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Step up to metastatic
prostate cancer
with HRR gene testing

Testing for HRR gene alterations is an important tool for identifying potential targeted treatment strategies for patients who have progressed to metastatic castration-resistant prostate cancer (mCRPC).1

Scroll down to learn why you should test for HRR alterations.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing all metastatic prostate cancer patients for germline and somatic HRR alterations with a multigene NGS test.2

Know when to test

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What is an HRR gene alteration?

Alterations can occur in genes involved in homologous recombination repair (HRR), which is a pathway involved in DNA repair. HRR gene mutations (HRRm) may encompass alterations in a number of genes, including:

ATM, ATR, BARD1, BRCA1, BRCA2, CDK12, CHEK2, FANCA, FANCL, MLH1, MRE11A, NBN, PALB2, RAD51C, and RAD51D.3,4

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Why test for HRRm

HRR testing can be both prognostic and predictive.2,5

HRR testing can help:

Identify patients who may have worse overall prognosis5-7

Who to test

Identify appropriate treatment options, including HRR-targeted therapies2

See available tests

Identify family members at increased risk of cancer2

How to test

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There are now several FDA-approved and National Comprehensive Cancer Network® (NCCN®)-recommended targeted therapies, such as PARPis, to treat patients with mCRPC with HRR alterations.1,2,8-10

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Percentage of mCRPC patients with an HRR gene alteration

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Based on a comprehensive review of multiple studies and/or pooled datasets reporting the prevalence in mCRPC11,12:

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~ 25

of men with mCRPC have an HRR gene alteration.

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> 50

of HRRm in mCRPC is not BRCA1 or BRCA2.13

Know when to test

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NGS, next-generation sequencing; PARPi, poly (adenosine diphosphate-ribose) polymerase inhibitor.

Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature 2012;481(7381):287-94.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V4.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 29, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. 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.
Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget 2021;12(16):1600-14.
Catalano M, Generali D, Gatti M, et al. DNA repair deficiency as circulating biomarker in prostate cancer. Front Oncol 2023;13:1115241.
Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol 2023;209(6):1082-90.
Plym A, Dióssy M, Szallasi Z, et al. DNA repair pathways and their association with lethal prostate cancer in African American and European American men. JNCI Cancer Spectr 2021;6(1):pka087.
Castro E, Romero-Laorden N, del Pozo A, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2019;37(6):490-503.
Shore N, Oliver L, Shui I, et al. Systematic literature review of the epidemiology of advanced prostate cancer and associated homologous recombination repair gene alterations. J Urol 2021;205(4):977-86.
Leith A, Ribbands A, Kim J, et al. Real-world homologous recombination repair mutation testing in metastatic castration-resistant prostate cancer in the USA, Europe and Japan. Future Oncol 2022;10:2217.
Schostak M, Bradbury A, Briganti A, et al. Practical guidance on establishing a molecular testing pathway for alterations in homologous recombination repair genes in clinical practice for patients with metastatic prostate cancer. Eur Urol Oncol 2024;7(3):344-54.
Chung JH, Dewal N, Sokol E. Prospective comprehensive genomic profiling of primary and metastatic prostate tumors. JCO Precis Oncol 2019;3:PO.18.00283.
de Bono JS, Mehra N, Scagliotti GV, et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol 2021;22(9):1250-64.
Fizazi K, Azad AA, Matsubara N, et al. First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial. Nat Med Published online December 4, 2023. doi:10.1038/s41591-023-02704-x
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