Genetic Mutations Matter in Prostate Cancer
- When diagnosed with prostate cancer, you can undergo several types of genetic testing, which help to better personalize your treatment and inform future decisions.
- The main types of genetic testing are germline testing which looks for inherited DNA mutations that can be passed down from parents, and somatic tumor testing, which looks at changes in the tumor DNA itself.
- Both germline and somatic testing have different indications. Somatic tumor testing is typically reserved for advanced or metastatic prostate cancer, while germline testing can be done in metastatic disease or if there is a significant personal or familial risk.
- Both forms of testing, when indicated, provide valuable information regardless of the results.
- With germline testing, negative results can give families peace of mind. Positive results can help inform families and allow them to protect themselves from potential cancer in the future. Positive germline results can also help tailor future treatments if you have metastatic disease.
- With somatic testing negative results, let your healthcare team know which future therapies are ineffective and can be avoided. Positive results can provide options for targeted therapies and potential enrollment in clinical trials.
Localized Prostate Cancer and Genetic Mutation Testing
If you present with a more localized disease that has not spread distantly, the treatment is more standardized, relying on various combinations of radiation, surgery, and hormone therapy. Because the treatments for localized disease are typically effective on prostate cancer regardless of the underlying genetics, there is often less of a need for genetic testing.
Metastatic Prostate Cancer and Genetic Mutation TestingRead More
Why is Genetic Tumor Testing Performed in Metastatic Prostate Cancer?The genetic testing performed on prostate cancer also called somatic tumor testing, analyzes the DNA of the cancer itself to identify mutations. DNA is the blueprint or code of a cell that tells it how to behave, grow, and respond to the surrounding environment. Normal cells have checkpoints and regulations in place to protect them from uncontrolled growth and spread. Cancer has bypassed these protections, and in the process of growing and dividing, the cells can develop several mutations or changes in the DNA.
Patients with metastatic prostate cancer that has spread to other sites in the body are more likely to have mutations in the DNA that can be identified with testing.
So You Have Metastatic Prostate Cancer – How Is Genetic Tumor Testing Performed?
You typically need a piece of tissue from a biopsy to test for these DNA mutations in the cancer cells. If genetic testing is being performed for the first time, tissue from your initial biopsy or prior surgery can often be used. Your healthcare team might also consider a biopsy of a metastatic site.
When doing genetic testing of the tumor, it is a national guideline to obtain tissue when possible. If this is unsafe or unfeasible, a liquid biopsy, or molecular testing of the blood looking for circulating tumor DNA (ctDNA), can be obtained.
Rapid changes in the testing performed for tumor genetics as well as the available clinical trials in progress, make it difficult to recommend specific testing. If you have metastatic prostate cancer and have not been offered genetic testing, please ask your healthcare team about current testing options available.
When Do You Need to Get Genetic Tumor Testing?
Hormone Sensitive Metastatic Disease
When a patient presents with metastatic prostate cancer, a majority of patients are hormone-sensitive. This means that there are a variety of medications available, called hormone therapy or androgen deprivation therapy (ADT), that can be used to treat metastatic disease, usually by decreasing the level of testosterone. Testosterone can stimulate prostate cancer cells to grow and spread. Hormone therapy (or ADT) works on most prostate cancers regardless of the specific genetic mutations. The targeted therapies that require genetic mutation testing of the tumor typically come after hormone therapy has stopped working.
Because hormone therapy is typically used first and can be an effective therapy for an extended period of time, there is often no immediate rush to get the testing done, although it is important to perform the testing when you can. “So we do have a little bit of time with an individual presenting with newly diagnosed metastatic disease. It’s never too early to know, and yet the information that we have may not be used until a later state” says Dr. Michael Carducci, a medical oncologist at Johns Hopkins with a focus on prostate cancer research.
Hormone Resistant Metastatic Disease
If a patient presents with metastatic prostate cancer but it is already resistant to hormone therapy, it is called metastatic castrate-resistant prostate cancer (mCRPC). In this setting, it is more important to get the genetic testing of the tumor done as soon as possible. “And so it’s more important to know at that time what the status of their tumor mutation is as well as the genes that they were born with.” Says Dr. Carducci.
