Since Tom was diagnosed in 2015, the landscape has expanded for prostate cancer (PCa) diagnostics. Cancer treatments continue to advance. What this means to the patient is having targeted treatments with the ability to kill cancerous cells, while minimizing the damage to surrounding tissue. Treatments must try to exploit features that are unique to cancer cells, such as a specific protein that, like prostate-specific membrane antigen, is expressed on the cancer cell surface.

There has been a paradigm shift in treating cancers based on the genomic code of the tumor. What this means to the patient is that researchers can identify key genetic mutations associated with disease progression and tailor treatments accordingly.

What’s exciting to us is that research and clinical trials mean that our knowledge base is expanding all the time. What this means to the patient is that new therapies have brought the field closer to the goal of being able to implement precision oncology therapy for every patient.

Existing genomic technologies can “read” and interpret DNA (the molecule that carries genetic information for the development and functioning of an organism) to map unique cancer mutations and match these to precision medicines, which target the mutations in the cancer.

Right now, all men with localized high-risk, recurrent, or advanced disease should discuss germline testing. This test analyzes noncancer cells (like blood samples) to look for mutations that were inherited and are present in every cell of the body since birth. Also, patients with strong family history should be considered for testing, since the testing can help diagnose hereditary cancer predisposition syndrome and provide information about a patient’s likelihood of a future cancer diagnosis.

By contrast, somatic testing analyzes cancer cells to look for alterations in the genes of the tumor that have occurred over time. Currently, somatic testing is indicated for patients with metastatic PCa since the results can help identify those patients who might benefit from other therapies, such as targeted therapies or immunotherapies.

Patient advocacy groups such as ZERO Prostate Cancer encourage patients to get care adherent to National Comprehensive Cancer Network and AUA guidelines. ZERO educates patients on when they should be tested so they can talk with their doctors. An educated patient is an empowered patient. Ideally, patients who meet National Comprehensive Cancer Network criteria should get genetic counseling.

Education on genetic testing should include both germline and somatic testing (Figure 1), both before and after genetic testing. Often, specialized counseling needs to be considered, especially in the cases of positive germline alterations. For such cases, a genetic counselor can play an important role in the pre- and posttest education as well as in possible cascade testing where family members are also tested to rule out hereditary syndromes.

Figure 1. Education on genetic testing should include both germline and somatic testing, both before and after genetic testing. Reprinted with permission from ZERO.

Molecular profiling via somatic testing at the time of metastatic disease can help with more personalized therapy, leading to better outcomes. Biomarker testing for mutations associated with HRR (homologous recombination repair pathway), such as BRCA1 and 2 or ATM, plays an important role. These genetic markers help in the understanding of the individual profile, which influences both prognosis and treatment strategies, including more targeted treatments. In general, the preferred method is testing the available tumor tissue from a biopsy or surgery. However, when tumor tissue is not available, a liquid biopsy (which finds circulating tumor DNA) can be considered.

The process of comprehensive testing including both germline and somatic testing is complex and requires additional resources (Figure 2). Often, these tests are not conducted at the institutions where patients received their care, and the samples are sent out to external genetic companies to analyze the samples. For example, at University Hospitals Seidman Cancer Center and many other institutions there is a multidisciplinary team, including a genetic test assistant, that can help in this process. Currently, less than 50% of patients with PCa are offered genetic testing due to several barriers^1-3:

Figure 2. Genetic testing model at genitourinary (GU) clinics at University Hospitals Seidman Cancer Center. FTE indicates full-time equivalent. Courtesy of Pedro Barata, MD, MSc, FACP.

• Cost-effectiveness of genetic testing and shortage of genetic clinics especially in low- and middle-income countries
• Availability of genetic counseling for patients with advanced PCa in the early stages after diagnosis
• Limited genetic panels such as BRCA (breast cancer gene) and ATM (ataxia-telangiectasia mutated gene) panels only
• Challenges in sample selection: blood vs tumor vs circulating DNA
• Tissue availability

What This Means to the Patient

Genetic mutations in the DNA of cancer cells can help detect aggressive cancer subtypes, determine the progression of the disease, and manage the PCa more effectively.

Unmet Needs

• Define your risk
• Determine if you can pass it on
• Somatic testing may determine how the tumor was developed and identify the molecular makeup of the tumor, which can provide access to specific targeted therapies that otherwise would not be considered
• Avoid certain treatments
• Better prognostic information about the tumor
• Trust

The inclusion of genetic testing and counseling for HRR mutations will be critical for improving patient outcomes with advanced PCa.⁴

Takeaways

Clinicians should discuss treatment options with patients with advanced PCa based on life expectancy, comorbidities, preferences, and tumor characteristics.

Clinicians should encourage engagement with professional or community-based resources, including patient advocacy groups.

The opportunity of genetic testing should be considered and discussed with patients diagnosed with PCa, especially those diagnosed with high-risk, recurrent, or metastatic disease.

Genetic alterations such as mutations in the DNA of cancer cells can help define prognosis and predict response to targeted therapies, thus impacting the management of PCa more effectively.