Using Prostate Cancer Gene Testing to Guide Treatment Decisions: Insights as We Head into 2026

By Dr. Christopher Lee, Cancer Care Northwest

As clinicians caring for patients with prostate cancer, we all hear the question asked frequently of us “what would you do if you were in my situation?”  Of course, this is always a challenging question to answer, in that every situation is different and every patient who sits across from us in an exam room has a unique background, medical history, clinical presentation, support and belief system, as well as different genetic makeup. Each patient’s clinical situation is inherently unique from the last patient that we met in the adjacent room. We strive to provide informed recommendations to our patients that are individualized and customized to their specific situation. Genetic testing can help provide clarity in providing clinical recommendations.

Genetic insights continue to transform almost all cancer therapies across a broad spectrum. Most importantly, genetic testing for prostate cancer treatment provides information and guidance to help clinicians better decide (in partnership with their patients) when to screen for patients with familial genetic mutations, if to treat, when to treat, and how to treat. Urologists are uniquely positioned to lead this charge. As national and international guidelines and technology advancements evolve and new therapies emerge, germline testing has become an essential and commonplace tool utilized in most patients, not just for patients with metastatic disease, but also for many with localized cancer.

In 2025, clinical guidelines expanded testing eligibility, new quality measures raised the bar for standard care, and BRCA status became a first-line consideration for selecting advanced therapies, setting the stage for a more personalized, proactive approach in 2026.

The frequency and use of genetic testing for patients with prostate cancer is still trailing behind genetic testing for breast cancer, but this gap is closing as many more clinicians embrace the additional valuable information gained through genetic testing for their patients with prostate cancer. Cancer treatment today is not the same as the cancer treatment your grandfather had 15 or 20 years ago. Because of the recent acceleration in genetic advancements and clinical use, we’re going to look back in 10 years and say ‘Wow, what we knew then was nothing compared to what we now know and understand.’ This is an exciting area of research and will continue to advance in the future.

As practicing clinicians, we see how patients appreciate being given individualized germline, biomarker, and tumor (somatic) genetic testing results. In almost every clinical situation, patients appreciate the time taken to acquire this information for them and their family members so that we can make a well-informed treatment decision together. With respect to tumor testing for prostate cancer, we find that patients have further peace of mind in moving forward with a treatment decision when they have the associated statistics for their specific situation to review.

From identifying candidates with metastatic disease for PARP inhibitors to refining active surveillance decisions, the role of genetic testing now spans the full prostate cancer continuum which continues to evolve heading into 2026.

Who Should Receive Genetic Testing in 2026?

Genetic testing for patients with prostate cancer is about knowing who to test and when to test. Guidelines such as the National Comprehensive Cancer Network^® (NCCN) and the American Society of Clinical Oncology (ASCO) remain cornerstones of evidence-based cancer treatment guidance.

In 2025, both the NCCN and ASCO reinforced a growing consensus: genetic testing is not just for rare cases or late-stage disease. It is a standard-of-care tool for informing decisions across the cancer continuum.

For prostate cancer treatment, the NCCN Clinical Practice Guidelines in Oncology¹ now recommend germline genetic testing for all men with:

• Metastatic prostate cancer
• Regional or node-positive disease
• High- or very high-risk localized prostate cancer.

Additionally, testing is recommended for patients with a prostate cancer diagnosis with ancestries associated with higher hereditary risk (i.e., Ashkenazi Jewish descent) or a family history meeting the following criteria²:

≥ One close blood relative with ANY:

• Breast cancer at age ≤50
• Male breast cancer
• Ovarian cancer
• Pancreatic cancer
• Metastatic, node-positive, or very high risk or high-risk prostate cancer

≥ Three close blood relatives with prostate cancer (any grade) and/or breast cancer on the same side of the family including the patient with prostate cancer

Both NCCN and ASCO’s 2025 guidelines emphasize that both germline and tumor genomic testing are essential for all patients with metastatic prostate cancer. ASCO’s expert panel highlights that germline testing captures inherited mutations (often with implications for the patient’s family), while somatic testing can uncover tumor-specific alterations that directly inform treatment, especially in the metastatic setting.³

Together, these recommendations signal a shift in practice patterns: genetic testing is no longer reactive, it’s proactive. By expanding eligibility and embedding testing earlier in standard care pathways, patients and clinicians can have expanded discussions regarding treatment options and greater peace of mind when making treatment decisions.

Germline vs. Tumor Genomic (Somatic Testing): Do I Need Both?

Germline mutations are inherited and present in every cell of the body, while somatic mutations are acquired changes that occur only in the tumor. Both types of mutations can influence treatment decisions, but germline testing offers the added benefit of identifying inherited cancer risk, which opens the door to targeted therapies and informing care for the patient’s family.

Far from being just “nice-to-have” information, Dr. Jonathan Nowak of Brigham and Women’s Hospital noted in an interview with College of American Pathologist’s publication CAP Today, “many physicians don’t naturally think of performing germline testing to guide cancer therapy even though germline alterations in roughly 20 genes can impact such therapy.”⁴

In 2024, ASCO reinforced that both germline and somatic testing are essential, particularly for patients with metastatic disease. Together, they form a more complete and actionable profile that informs not only treatment decisions and family risk assessment, but also of eligibility for newly approved therapies and clinical trial access.