The tumor genetics can change over the course of various therapies, and re-evaluation with repeat biopsy can be considered at the time of disease progression or when resistance to ongoing therapy has developed to further inform treatment decisions.
Specific indications for genetic tumor testing:
- Any metastatic prostate cancer should test for BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12 (can be considered if you have the disease with lymph nodes involved)
- Metastatic prostate cancer, which has become resistant to hormone therapy, should test for: MSI-H or dMMR (can be considered if you have the disease with lymph nodes involved or metastatic disease sensitive to hormone therapy)
What About Testing for Inherited (Germline) Genetic Mutations?
Some patients with prostate cancer are at risk for carrying inherited genetic mutations, increasing their risk of developing specific cancers. These inherited or germline mutations can be passed from generation to generation.
Germline testing, or testing for inherited genetic mutations, is not indicated for all patients diagnosed with prostate cancer. Only 5-10% of all prostate cancers have an associated germline mutation or inherited cancer-causing gene.
When to test for Inherited (Germline) Mutations?
Germline testing is not indicated for all patients diagnosed with prostate cancer. Only 5-10% of all prostate cancers have an associated germline mutation or inherited cancer-causing gene. There are specific personal factors, family history, and traits of the prostate cancer disease itself that are more likely to be associated with an inherited genetic mutation.
In your prostate cancer workup, if you meet these criteria or there is a concern from your healthcare team, you will often be referred for genetic counseling. In consultation with a genetic specialist, you will typically be asked a more extensive list of questions to see if you qualify for germline genetic testing.
If you are diagnosed with prostate cancer, indications for germline testing include:
- Metastatic prostate cancer
- Lymph node-positive prostate cancer, or localized disease that is considered high-risk or very-high-risk
- Personal history of breast cancer
- Ashkenazi Jewish ancestry
- Personal history of pancreatic, colorectal, gastric, melanoma, upper tract urothelial, glioblastoma, biliary tract, or small intestinal cancer
- Known family history of inherited cancer mutations
- A strong family history of certain cancers, especially if diagnosed at a young age, including breast, colorectal, endometrial, ovarian, pancreatic, and prostate cancer
When Do the Results of Genetic Testing Matter?
When inherited (germline) or tumor (somatic) genetic testing is indicated, the results always provide valuable information. The indications for both tests are different, and the information gathered from both tests also has different implications regarding your disease and next steps.
Negative Germline Testing
This means that there was no clear inherited cancer-causing gene identified. This result can give your family peace of mind that they do not carry an inherited cancer-causing gene. Despite this, some prostate cancers are familial, meaning that prostate cancer has developed in multiple family members, but it is not related to any specific cancer-causing gene. It is important to be aware of your family history of cancer.
Positive Germline Testing
If positive, it means a specific inherited cancer-causing gene was identified. Common inherited genes include BRCA 1, BRCA 2, ATM, and CHEK2, among others.
A positive result can allow other families to test themselves for the inherited genetic mutation. If the family also has a positive result and no current diagnosis of cancer, depending on the inherited genetic mutation identified, it can allow the family to take the appropriate steps for early screening and detection of potential cancers.
Certain inherited genetic mutations can also be targeted by specific cancer treatments in the setting of metastatic disease if hormone therapy is not working or is not an option.
Negative Somatic Tumor Testing
80% of the time, tumor testing for genetic mutations in metastatic prostate cancer is negative. Although negative, we can “make sure that we don’t give you drugs that are not likely to help you because you don’t have the mutations,” says Dr. Carducci. There are still options for treatment. However, we can avoid the ones that don’t work in this situation.
Positive Somatic Tumor Testing
Approximately 20% of patients with metastatic prostate cancer have a specific, actionable mutation. This means that the DNA mutation present in the tumor can then be specifically targeted with treatment. Depending on the mutation identified and where you are receiving your cancer care, you can also be a candidate for enrollment in ongoing clinical trials.