Guidance on Who and When to
Test for HRRm
Who and when to test for HRRm
Who to test
According to the NCCN Guidelines®, all patients with metastatic prostate cancer should be tested for HRR somatic and germline gene alterations.1
When to test
NCCN Guidelines recommend:
- Testing for somatic HRR gene alterations at the time of metastatic prostate cancer diagnosis, and retesting may be considered upon progression to mCRPC1
- Testing for germline mutations in all PC patients with a positive family history of certain cancers or familial cancer risk mutation, high-risk localized or regional PC patients, and all metastatic PC patients1
Test early in prostate cancer1
See below for NCCN Guidelines-based HRR testing-related guidelines for your practice.
If your patient progressed to:
Localized disease
- If your patient has1:
- High- or very high-risk or regional node-positive disease
- A relevant personal or family history
- Perform a germline test
- It can be used to assess risk and prognosis, determine familial risk, and guide treatment selection.1
- Genetic counseling is strongly recommended if a germline mutation (pathogenic or likely pathogenic) is identified; in this case, cascade testing for relatives is critical1
Metastatic disease
- If your patient has progressed to mCSPC or mCRPC1:
-
- Perform both a germline and a somatic test for HRR alterations. If a patient has progressed to mCRPC, look for HRR alterations to identify potential candidates for targeted treatment options.
-
Somatic testing can:
- Offer both prognostic and predictive insights2
- Identify therapy resistance2
- Identify appropriate treatment options1
- Tumor molecular profiles may change with subsequent treatment, and re-evaluation should be considered at disease progression for treatment decision-making1
Germline testing can:
- Identify patients with a worse overall prognosis3-5
- Identify appropriate treatment options1
- Identify family members at increased risk of cancer1
- If germline testing has not already been performed, test all metastatic cancer patients for germline HRR alterations1
HRR, homologous recombination repair; HRRm, homologous recombination repair gene-mutated; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; NCCN, National Comprehensive Cancer Network; PC, prostate cancer.
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.
Vandekerkhove G, Giri VN, Halabi S, et al. Toward informed selection and interpretation of clinical genomic tests in prostate cancer. JCO Precis Oncol 2024;8:e2300654.
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.