A, Souchon R, Stockle M, Rube C, Weissbach L, Althaus P, Rebmann U, Kalble T, Feldmann HJ, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009;27(27):2924–2930.
    1. Lughezzani G, Briganti A, Karakiewicz PI, Kattan MW, Montorsi F, Shariat SF, Vickers AJ. Predictive and prognostic models in radical prostatectomy candidates: a critical analysis of the literature. European urology. 2010;58(58):687–700.
    1. Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, Bergstralh EJ, Kollmeyer TM, Fink S, Haddad Z, Zimmermann B, Sierocinski T, Ballman KV, Triche TJ, Black PC, Karnes RJ, et al. Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy. PLoS One. 2013 Accepted.
    1. Ghadessi M, Bergstralh EJ, Erho N, Crisan A, Davicioni E, Buerki C, Mitra AP, Thompson DJS, Carlson R, Haddad Z, Zimmermann B, Ballman KV, Kollmeyer TM, Sierocinski T, Vergara IA, Triche TJ, et al. Validation of a genomic classifier that predicts metastatic disease progression in men with high-risk pathologic features postprostatectomy. Journal of Clinical Oncology. 2013;31(suppl 6) abstr 36.
    1. Davicioni E, Ghadessi M, Bergstralh EJ, Buerki C, Mitra AP, Crisan A, Erho N, Vergara IA, Carlson R, Thompson DJS, Haddad Z, Zimmermann B, Sierocinski T, Triche TJ, Fink S, Kollmeyer TM, et al. Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. In submission. 2013
    1. Hornberger J, Doberne J, Chien R. Laboratory-developed test--SynFRAME: an approach for assessing laboratory-developed tests synthesized from prior appraisal frameworks. Genetic testing and molecular biomarkers. 2012;16(16):605–614.
    1. enetic Testing. ACCE model system for collecting analyzing and disseminating information on genetic tests. 2007 CDC.
    1. Ross AE, Ghadessi M, Davicioni E, Crisan A, Buerki C, Erho N, Mitra AP, Thompson DJS, Triche TJ, Schaeffer EM, Feng FYC. Validation of a genomic classifier that predicts metastatic disease progression in men with biochemical recurrence post radical prostatectomy. Journal of Clinical Oncology. 2013;31 (suppl 6; abstr 52)
    1. Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group. Genetics in medicine : official journal of the American College of Medical Genetics. 2009;11(11):3–14.
    1. Srivastava G, Renfro LA, Behrens RJ, Lopatin M, Chao C, Soori GS, Dakhil SR, Mowat RB, Kuebler JP, Kim GP, Mazurczak M, Lee M, Alberts SR. Prospective evaluation of a 12-gene assay on treatment recommendations in patients with stage II colon cancer. Journal of Clinical Oncology. 2012;30 (suppl 34, abstr 453)
    1. Hornberger J, Lyman GH, Chien R, Meropol NJ. A Multigene Prognostic Assay for Selection of Adjuvant Chemotherapy in Patients with T3, Stage II Colon Cancer: Impact on Quality-Adjusted Life Expectancy and Costs. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2012;15(15):1014–1021.
    1. Hornberger J, Alvarado MD, Rebecca C, Gutierrez HR, Yu TM, Gradishar WJ. Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review. Journal of the National Cancer Institute. 2012;104(104):1068–1079.
    1. Krupski TL, Foley KA, Baser O, Long S, Macarios D, Litwin MS. Health care cost associated with prostate cancer, androgen deprivation therapy and bone complications. The Journal of urology. 2007;178(4 Pt 1):1423–1428.
    1. Hodges JC, Lotan Y, Boike TP, Benton R, Barrier A, Timmerman RD. Cost-Effectiveness Analysis of SBRT Versus IMRT: An Emerging Initial Radiation Treatment Option for Organ-Confined Prostate Cancer. American Journal of Managed Care. 2012;18 (5 Spec No.2):e186-e193.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit