When to Get Testing with Metastatic Prostate Cancer
- Testing for inherited cancer-causing genes (germline testing) and genetic mutations of the prostate cancer itself (somatic tumor testing) have specific indications that vary based on several factors.
- Germline testing is indicated for anybody with metastatic prostate cancer, high-risk disease confined to the prostate or surrounding area, a strong personal history of certain cancers, or a strong family history of certain cancers, among other factors.
- Somatic tumor testing is typically reserved for patients with regional (lymph nodes involved) or metastatic disease.
- Somatic testing helps determine if patients are candidates for future targeted treatments or enrollment into ongoing clinical trials.
- Often there is no immediate need to obtain somatic tumor testing because first-line therapy for metastatic disease typically involves hormone therapy which is not specific to genetic changes.
- Somatic testing is important information to gather to help plan for the next steps if your metastatic prostate cancer becomes resistant to hormone therapy or you are unable to undergo hormone therapy.
- If you feel you are a candidate for germline or somatic testing for prostate cancer but have not received testing, please consult with your healthcare team.
Prostate cancer can present in a variety of ways, and the disease course can vary significantly based on several factors, including the initial stage of disease at presentation, an individual’s health, available treatment options, and behavior and genetics of the cancer. Regardless of disease presentation, several pieces of information are gathered to better characterize the disease.
During the initial workup for either localized prostate cancer, which is confined to the prostate and surrounding tissues, or metastatic disease, which has spread to distant sites, it is part of national guidelines to obtain a tissue biopsy of the cancer, a personal history of the disease itself, a thorough family history, several lab tests such as the PSA, a physical exam, and imaging depending on the risk group of the disease.Read More
Germline TestingGermline mutation testing can potentially identify genes passed down to children from parents that predispose an individual to the development of cancers in specific organs depending on the specific genetic mutation. Germline testing is what most people commonly think about when they hear the word gene. Why? This is the type of gene or trait that can be passed on from one generation to the next. Germline testing uses normal cells in your body to identify a potential inherited mutation and is typically performed on saliva. It has several benefits. “Even in circumstances when there are no results, it helps provide some peace of mind for families,” says Dr. Michael Carducci, a medical oncologist at Johns Hopkins Kimmel Cancer Center who focuses on prostate cancer research. If positive, it can allow other family members 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.
When Should I Get Germline Testing?
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. Even if there is not a specific inherited mutation identified, there can still be a familial risk, meaning that prostate cancer has developed in multiple family members but it is not related to any specific cancer-causing gene.
There are specific personal factors, family history, and traits of prostate cancer itself that are more likely to be associated with an inherited genetic mutation.
During the initial workup and staging of your prostate cancer, if you meet specific 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
If there is any concern regarding your family history of cancer and you think you may be at risk of an inherited cancer gene, please consult with your healthcare team for further evaluation.
If your prostate cancer is metastatic, involves a lymph node, or is high-risk, and you have not been offered germline genetic testing, please consult your healthcare team.
Somatic Tumor Testing
Somatic mutation testing looks for changes in the DNA of the tumor itself. Somatic mutations are not inherited from parents and typically occur spontaneously in the cancer cells. This means these mutations are not passed on from generation to generation like germline mutations are. Testing often requires a piece of the cancer tissue, and if somatic testing is being performed for the first time, the initial biopsy of your prostate cancer that was obtained at the time of surgery or initial diagnosis can often be used.
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. When doing somatic tumor testing, national guidelines recommend obtaining a tissue sample directly from the tumor 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.
When Should I Get Somatic Tumor Testing?
When somatic tumor testing with next-generation sequencing is indicated, benefits include discovering potential targeted therapies, potential enrollment in ongoing clinical trials, and avoidance of treatments that are ineffective if no genetic mutation with targeted therapies is identified.
The indications for somatic tumor testing are less defined as compared to germline testing. However, testing is typically recommended for patients with metastatic prostate cancer.
Why Can’t I Get Somatic Tumor Testing in Early Stage Disease?
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. Somatic tumor testing would not change treatment recommendations in this setting.
If I Have Metastatic Prostate Cancer, How Quickly Do I Need to Get Somatic Tumor Testing?
Even on initial presentation with metastatic prostate cancer, first-line treatment typically consists of hormone therapy to control the disease. When hormone therapy has become ineffective, or the disease has become resistant to this treatment and new treatment options are needed, the information from somatic tumor testing and potential targeted therapies becomes more important.
Even if you are diagnosed with metastatic prostate cancer, which has spread distantly, getting somatic tumor testing is not an emergency or immediate requirement. It is important information to gather for future treatments, but you will typically not be delaying the initial recommended hormone therapy. If you are concerned that you need somatic tumor testing, please discuss this with your healthcare team.
Indications for molecular testing in metastatic prostate cancer
In general, indications include:
- In any metastatic prostate cancer, test for BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12. (Testing can be considered with lymph node-positive disease)
- In metastatic prostate cancer, which has become resistant to hormone therapy, test for MSI-H or dMMR (testing can be considered if you have the disease with lymph nodes involved or metastatic disease still sensitive to hormone therapy)
Rapid changes in the testing performed for somatic tumor testing as well as the available clinical trials in progress, make it difficult to recommend specific testing. Additionally, re-testing can be performed. “I recommend retesting in someone whose cancers changed in a different way or did something that’s somewhat unexpected,” says Dr. Carducci. Sometimes this can provide new answers and further guide therapy.
If you have metastatic prostate cancer and have not been offered testing, please ask your healthcare team about current testing options available.