Precision Medicine for Prostate Cancer
Discover guideline-recommended actionable and emerging biomarkers in prostate cancer.
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Biomarker Testing is Transforming the Management of Prostate Cancer
Prostate cancer is the 2nd most frequent cancer in men...1
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and the 5th leading cause of death worldwide.1
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Nearly 9 in 10 patients with advanced prostate cancer have potentially actionable
biomarkers that can help to guide clinical management.2–4
Test All Patients With Metastatic Prostate Cancer for Homologous Recombination Repair Mutations (HRRm), Including BRCA1/2 6
Homologous recombination repair gene mutations (HRRm), such as mutations in BRCA1 or BRCA2, and ATM, may play a role in the progression from localized disease to metastatic castration-resistant prostate cancer.4 Testing specifically for HRRm may have familial, prognostic, and therapeutic implications for patients with prostate cancer.2,5
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for
Prostate Cancer recommend tumor testing for all patients with metastatic
prostate cancer5,6
Clinically localized prostate cancer
Workup that includes:
Inquiry about family and personal history of cancer, and known germline variants at initial diagnosis
Germline testing
in patients with known history of familial cancer or familial cancer risk mutationsa,b
Metastatic prostate cancer
Regional prostate cancer
Workup that includes:
Inquiry about family and personal history of cancer, and known germline variants at initial diagnosis
Somatic testingc,d,e
for HRR mutationsf
Regional
Metastatic
Germline testing
in all patients with metastatic or regional (node positive), high-risk/very high-risk localized prostate cancerb
Unfeasible biopsy
ctDNA
Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2024. ©2024. National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
Footnotes
aFamilial cancer risk mutations: BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, and HOXB13.6 bGermline testing is recommended for patients with prostate cancer and a positive family history, or Ashkenazi Jewish ancestry, or a personal history of breast cancer.7 cTumor testing can be considered for regional prostate cancer.6 dTumor testing for MSI-H or dMMR is recommended in patients with metastatic castration-resistant prostate cancer and may be considered in patients with regional or castration-sensitive metastatic prostate cancer.6 eTMB testing may be considered in patients with metastatic castration-resistant prostate cancer.6 fHRR genes: BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12.6
ATM, ataxia-telangiectasia mutated; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDK12, cyclin-dependent kinase 12; CHEK2, checkpoint kinase 2; ctDNA, circulating tumor deoxyribonucleic acid; dMMR, deficient mismatch repair; FANCA, fanconi anemia complementation group A; HOXB13, homeobox 13; HRR, homologous recombination repair; HRRm, homologous recombination repair mutation; MLH1, MutL homolog 1; MSH2/6, MutS homolog 2 and/or 6; MSI-H, microsatellite instability-high; NCCN, National Comprehensive Cancer Network® (NCCN®); PALB2, partner and localizer of BRCA2; PMS2, postmeiotic segregation increased 2; RAD51D, RAD51 paralog D; TMB, tumor mutational burden.
Test the Tumor at Metastatic Diagnosis for HRRm – Including BRCA1/2 6
These biomarkers are actionable in metastatic castration-resistant prostate cancer6:
| What to test6 | Whom to test6 | How to test8-11 | When to test6 |
|---|---|---|---|
| Somatic mutations in HRR genes (BRCA1, BRCA2, ATM, PALB2, FANCL, RAD51D, CHEK2, and CDK12) |
| FDA-approved CDx8,9:
| Recommended in patients with metastatic prostate cancer and can be considered in patients with regional prostate cancer |
| Germline mutations in HRR genes, such as BRCA1/2 |
| FDA-approved CDx10:
| Criteria for germline testing should be reviewed at time of initial diagnosis and, if relevant, at recurrence |
| MSI and dMMR genes (MLH1, MSH2, MSH6, and PMS2) |
| FDA-approved CDx8,11:
|
This document is intended as educational information and is not intended as a complete list of available testing options. AstraZeneca is not responsible for any test provider and does not endorse any particular diagnostic test. The accuracy and results of diagnostic tests vary, and AstraZeneca shall have no liability arising from such testing. Information provided herein should in no way be considered a guarantee of coverage, reimbursement, or patient assistance. Providers should contact third-party laboratories for information on their patient assistance programs. While diagnostic testing may assist providers in identifying appropriate treatment for patients, the decision and action should be decided by a provider in consultation with the patient. All products are trademarks of their respective holders, all rights reserved.
