Precision Medicine for Prostate Cancer

Biomarker Testing is Transforming the Management of Prostate Cancer

Prostate cancer is the 2^nd most frequent cancer in men...¹

and the 5^th leading cause of death worldwide.^2,3

Nearly 9 in 10 patients with advanced prostate cancer have potentially actionable

biomarkers that can help to guide clinical management in metastatic castration-resistant prostate cancer (mCRPC).⁴

Routinely Test All Patients With Metastatic Prostate Cancer for Prognostic PTEN Alterations and Other Recommended Mutations^3,5-9

In a real-world study examining multiple alterations in patients with mHSPC, the PTEN tumor suppressor gene was found to be among the most common. Homologous recombination repair gene mutations (HRRm), such as mutations in BRCA1, BRCA2, or ATM, playing a role in the progression from localized disease to metastatic castration-resistant prostate cancer. Testing specifically for PTEN alteration and HRRm may have familial, prognostic, and therapeutic implications for patients with prostate cancer.^3,5-9

^aFamilial cancer risk mutations: BRCA1, BRCA2, ATM, PALB2, CHEK2, and HOXB13.^{11 b}Germline testing is recommended for patients with prostate cancer and a positive family history of certain cancers, Ashkenazi Jewish ancestry, or a personal history of breast cancer.^{11 c}Tumor testing can be considered for regional prostate cancer.^{10 d}Tumor 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.^{10 e}TMB testing is recommended in patients with metastatic castration-resistant prostate cancer.^{10 f}HRR genes including, but not limited to: BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12.¹⁰

Test the Tumor at Metastatic Diagnosis for PTEN and HRRm—Including BRCA1/2 ⁹

PTEN is an important emerging biomarker in mHSPC¹²

What to test^12,13	Whom to test¹⁴	How to test^{9, 14-17}	When to test⁹
PTEN loss (by IHC, NGS, or FISH)	All patients with metastatic castration-resistant prostate cancer (mCRPC)	IHC for PTEN protein loss NGS for PTEN mutation or deletion FISH for PTEN gene deletion (10q23)	At metastatic diagnosis

These biomarkers are actionable in metastatic hormone-sensitive prostate cancer¹²:

What to test¹⁰	Whom to test^10,11	How to test^18-21	When to test¹⁰
Somatic mutations in HRR genes (BRCA1, BRCA2, ATM, PALB2, FANCL, RAD51D, CHEK2, and CDK12) this is not limited to just the genes that have been listed	All patients with metastatic prostate cancer Could be considered in patients with regional disease	FDA-approved CDx: FoundationOne^®CDx FoundationOne^®Liquid CDx Assesses only BRCA1/2 and ATM	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	All patients with metastatic or regional (node-positive), high-risk/very high-risk localized prostate cancer Patients with prostate cancer and a positive family history of certain cancers, Ashkenazi Jewish ancestry, or a personal history of breast cancer	FDA-approved CDx: BRACAnalysis CDx^® (Myriad Genetics Laboratories, Inc.)	Criteria for germline testing should be reviewed at time of initial diagnosis and, if relevant, at recurrence
Somatic mutations in MSI and dMMR genes (MLH1, MSH2, MSH6, and PMS2)	Patients with metastatic castration-resistant prostate cancer May be considered in patients with regional or castration-sensitive metastatic prostate cancer	FDA-approved CDx: dMMR genes: Roche/Ventana MMR RxDx Panel MSI: FoundationOne^®CDx

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; FANCL, fanconi anemia, complementation group L; FDA, US Food and Drug Administration; FISH, fluorescence in situ hybridization; HRR, homologous recombination repair; HRRm, homologous recombination repair mutation; IHC, immunohistochemistry; MLH1/2/6, MutS homolog 1, 2, and/or 6; MSI, microsatellite instability; NGS, next-generation sequencing; PALB2, partner and localizer of BRCA2; PTEN, phosphatase and tensin homolog; RAD51D, RAD51 paralog D.

^aBRCA1 and BRCA2 prevalence is 1.9% and 13.3%, respectively.²⁵

Considerations for Your Practice

Biomarker utilization and pathologist expertise contributes to:

The creation of consensus guidelines to improve testing, ordering, and reporting standardization
Expertise in the use of advanced molecular testing
New perspectives on samples and quality
Elevated involvement in institutions and/or tumor board committees
Expanded role and impact within professional societies
Upgraded guidance on implications of tests and targeted treatments through MDT collaboration
Ensure that your lab's order form is updated when your lab has validated/verified a new test and is offering it
Confirm that reports contain relevant information for HCPs, including potential prognostic or treatment implications of biomarker test results

As recommended by NCCN Guidelines^®10:

Review the NCCN Guidelines and test all patients with mPC for prognostic biomarkers at diagnosis and/or progression
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 PTEN-deficiency 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.²⁶

BRCA1/2, BReast CAncer susceptibility gene 1/2; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network^® (NCCN^®);

PTEN, phosphatase and tensin homolog.

