Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.
A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score.
Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19–1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19–1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79–4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71.
Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.
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Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, Allen C, et al. Global, regional, and National Cancer Incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 Cancer Groups, 1990 to 2016. JAMA Oncol. 2018;4:1553.
Patrikidou A, Loriot Y, Eymard JC, Albiges L, Massard C, Ileana E, et al. Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17:348–52.
Reese AC, Pierorazio PM, Han M, Partin AW. Contemporary evaluation of the national comprehensive cancer network prostate cancer risk classification system. Urology. 2012;80:1075–9.
Sundi D, Tosoian JJ, Nyame YA, Alam R, Achim M, Reichard CA, et al. Outcomes of very high-risk prostate cancer after radical prostatectomy: validation study from 3 centers. Cancer. 2019;125:391–7.
Mahal BA, Butler S, Franco I, Spratt DE, Rebbeck TR, D’Amico AV, et al. Use of active surveillance or watchful waiting for low-risk prostate cancer and management trends across risk groups in the United States, 2010-2015. JAMA. 2019;321:704–6.
Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA. 2015;314:80–2.
Rosenthal SA, Hu C, Sartor O, Gomella LG, Amin MB, Purdy J, et al. Effect of chemotherapy with docetaxel with androgen suppression and radiotherapy for localized high-risk prostate cancer: the randomized phase III NRG oncology RTOG 0521 trial. J Clin Oncol. 2019;37:1159–68.
James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.
McKay RR, Ye H, Xie W, Lis R, Calagua C, Zhang Z, et al. Evaluation of intense androgen deprivation before prostatectomy: a randomized Phase II trial of enzalutamide and leuprolide with or without abiraterone. J Clin Oncol. 2019;37:923–31.
Eastham JA, Heller G, Halabi S, Monk JP, Beltran H, Gleave M, et al. CALGB 90203 (ALLIANCE): radical prostatectomy with or without neoadjuvant chemohormonal therapy in men with clinically localized, high risk prostate cancer. J Urol. 2019;201. https://doi.org/10.1097/01.ju.0000557504.00464.d6.
Spratt DE, Zhang J, Santiago-Jiḿenez M, Dess RT, Davis JW, Den RB, et al. Development and validation of a novel integrated clinical-genomic risk group classification for localized prostate cancer. J Clin Oncol. 2018;36:581–90.
Spratt DE, Yousefi K, Deheshi S, Ross AE, Den RB, Schaeffer EM, et al. Individual patient-level meta-analysis of the performance of the decipher genomic classifier in high-risk men after prostatectomy to predict development of metastatic disease. J Clin Oncol. 2017;35:1991–8.
Berlin A, Murgic J, Hosni A, Pintilie M, Salcedo A, Fraser M, et al. Genomic classifier for guiding treatment of intermediate-risk prostate cancers to dose-escalated image guided radiation therapy without hormone therapy. Int J Radiat Oncol Biol Phys. 2019;103:84–91.
Feng FY, Thomas S, Gormley M, Lopez-Gitlitz A, Yu MK, Cheng S, et al. Identifying molecular determinants of response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the SPARTAN trial. J Clin Oncol. 2019;37:42–2.
Cooperberg MR, Erho N, Chan JM, Feng FY, Fishbane N, Zhao SG, et al. The diverse genomic landscape of clinically low-risk prostate cancer. Eur Urol 2018. https://doi.org/10.1016/j.eururo.2018.05.014.
Mohler J, Antonarakis E, Armstrong A, D’Amico A. NCCN clinical practice guidelines in oncology: prostate cancer. 2019: http://www.nccn.org/professionals/physician_gls.
Sundi D, Wang VM, Pierorazio PM, Han M, Bivalacqua TJ, Ball MW, et al. Very-high-risk localized prostate cancer: definition and outcomes. Prostate Cancer Prostatic Dis. 2013;17:1–7.
Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016;40:244–52.
