Prostate Cancer | Genetic Testing
How you may be missing care opportunities for your prostate cancer patients
Invitae looks at how you may be missing important genetic insights for your prostate cancer patients
Prostate cancer affects millions of individuals worldwide.¹ But routine preventive options can help patients navigate care before a late-stage diagnosis.
Invitae shares how healthcare providers can use crucial genetic insights to inform care for their prostate cancer patients.
Understanding the genetics of prostate cancer
All cancers stem from genetic variants, broadly classified into two categories: acquired (called “somatic”) and inherited (called “germline”).
Acquired variants are genetic alterations that occur after conception and throughout our lives (typically due to exposure to various environmental factors or chance leading to the accumulation of variants over time). These variants cannot be passed down to future generations as they are present only in the affected individual’s cells. In prostate cancer, acquired genetic variants play a critical role in the malignant transformation of prostate cells, leading to cancer development.
Germline variants are the hereditary form of a gene alteration. These variants are typically in all body cells, including eggs or sperm, and are, therefore, capable of being passed on to offspring. They may contribute to a patient’s genetic predisposition to prostate cancer, making it more likely for it to occur in patients at an earlier age.
Restrictive criteria and missed opportunities in prostate cancer
Recent developments in research and guidelines have emphasized the need for a more inclusive approach to genetic testing in prostate cancer. Current guidelines for prostate cancer patients are too restrictive, only recommending hereditary cancer genetic testing for a subset of patients who meet specific high-risk criteria.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic recommend hereditary cancer genetic testing for patients with advanced/metastatic prostate cancer, which can impact targeted therapy selection and clinical trial options.³ These expanded guidelines, endorsed by multiple professional societies, recognize the importance of genetic testing in guiding care decisions and improving patient outcomes.
The NCCN Guidelines® for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic also recommend genetic testing based on testing criteria for men with a family history suggestive of a hereditary cancer predisposition and prostate cancer across the stage and risk spectrum. There are recommendations for testing unaffected men with an increased risk of being carriers of a variant associated with a high risk of developing prostate cancer based on their family history and/or ancestry, aiming to identify genetic cancer risk before cancer manifests.³
The existing approach to hereditary cancer genetic testing for prostate cancer relies on specific high-risk criteria, often resulting in missed opportunities for patients to receive essential genetic-informed care. Research has revealed the limitations of these restrictive guidelines, prompting a call for a paradigm shift in identifying and supporting individuals who could benefit from early detection and preventive measures.
A recent study unveiled a concerning trend: Nearly half of the individuals carrying disease-causing genetic variants would be missed by strictly following the existing guidelines.⁴ This highlights the urgency to reassess and broaden the criteria for genetic testing to ensure more patients have access to potentially life-changing information.
The consequences of relying on restrictive criteria are significant when missing crucial opportunities for early detection, risk assessment, and implementation of preventive strategies. Timely detection of these variants is vital as it can guide clinical decision-making, inform treatment options, and enable targeted interventions, working to improve patient outcomes.
The impact also extends beyond individuals directly affected by prostate cancer. Identifying inherited gene variants in patients can also have implications for their families. Genetic testing can provide essential information about inherited risk factors, allowing relatives to take proactive measures such as regular screenings, lifestyle modifications, or risk-reducing surgeries to mitigate their chances of developing the disease.
By embracing a more comprehensive approach, healthcare providers can identify individuals who may not meet the strict criteria but still carry genetic risk factors.
The following sections explore the potential benefits and implications of this more inclusive approach to hereditary genetic testing in prostate cancer.
Implications for medical management and precision therapies
Integrating genetic testing into the medical management of prostate cancer patients can support personalized care and precision therapies. Identifying hereditary cancer predisposition genes through genetic testing holds important implications for medical management, not only for the patients themselves but also for their families.
By understanding the specific genetic alterations driving an individual’s prostate cancer, healthcare providers can make informed decisions about potential next steps. Management options may include more frequent screenings, specialized surveillance protocols, or prophylactic interventions in high-risk individuals.
Variants in certain genes have been associated with increased responsiveness to particular treatments. Specific genetic testing may be available to help guide therapy decisions, such as the appropriateness of PARP inhibitors or platinum-based chemotherapeutics.⁵ healthcare providers can personalize care plans and help select more adequate therapies by identifying these variants, optimizing patient response and overall outcome.