ATM, ataxia-telangiectasia mutated; BRCA1/2, BReast CAncer susceptibility gene 1/2; CDK12, cyclin-dependent kinase 12; CDx, companion diagnostic; CHEK2, checkpoint kinase 2; dMMR, deficient mismatch repair; FANCA, fanconi anemia complementation group A; FDA, US Food and Drug Administration; HRR, homologous recombination repair; HRRm, homologous recombination repair mutation; MLH1/2/6, MutS homolog 1, 2, and/or 6; MSI, microsatellite instability; PALB2, partner and localizer of BRCA2; RAD51D, RAD51 paralog D.
Nearly a Third of Patients With Primary or Metastatic Prostate Cancer Have an HRR Mutation12
BRCA1/2 mutations are seen in ~15% of patients with advanced disease12
61.1%
No DDR alterations detected
15.2%
BRCA1/2a
17.7%
Other HRR genes
6%
MMR
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aBRCA1 and BRCA2 prevalence is 1.9% and 13.3%, respectively.12
BRCA1/2, BReast CAncer susceptibility gene 1/2; DDR, DNA damage response; HRR, homologous recombination repair; MMR, mismatch repair.
Testing for HRR Mutations Provides Predictive, Prognostic, and Familial Insights
Mutations in the BRCA1/2 genes of the HRR pathway can indicate eligibility for targeted treatment in certain patients with prostate cancer.12
BRCA1/2, BReast CAncer susceptibility gene 1/2; BRCA1/2m, BReast CAncer susceptibility gene 1/2 mutation; HRR, homologous recombination repair.
Considerations for Your Practice
As recommended by NCCN Guidelines®6:
- Include somatic multigene tumor testing to detect alterations in HRR genes in metastatic prostate cancer; it can also be considered in regional disease
- Review criteria for germline multigene testing at initial diagnosis and, if relevant, at recurrence
- Arrange for post-test genetic counseling if a pathogenic variant is identified, or if there is positive family history
- Review protocols for identifying patients eligible for biomarker testing, such as BRCA1/2 mutations.
- Involve the MDT early to enable optimal workflow for specimen selection and preservation at time of diagnosis and ensure suitability for testing at the critical point of clinical decision-making.13
BRCA1/2, BReast CAncer susceptibility gene 1/2; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network® (NCCN®).
Helpful Resources
Check out these featured resources on biomarker testing in prostate cancer.
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FOR HCPS
Optimizing biomarker testing for patients with metastatic prostate cancerLearn how biomarker testing for mutations in homologous recombination repair (HRR) genes, such as BReast CAncer susceptibility gene 1/2 (BRCA1/2) may be used to help guide treatment decisions.
FOR HCPS
Testing for homologous recombination repair mutations (HRRm), including BReast CAncer susceptibility gene 1/2 (BRCA1/2), can help guide treatment options in advanced prostate cancer.Use this interactive PDF as a comprehensive resource for detailed information on prostate cancer and genetic testing.
FOR HCPS
Biomarker testing recommendations for advanced prostate cancerReview guideline-recommended testing for BReast CAncer susceptibility gene 1/2 (BRCA1/2) and other homologous recombination repair (HRR) gene mutations to help inform treatment decision-making.
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Connect with usReferences
- Lin S, et al. Epidemiol Health. 2023;45:e2023038.
- Cucchiara V, et al. Eur Urol. 2018;73(4):572–582.
- Concepcion R. Urology Times. 2020;9(1). Accessed Sept 25, 2024. https://www.urologytimes.com/view/role-and-rationale-molecular-testing-advanced-prostate-cancer
- Palmbos PL, Hussain MH. Oncology (Williston Park). 2016;30(5):377–385.
- Cheng HH, et al. J Natl Compr Canc Netw. 2019;17(5):515–521.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 03, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate V.2.2025. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed November 07, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.
- Foundation Medicine. Foundation One® CDx Technical Specifications. Accessed Sept 25, 2024. https://www.foundationmedicine.com/sites/default/files/media/documents/2024-01/F1CDxTechnicalSpecificationsSPEC-01197.pdf
- Foundation Medicine. Foundation One® Liquid CDx Technical Specifications. Accessed Sept 25, 2024. https://www.foundationmedicine.com/sites/default/files/media/documents/2023-10/F1LCDx_Technical_Specs_072021-2.pdf
- Myriad Genetic Laboratories. BRACAnalysis CDx® Technical Information. Accessed Sept 25, 2024. https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140020S020C.pdf
- Roche Diagnostics. Ventana MMR RxDx Panel. Accessed Sept 25, 2024. https://diagnostics.roche.com/global/en/products/tests/ventana-mmr-rxdx-panel.html
- Lozano R, et al. Br J Cancer. 2021;124(3):552–563.
- Sciarra A, et al. Am J Clin Exp Urol. 2013;1(1):12–17.
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.