The Testing Process

Prostate cancer patient journey: When to test?

Germline testing should be considered upon initial diagnosis of prostate cancer, and somatic testing should be performed at presentation of metastatic disease.(1-3) Close collaboration between oncologist, urologist and pathologist and timely testing is critical for successful management of prostate cancer patients.(4)

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2025. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed December 10, 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.
  2. Parker, C. et al. (2020) 'Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up', Annals of Oncology.
  3. Cornford, P. et al. (2024) 'EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer—2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent', Prostate Cancer.
  4. Schostak, M. et al. (2024) 'Practical Guidance on Establishing a Molecular Testing Pathway for Alterations in Homologous Recombination Repair Genes in Clinical Practice for Patients with Metastatic Prostate Cancer', European Urology Oncology.

International guidelines recommend testing for HRR genes

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2025. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed December 10, 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.
  2. Parker, C. et al. (2020) 'Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up', Annals of Oncology.
  3. EAU-EANM-ESTRO-ESUR-ISUP-SIOG (2024) 'Guidelines on Prostate Cancer—2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent'. Available at: https://www.eau.org/guidelines/prostate-cancer (Accessed: 12 February 2025).

HRR gene panels used in PROpel, MAGNITUDE, and TALAPRO-2 clinical trials1-4

Sample source for HRR testing: PROpel, 535 (67.2%) tissue ± ctDNA and 243 (30.5%) ctDNA only; MAGNITUDE, 476 (71.0%) tissue ± ctDNA and 193 (28.8%) ctDNA only; TALAPRO-2, 804 (99.9%) tissue ± ctDNA and 0 (0%) ctDNA only

  1. Clarke, N. et al. (2022) 'Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer', NEJM Evidence.
  2. Chi, K. et al. (2023) 'Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer', Journal of Clinical Oncology.
  3. Agarwal, N. et al. (2023) 'TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)', Abstract LBA17 presented at ASCO GU.
  4. Azad, A. et al. (2023) 'Use of circulating tumor DNA (ctDNA) to complement tumor tissue homologous recombination repair (HRR) gene alteration testing in TALAPRO-2, a phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)', Abstract 5056 presented at ASCO.

Clinical Utility of mutated HRR genes1

FDA Pooled Analysis of HRR Gene Subgroups Across PARPi + ARPi Phase III Studies

ARPI = Androgen Receptor Pathway Inhibitor;  BICR = Blinded Independent Central Review;  HRR = Homologous Recombination Repair;  OS = Overall Survival;  PARPi = Poly(ADP-ribose) Polymerase Inhibitor, rPFS = Radiographic Progression-Free Survival 

  1. Fallah, J. et al. (2024) 'Efficacy of Poly(ADP-ribose) Polymerase Inhibitors by Individual Genes in Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer: A US Food and Drug Administration Pooled Analysis', Journal of Clinical Oncology.

HRR Testing: How to test?

The most important aspect of test selection is to ensure the appropriate genes are analyzed to maximize patient benefit from targeted treatments. Different methodologies can be utilized for HRR biomarker testing. With an increasing number of HRR genes that need to be tested in prostate cancer, there is a shift in the diagnostic field from single gene testing towards simultaneous testing of multiple genes by NGS panels. WES and WGS can provide more comprehensive information on genomic background of prostate cancer patient but would also introduce additional challenges such as prolonged turnaround time, increased costs of testing and complex data analysis/interpretation.

  1. Scott, R.J. et al. (2021) 'Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions', Oncotarget, 12, pp. 1600-1614.
  2. Stewart, M.D. et al. (2022) 'Homologous Recombination Deficiency: Concepts, Definitions, and Assays', Oncologist, 27(3), pp. 167-174.
  3. Myriad Genetics (2025) 'BRACAnalysis CDx®'. Available at: https://myriad.com/genetic-tests/bracanalysiscdx-germline-test/ (Accessed: 12 February 2025).
  4. Sophia Genetics (2025) 'SOPHiA DDM™ Homologous Recombination Applications'. Available at: https://www.sophiagenetics.com (Accessed: 12 February 2025).
  5. AmoyDx (2025) 'HANDLE HRR NGS Panel'. Available at: https://www.amoydx.com (Accessed: 12 February 2025).
  6. Foundation Medicine (2025) 'FoundationOne CDx'. Available at: https://www.foundationmedicine.com/test/foundationone-cdx (Accessed: 12 February 2025).
  7. Foundation Medicine (2025) 'FoundationOne Liquid CDx'. Available at: https://www.foundationmedicine.com/test/foundationone-liquid-cdx (Accessed: 12 February 2025).
  8. Caris Molecular Intelligence (2025) 'Profile Menu Brochure'. Available at: https://www.carismolecularintelligence.com/wp-content/uploads/2017/03/TN0276-v12_Profile-Menu-Brochure.pdf (Accessed: 12 February 2025).
  9. Sosinsky, A. et al. (2024) 'Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme', Nature Medicine.

NGS panel testing is frequently utilized for determining mutations in HRR genes. It is important to have an understanding of the test being performed and the limitations of the assay

HRR = Homologous Recombination Repair, CGP = comprehensive genomic profiling; 
NGS = next generation sequencing; WES = whole exome sequencing; WGS = whole genome sequencing

  1. Singh, R. et al. (2022) 'Target Enrichment Approaches for Next-Generation Sequencing Applications in Oncology', Diagnostics (Basel).

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Reporting the Results

Biomarker test results should be reported in a concise, clear and standardized manner.

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