Klein EA, Haddad Z, Yousefi K, Lam LL, Wang Q, Choeurng V, et al. Decipher genomic classifier measured on prostate biopsy predicts metastasis risk. Urology 2016. https://doi.org/10.1016/j.urology.2016.01.012.
Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS ONE 2013;8. https://doi.org/10.1371/journal.pone.0066855.
Ross AE, Johnson MH, Yousefi K, Davicioni E, Netto GJ, Marchionni L, et al. Tissue-based genomics augments post-prostatectomy risk stratification in a natural history cohort of intermediate- and high-risk men. Eur Urol. 2016;69:157–65.
Cooperberg MR, Lubeck DP, Mehta SS, Carroll PR, Kantoff PW, Smith MR, et al. Time trends in clinical risk stratification for prostate cancer: implications for outcomes (data from CaPSURE). J Urol. 2003;170:S21–7.
Yossepowitch O, Eggener SE, Serio AM, Carver BS, Bianco FJ, Scardino PT, et al. Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy. Eur Urol. 2008;53:950–9.
Nabid A, Carrier N, Martin A-G, Bahary J-P, Lemaire C, Vass S, et al. Duration of androgen deprivation therapy in high-risk prostate cancer: a randomized phase III trial. Eur Urol. 2018;74:432–41.
Nguyen PL, Haddad Z, Ross AE, Martin NE, Deheshi S, Lam LLC, et al. Ability of a genomic classifier to predict metastasis and prostate cancer-specific mortality after radiation or surgery based on needle biopsy specimens. Eur Urol. 2017;72:845–52.
Karnes RJ, Choeurng V, Ross AE, Schaeffer EM, Klein EA, Freedland SJ, et al. Validation of a genomic risk classifier to predict prostate cancer-specific mortality in men with adverse pathologic features. Eur Urol. 2018;73:168–75.
Lotan TL, Wei W, Morais CL, Hawley ST, Fazli L, Hurtado-Coll A, et al. Pten loss as determined by clinical-grade immunohistochemistry assay is associated with worse recurrence-free survival in prostate cancer. Eur Urol Focus. 2016;2:180–8.
Hamid AA, Gray KP, Shaw G, MacConaill LE, Evan C, Bernard B, et al. Compound genomic alterations of TP53, PTEN, and RB1 tumor suppressors in localized and metastatic prostate cancer. Eur Urol. 2019;76:89–97.
Patel HD, Tosoian JJ, Carter HB, Epstein JI. Adverse pathologic findings for men electing immediate radical prostatectomy defining a favorable intermediate-risk group. JAMA Oncol. 2018;4:89–92.
Knudsen BS, Kim HL, Erho N, Shin H, Alshalalfa M, Lam LLC, et al. Application of a clinical whole-transcriptome assay for staging and prognosis of prostate cancer diagnosed in needle core biopsy specimens. J Mol Diagn. 2016;18:395–406.
We would like to thank the National Institutes of Health/National Cancer Institute Advanced Training in Urologic Oncology Grant (JJT, T32/CA180984), Prostate Cancer Foundation (BAM, DES), the Prostate Cancer NIH SPORE (DES, P50CA186786), and the Department of Defense (DES, PC151068).
Conflict of interest
Nonrelevant conflicts of interest will be disclosed in the ICMJE forms. JJT: Leadership role with equity interest: LynxDx, Inc. SJF: Research funding: Decipher Biosciences. SGZ: Travel/expenses and patent applications pending with Decipher Biosciences. TMM: Research funding: Myriad Genetics, GenomeDx. EMS: Consultant: Abbvie. DES: Advisory board: Blue Earth,Janssen, and AstraZenica. Funding: Janssen.
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Tosoian, J.J., Birer, S.R., Jeffrey Karnes, R. et al. Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier. Prostate Cancer Prostatic Dis 23, 646–653 (2020). https://doi.org/10.1038/s41391-020-0226-2