BRCA, Homologous Recombination Repair (HRR), and Beyond: What Mutations Mean for Treatment

As germline and tumor genomic testing become foundational in prostate cancer care, the presence, or absence, of certain mutations is what makes the results clinically actionable.

Among the most significant are mutations in BRCA1 and BRCA2, particularly BRCA2, which is not only the most commonly mutated gene in metastatic prostate cancer but also associated with more aggressive disease and poorer prognosis⁵. Patients with BRCA2 mutations and metastatic prostate cancer are eligible for PARP inhibitors, which have been shown to delay disease progression and, in some cases, improve survival when used early.

Beyond BRCA, alterations in other homologous recombination repair (HRR) genes, such as ATM, PALB2, CHEK2, and CDK12, can also influence treatment decisions. While these mutations are less common, they carry therapeutic relevance on their own. Additional tumor biomarkers, like microsatellite instability (MSI) and tumor mutational burden (TMB), offer separate insights that may further inform treatment, especially in advanced cases or when the disease is no longer responding to standard treatments. Many of these biomarkers are available through comprehensive genomic panels, such as those offered by Myriad Oncology^™.

In 2025, multiple FDA-approved PARP inhibitor combinations including olaparib + abiraterone⁶, talazoparib + enzalutamide⁷, and niraparib + abiraterone⁸ were added to the front-line treatment landscape for mCRPC patients with BRCA or HRR mutations. These therapies are no longer reserved for later lines of treatment. For patients who receive only one opportunity for systemic therapy, a group that includes up to 50% of men with mCRPC⁹, early access to matched therapies can mean the difference between months and years.

Identifying these mutations at diagnosis or progression doesn’t just expand treatment options, it can influence the timing of specific treatments. In many cases, it ensures patients are eligible for the right therapy while they’re still well enough to receive it.

Genetic Testing in Practice: A Workflow for Urology and Radiation Oncology Teams

Even as guidelines expand and new therapies emerge, one of the most common questions from clinicians remains: How do I integrate genetic testing into my practice without disrupting clinic flow?

The answer starts with a clear workflow. For high-risk or metastatic patients, testing should be initiated early, ideally at diagnosis or at the start of treatment planning. This way, results are available when they most meaningfully inform care.

To streamline this, many practices now rely on a single testing partner that can provide both germline and tumor genomic results, minimizing coordination and avoiding delays. Myriad Oncology, for example, offers the MyRisk^® Hereditary Cancer Test and the Precise^™ Tumor Molecular Tumor Profile Test for comprehensive tumor profiling, including key biomarkers like PDL1, ATM, HRR mutations, MSI, and TMB.

For patients who present earlier in their disease course, testing may still be appropriate based on guidelines. Partnering with labs that offer integrated support, such as Myriad Oncology^™’s patient education, can further ease the workflow burden for busy clinical teams.

Ultimately, genetic testing is not an add-on, it’s a clinical enabler. And when built into the workflow thoughtfully, it becomes a seamless part of delivering personalized, evidence-based care. In the end, genetic testing allows clinicians to have added individualized tools when sitting across from a patient in an exam room to assist with answering the question “what would you do if you were in my situation?”

References:

1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate V1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 20, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org.
2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V1.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed August 20, 2025. Content referenced from page MS-6. To view the most recent and complete version of the guideline, go online to NCCN.org.
3. ASCO Expert Panel. 2025. Selection of Germline Genetic Testing Panels in Patients with Cancer: Recommendations from the ASCO Expert Panel. American Society of Clinical Oncology. https://www.asco.org.
4. https://www.captodayonline.com/room-to-grow-tumor-germline-sequencing/
5. BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype Fettke, Heidi et al. eBioMedicine, Volume 95, 104738
6. DA Approves LYNPARZA® (olaparib) Plus Abiraterone and Prednisone or Prednisolone for Treatment of Adult Patients With BRCA-Mutated Metastatic Castration-ResistantProstateCancer (mCRPC) – Merck.com. (2023, July 18). Merck.com. https://www.merck.com/news/fda-approves-lynparza-olaparibplus-abiraterone-and-prednisone-or-prednisolone-for-treatment-of-adult-patients-with-brca-mutated-metastatic-castration-resistant-prostate-cancer-mcrpc/
7. DA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. U.S. Food And Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-enzalutamide-hrr-gene-mutated-metastatic-castration-resistant-prostate
8. Seymour, C. (2023, August 11). FDA approves Niraparib plus abiraterone acetate for BRCA+ MCRPC. OncLive. https://www.onclive.com/view/fda-approves-niraparib-plus-abiraterone- acetate-for-mcrpc
9. Shore ND, Laliberté F, Ionescu-Ittu R, Yang L, Mahendran M, Lejeune D, Yu LH, Burgents J, Duh MS, Ghate SR. Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors. Adv Ther. 2021 Aug;38(8): 4520-4540. doi: 10.1007/s12325-021-01823-6. Epub 2021 Jul 19. PMID: 34282527; PM