In addition to care optimization, genetic testing can provide valuable prognostic information. Some genetic variants have been linked to more aggressive forms of prostate cancer or a higher risk for other cancers.⁵ Identifying these variants through genetic testing allows healthcare providers to stratify patients into different risk categories, enabling them to tailor surveillance and care plans accordingly.
Genetic testing can support patients at higher risk to receive more intensive interventions and close monitoring.
Screening and early detection for prostate cancer
Several guidelines have been established to guide healthcare professionals in determining the appropriate screening strategies for such individuals.
One high-risk cancer predisposition syndrome that includes prostate cancer is Hereditary Breast and Ovarian Cancer Syndrome (HBOC), caused by variants in the BRCA1/BRCA2 genes. These genes are more commonly known for their association with breast and ovarian cancers. However, they have also been linked to an increased risk of prostate cancer.⁵
Therefore, individuals with BRCA1 or BRCA2 disease-causing (pathogenic) variants may undergo prostate-specific antigen (PSA) screening at an earlier age than the general population.⁵ Individuals with a positive BRCA2 variant are recommended, and individuals with a positive BRCA1 variant can consider starting regular PSA screening at age 40.⁵
Patients with disease-causing variants in the BRCA2 gene warrant earlier screening, which is distinct from patients with BRCA1 variants who have a lower risk for prostate cancer than individuals with BRCA2 variants.⁵
Additionally, research highlights the importance of considering variants in the HOXB13, DNA mismatch repair (MMR), and ATM genes.⁵ These variants have been associated with an elevated risk of prostate cancer and can be considered when determining the appropriate age to initiate screening.⁵
Following a genetic test result, you can consider the following treatment approaches for your prostate cancer patients:
Active surveillance
Active surveillance plays a vital role in early-stage prostate cancer. Men with hereditary BRCA1, BRCA2, and ATM variants have been reported to have higher rates of upgraded biopsies while on active surveillance and more aggressive disease.⁶
Precision therapies
Genetic testing can inform treatment decision-making for chemotherapy, targeted therapy such as PARP inhibitors, and immune checkpoint inhibitors such as pembrolizumab. Studies have shown that patients with metastatic or advanced prostate cancer harboring inherited or acquired variants in DNA repair genes, such as BRCA1/BRCA2, ATM, PALB2, FANCA, RAD51D, and CHEK2, can benefit from PARP inhibitors and platinum-based chemotherapies based on improved progression-free and overall survival data.⁵
The currently approved or under-investigation PARP inhibitors for the treatment of prostate cancer include⁵:
- Olaparib
- Rucaparib
- Niraparib
- Talazoparib
- Veliparib
Precision therapies guided by genetic testing offer these and other targeted treatment options, potentially improving outcomes for prostate cancer patients with specific genetic variants.
Navigating the spectrum of genetic testing options for prostate cancer
Genetic testing options can include small/focused, guidelines-focused, cancer-specific, or broad pan-cancer panels. Each offers different levels of genetic information, allowing you to choose the most appropriate testing approach based on the patient’s clinical presentation, family history, and risk factors.
Reflex panels can also provide a step-wise approach to testing. In reflex panels, testing is initially performed on a smaller set of genes. If the results return without detecting disease-causing variants, a larger set of genes can be tested on the same sample at no additional charge. This approach helps promote thorough evaluation while remaining cost-effective.
Hereditary cancer genetic testing can use various sample sources, including blood, saliva, or buccal swabs. Either option provides reliable DNA for analysis, allowing for an accurate assessment of hereditary cancer genes.
By incorporating these testing options and approaches into your practice, you can expand your ability to identify at-risk individuals, implement appropriate screening and surveillance strategies, and work to offer personalized interventions based on a patient’s genetic profile. You can provide precise, tailored care that improves patient outcomes and helps shape the future of prostate cancer management.
To learn more about genetic testing options for prostate cancer patients, visit Invitae’s website.
References
- Wang L, et al. Frontiers in Public Health. 2022;10.
- Samader NJ, et al. JAMA Oncol. 2021;7(2):230–237.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® ) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed February 13, 2023. 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. NCCN, National Comprehensive Cancer Network® (NCCN®).
- Shore N, et al. Eur Urol Oncol. 2023;S2588–9311(23)00150–5.
- Giri VN, et al. CA: A Cancer Journal for Clinicians. 2022;72(4):360–371.
- Carter HB, et al. Eur Urol. 2019;75(5):743–749.