BRCA1/2, BReast CAncer susceptibility gene 1/2; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network^® (NCCN^®); PTEN, phosphatase and tensin homolog.

McDowell S. Cancer in men: prostate cancer is #1 for 118 countries globally. American Cancer Society. Published April 17, 2025. Accessed April 17, 2025.
Rawla P. World J Oncol. 2019;10(2):63-89.
Cucchiara V, et al. Eur Urol. 2018;73(4):572-582.
Robinson D, et al. Cell. 2015;161(5):1215-1228.
Thouvenin J, et al. Ann Oncol. 2021;32:S661.
Serritella AV, et al. Prostate Cancer Prostatic Dis. 2025;28:601-609.
Jamaspishvili T, et al. Nat Rev Urol. 2018;15:222-234.
Xu J, et al. Prostate. 2025;85(12):1087-1095.
Yu EY, et al. J Clin Oncol. 2025;43(6):748-758.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Prostate Cancer V.5.2026. ©National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed April 28, 2026. 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.3.2026. ©National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed April 28, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org.
Wise HM, et al. Clin Sci (Lond). 2017;131:197-210.
de Bono J, et al. 2021. Presented at ASCO-GU Cancers Symposium 2021. Abstract #13.
Gupta S, et al. JCO Precis Oncol. 2024;8:e2300562.
Lotan TL, et al. Oncotarget. 2017;8(39):65566-65576.
Lotan TL, et al. Mod Pathol. 2016;29(8):904-914.
Yoshimoto M, et al. Br J Cancer. 2007;97(5):678-685.
Foundation Medicine. Foundation One^® Liquid CDx Technical Specifications. Accessed January 27, 2026. 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 January 27, 2026. https://www.accessdata.fda.gov/cdrh_docs/pdf14/P140020S020C.pdf
Foundation Medicine. Foundation One^® Liquid CDx Technical Specifications. Accessed January 27, 2026. https://www.foundationmedicine.com/sites/default/files/media/documents/2023-10/F1LCDx_Technical_Specs_072021-2.pdf
CDx Roche Diagnostics. Ventana MMR RxDx Panel. Accessed January 27, 2026. https://diagnostics.roche.com/global/en/products/tests/ventana-mmr-rxdx-panel.html
Stopsack KH, et al. Clin Cancer Res. 2020;26(13):3230-3238.
Fizazi K, et al. Ann Oncol. 2026;37(1):53-68.
Hoxhaj G, Manning BD. Nat Rev Cancer. 2020;20:74-88.
Lozano R, et al. Br J Cancer. 2021;124(3):552-563.
Sciarra A, et al. Am J Clin Expo 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.

Precision Medicine for Prostate Cancer

Biomarker Testing is Transforming the Management of Prostate Cancer

Routinely Test All Patients With Metastatic Prostate Cancer for Prognostic PTEN Alterations and Other Recommended Mutations^3,5-9

Test the Tumor at Metastatic Diagnosis for PTEN and HRRm—Including BRCA1/2 ⁹

Biomarker Prevalence

~1/4

~1/3

Testing for Alterations and HRR Mutations Provides Predictive, Prognostic, and Familial Insights

Considerations for Your Practice

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Precision Medicine for Prostate Cancer

Biomarker Testing is Transforming the Management of Prostate Cancer

Routinely Test All Patients With Metastatic Prostate Cancer for Prognostic PTEN Alterations and Other Recommended Mutations3,5-9

Footnotes

Test the Tumor at Metastatic Diagnosis for PTEN and HRRm—Including BRCA1/2 9

Biomarker Prevalence

~1/4

~1/3

Footnotes

Testing for Alterations and HRR Mutations Provides Predictive, Prognostic, and Familial Insights

Considerations for Your Practice

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Routinely Test All Patients With Metastatic Prostate Cancer for Prognostic PTEN Alterations and Other Recommended Mutations^3,5-9

Test the Tumor at Metastatic Diagnosis for PTEN and HRRm—Including BRCA1/2 ⁹