Germline and Somatic Genomic Testing for Metastatic Prostate Cancer
Publication Date: January 9, 2025
Last Updated: January 14, 2025
Diagnosis
Summary of Recommendations
- General Note: The following recommendations (strong or conditional/weak) and terminology represent reasonable options for patients depending on clinical circumstances and in the context of individual patient preferences. Recommended care should be accessible to patients whenever possible.
Recommendation 1: All patients with metastatic prostate cancer should undergo germline genetic testing with next generation sequencing technologies. (H, S)
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Recommendation 2: Those patients with metastatic prostate cancer (both castration-sensitive prostate cancer [CSPC] and castration-resistant prostate cancer [CRPC]) who are being considered for biomarker-directed systemic treatment should undergo somatic testing with next generation sequencing technologies. (H, S)
Practical information for Recommendation 2: While there are no current U.S. Food and Drug Administration (FDA) -approved biomarker directed treatments following somatic testing for metastatic castration-sensitive prostate cancer (mCSPC), somatic testing may be warranted in the presence of high-volume disease or where there is a high likelihood the patient’s disease will progress to CRPC, where the patient is a candidate for future treatment with a biomarker directed therapy (poly(ADP-ribose) polymerase [PARP] inhibitor or checkpoint inhibitor).
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Recommendation 3: The panel recommends that sequential somatic testing may be offered when there has been a meaningful change in the patient’s status or treatment plan, especially in cases where prior tests were negative or uninformative (e.g., insufficient or low tumor content). (M, W)
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Recommendation 4: Archival tissue samples are preferred in initial testing. Circulating tumor DNA (ctDNA) is preferred when there is no accessible metastatic site to biopsy or for sequential testing. In the setting of minimal disease burden associated with low ctDNA fraction, metastatic biopsy is preferred. (L, W)
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Recommendation 5: Patients with pathogenic germline variants or somatic alterations in BRCA1 and BRCA2 demonstrate poorer outcomes but are candidates for treatment with PARP inhibitor monotherapy, PARP inhibitor with androgen receptor pathway inhibitor (ARPI) combination therapy, and platinum-based agents. (H, S)
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Recommendation 6: Treatment recommendations should not be made based on prognostic only biomarkers. However, they may be considered for directing patients to clinical trials. Germline information may still be important for patient counseling, informing hereditary risk for patients and families. (H, S)
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The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
Title
Germline and Somatic Genomic Testing for Metastatic Prostate Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
January 9, 2025
Last Updated Month/Year
January 14, 2025
Country of Publication
US
Document Objectives
To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.
Target Patient Population
Patients with metastatic prostate cancer
Target Provider Population
Clinicians providing care to patients with metastatic prostate cancer
PICO Questions
Who should receive germline testing with next-generation sequencing (NGS) technologies?
Who should receive somatic testing with NGS technologies?
Who should receive sequential somatic testing with NGS technologies?
What are the strengths and weaknesses of primary tumor archival tissue versus fresh metastatic biopsy tissue versus circulating tumor DNA (ctDNA) testing for somatic testing?
What are the key therapeutic implications of germline or somatic testing for single-gene genetic variants (eg, BRCA1, BRCA2)?
What are the key prognostic implications of germline or somatic testing?
Inclusion Criteria
Male, Adult, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Genetics, nurse, nurse practitioner, physician, physician assistant
Diseases/Conditions (MeSH)
D011467 - Prostate
Keywords
Metastatic Prostate Cancer, hereditary cancer risk, somatic genomic testing, germline genetic testing
Source Citation
Yu EY, Rumble RB, Agarwal N, et al. Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline. J Clin Oncol. 2025 Jan 09. doi:10.1200/JCO.24.02608.