Blogs

Completing the Picture: How Combining Germline Testing with Tumor Expression Testing Enhances Prostate Cancer Management

When caring for prostate cancer patients, doctors face the critical decision of which tests to order for optimal disease management. While tumor expression testing remains a cornerstone in cancer diagnosis and treatment planning, adding germline testing to the diagnostic toolbox may offer a more comprehensive understanding of a patient’s condition.

To understand how combining these tests can provide a more comprehensive picture and enhance cancer management, let's follow the case of Mike, a 55-year-old man recently diagnosed with prostate cancer.

Standard tumor expression testing analyzes the genetic makeup of tumor cells, providing information about the cancer's behavior and potential treatment responses.1 In Mike’s case, tumor expression testing shows that his cancer appears to be low-risk, suggesting that active surveillance might be a sufficient course of action.

However, tumor expression testing has its limitations. While it offers valuable insights into the current state of the cancer, it doesn't provide information about inherited genetic risks or the potential for future cancer developments. This is where germline testing can fill in gaps.

Germline testing analyzes DNA to identify inherited genetic mutations, providing crucial insights for screening, prevention, and treatment management of prostate cancer. It enhances early detection, enables proactive risk reduction strategies, and guides personalized treatment plans based on genetic profiles. ProstateNow, offered by GoPath Diagnostics, is a comprehensive germline test that includes all known prostate cancer susceptibility genes and over 200 risk-associated variants, allowing for calculating Genetic Risk Scores (GRS) across multiple races.

In Mike's case, the germline test reveals that he carries a BRCA2 mutation, which is associated with more aggressive prostate cancers and a higher risk of progression. Suddenly, the picture of Mike's cancer risk has changed dramatically. Despite the initially reassuring tumor expression results, the germline test results might lead Mike's physician to recommend more aggressive treatment or closer monitoring.

ProstateNow is designed to detect Rare Pathogenic Mutations (RPMs) in 23 genes associated with prostate cancer risk and severity. For individuals with these mutations, like Mike, the risk of developing prostate cancer is approximately 2 to 8 times higher over their lifetime, depending on the specific gene affected. Some RPMs are linked to more aggressive forms of the disease and a higher risk of metastatic progression. This information provides Mike and his doctor with a more comprehensive understanding of his condition.

The Genetic Risk Score (GRS) calculated by ProstateNow offers another layer of insight. It provides an individual’s relative risk for prostate cancer compared to the general population. This score can be used to calculate Mike's remaining lifetime risk for prostate cancer, giving his doctor an easily interpreted absolute risk calculation. High GRS is associated with a higher likelihood of developing prostate cancer and may inform decisions regarding screening frequency and intensity.

But the benefits of germline testing extend beyond Mike. This information prompts genetic counseling for Mike's family members, who may also carry the BRCA2 mutation and benefit from increased cancer screening. GoPath Diagnostics works closely with genetic counseling services that can guide Mike and his family through the genetic testing process, providing the information, support, and resources needed to understand the risks and benefits of genetic testing and the interpretation of test results.

Furthermore, Mike's BRCA2 mutation may indicate sensitivity to specific treatments, such as PARP inhibitors, guiding treatment decisions in ways that tumor expression testing alone cannot. It can also reveal Mike's risk for other cancers, such as pancreatic cancer, which wouldn't be apparent from prostate tumor expression testing alone.

By combining the results of both tumor expression and germline testing, Mike's doctor can now create a personalized treatment plan. They can make more informed decisions about whether active surveillance is truly appropriate given Mike's genetic predisposition, or whether more aggressive treatment might be warranted despite the low-risk appearance of the current tumor.

As we continue to unravel the genetic complexities of prostate cancer, the integration of both tumor expression and germline testing modalities, such as the comprehensive ProstateNow panel, will become an essential component of high-quality, personalized cancer care. By embracing this integrated approach, doctors can visualize a more complete picture of prostate cancer risk and management, offering patients like Mike and his family the best possible care and outcomes.

Interested in incorporating ProstateNow into your cancer management toolkit?

Contact us at GoPath Diagnostics to find out how!

1. R I A, Shamsudeen S, Leslie SW. Prostate Cancer Tissue-Based Biomarkers. In: StatPearls. StatPearls Publishing; 2024. Accessed July 23, 2024. http://www.ncbi.nlm.nih.gov/books/NBK587345/