Germline and somatic genomic testing for metastatic prostate cancer: ASCO guideline
Abstract
ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations. METHODS: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications. RESULTS: A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials. RECOMMENDATIONS: Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor v metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .
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Current guidelines support both germline and somatic panel-based sequencing for men with metastatic prostate cancer because these tests can identify molecular alterations linked to approved or potentially actionable therapies.
“Current guidelines support both germline and somatic panel-based sequencing for men with metastatic prostate cancer because these tests can identify molecular alterations linked to approved or potentially actionable therapies [2, 3].”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
Successful implementation of mainstreaming models depends on assay literacy, clear referral pathways, and communication structures that ensure pathogenic findings are translated into appropriate therapeutic decisions and familial risk management.
“However, successful implementation depends on assay literacy, clear referral pathways, and communication structures that ensure pathogenic findings are translated into appropriate therapeutic decisions and familial risk management rather than remaining isolated laboratory results [2].”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
In advanced prostate cancer, germline and somatic testing identify predictive biomarkers linked to therapy selection.
“in advanced disease, germline and somatic testing identify predictive biomarkers linked to therapy selection”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
Traditional risk stratification using prostate-specific antigen, grade group, and stage incompletely captures tumor biology and does not fully explain heterogeneity within nominal clinical risk groups.
“Traditional risk stratification using prostate-specific antigen, grade group, and stage remains indispensable; however, these measures incompletely capture tumor biology and do not fully explain the heterogeneity observed within nominal clinical risk groups [2, 3].”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
These findings support broader genomic evaluation strategies, particularly in high-risk and metastatic settings.
“These findings support broader genomic evaluation strategies, particularly in high-risk and metastatic settings [2, 3].”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
In metastatic disease, germline and somatic sequencing are recommended to identify actionable alterations such as HRD and dMMR/MSI-H, which have direct implications for PARP inhibitor therapy and immune checkpoint blockade.
“In metastatic disease, genomic testing shifts toward predictive biomarkers. Germline and somatic sequencing are recommended to identify actionable alterations such as homologous recombination repair deficiency (HRD) and mismatch repair deficiency (dMMR/MSI-H), which have direct implications for PARP inhibitor therapy and immune checkpoint blockade [2, 8–10].”
From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [2]
Cites
Patient-clinician communication: American Society of Clinical Oncology consensus guideline
Gilligan, T., Coyle, N., Frankel, R. M., Berry, D. L., Bohlke, K., Epstein, R. M., Finlay, E., Jackson, V. A., Lathan, C. S., Loprinzi, C. L., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.2311 · Cited by 610 · see citing works
Rucaparib or Physician’s Choice in Metastatic Prostate Cancer
Fizazi, K., Piulats, J. M., Reaume, M. N., Ostler, P., McDermott, R., Gingerich, J. R., Pintus, E., Sridhar, S. S., Bambury, R. M., Emmenegger, U., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2214676 · Cited by 449 · see citing works
Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer
Clarke, N. W., Armstrong, A. J., Thiery-Vuillemin, A., Oya, M., Shore, N., Loredo, E., Procopio, G., de Menezes, J., Girotto, G., Arslan, C., et al. (2022) · NEJM Evidence · doi:10.1056/evidoa2200043 · Cited by 426 · see citing works
Synthesising quantitative evidence in systematic reviews of complex health interventions
Higgins, J. P. T., López-López, J. A., Becker, B. J., Davies, S. R., Dawson, S., Grimshaw, J. M., McGuinness, L. A., Moore, T. H. M., Rehfuess, E. A., Thomas, J., et al. (2019) · BMJ Global Health · doi:10.1136/bmjgh-2018-000858 · Cited by 322 · see citing works
Racial differences in genomic profiling of prostate cancer
Mahal, B. A., Alshalalfa, M., Kensler, K. H., Chowdhury-Paulino, I., Kantoff, P., Mucci, L. A., Schaeffer, E. M., Spratt, D., Yamoah, K., Nguyen, P. L., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2000069 · Cited by 126 · see citing works
Self-citationAlpert, A. B., Gampa, V., Lytle, M. C., Manzano, C., Ruddick, R., Poteat, T., Quinn, G. P., & Kamen, C. S. (2021) · Patient Education and Counseling · doi:10.1016/j.pec.2021.03.007 · Cited by 73 · see citing works
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A decision-oriented framework for genomic testing across the prostate cancer continuum
Cobran, E. K., Samadder, N. J., Schaid, D. J., Conti, D. V., Haiman, C., Vargas, L., Gionfriddo, M. R., & Tilburt, J. C. (2026) · Cancer Genetics · doi:10.1016/j.cancergen.2026.06.002 · Cited by 1 · see citing works
- Authors
- Yu, E. Y., Rumble, R. B., Agarwal, N., Cheng, H. H., Eggener, S. E., Bitting, R. L., Beltran, H., Giri, V. N., Spratt, D., Mahal, B., Lu, K., Crispino, T., & Trabulsi, E. J.
- Affiliations
- University of Washington and Fred Hutchinson Cancer Center, Seattle, WA
- American Society of Clinical Oncology, Alexandria, VA
- Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT
- University of Chicago, Chicago, IL
- Duke Cancer Institute, Durham, NC
- Dana Farber Cancer Institute, Boston, MA
- Yale School of Medicine and Yale Cancer Center, New Haven, CT
- UH Cleveland Medical Center, Cleveland, OH
- UM/Sylvester Comprehensive Cancer Center, Miami, FL
- Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung City, Taiwan
- Patient Representative, Chapter President UsTOO Las Vegas, Prostate Cancer Education and Support, Las Vegas, NV
- Jefferson Einstein Medical Center, Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2025-02-20
- Volume
- 43
- Issue
- 6
- Pages
- 748-758
- ISSN
- 0732-183X
- 1527-7755
- Cited by
- 63
- References
- 6
- Language
- en
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