Genetic Testing's Role in Prostate Cancer Treatment
- Precision medicine is an approach that tailors medical care to individual characteristics, such as genes and lifestyle, for more personalized treatment.
- Understanding cancer genetics can help diagnose, predict and treat cases of prostate cancer.
- Several mistakes in the DNA, such as BRCA mutations, may help fuel prostate tumor growth.
- Patients with metastatic prostate cancer (or cancer that has spread to distant parts of the body) should consider have genetic testing.
“Molecular testing really allows us to personalize that treatment and identify whether your cancer would be one that you could benefit from this type of treatment, or if not, if there is another treatment that would be a more effective option for you,” says Dr. Hannah McManus, a genitourinary oncologist at Duke Cancer Center Genitourinary Clinic.Read More
What is Next-Generation Sequencing?“So there’s a lot of terms and it can be confusing,” says Dr. McManus. Next-generation sequencing, or NGS, is the same as next-generation testing, comprehensive genomic profiling, broad molecular profiling or high-throughput sequencing. “NGS is a technique that’s used within molecular profiling. So it’s really one of the more common things that we use in molecular testing and cancer. This is genetic testing that lets us sequence the DNA. It’s fast and an efficient way to be able to profile someone’s cancer.”
NGS isn’t a particular test for a specific type of cancer. Instead, it’s a group of tests that search for all the genetic changes in a tumor’s genes.
Next-generation sequencing is a highly sophisticated approach that has transformed how genes are studied. Imagine it as a modern toolkit that scientists use to quickly interpret the DNA or RNA of an organism. Because of this new method, researchers can quickly get a lot of important genetic information, kind of like reading a whole book. This helps them understand all the genes, find differences in genes, and learn a lot more about how genes work.
What is DNA?
Imagine that DNA is like a recipe book for living things. Just like a recipe book contains instructions for cooking delicious meals, DNA contains instructions for building and running every living thing on Earth.
DNA stands for “deoxyribonucleic acid.” It’s a special code made up of four different “letters” A, T, C, and G:
- Adenine (A),
- Thymine (T)
- Cytosine (C)
- Guanine (G)
These letters are like the alphabet of life. They form long chains, just like sentences in a book. These chains are bundled up inside tiny structures called cells, which are like the kitchen of a living thing.
Every living creature, whether it’s a plant, an animal, or a person, has its own unique recipe book (DNA). This recipe book tells the cells how to do everything: from making your hair a certain color to helping your body fight off illnesses.
Prostate Cancer Driver Mutations
In normal cells, DNA occasionally encounters anomalies. In such instances, these aberrant DNA undergo repairs through several mechanisms including the homologous recombination repair (HRR) pathway.
If there are mutations in the homologous recombination repair genes (HRRm), cells lose the capacity to efficiently mend these damaged DNA strands, potentially resulting in the development of cancer.
The most famous of these Homologous recombination repair genes are called BRCA1 and BRCA2.
HRR gene mutations occur in approximately 25% of patients with advanced prostate cancer.
Up to 15% of men with metastatic and 10% of men with localized prostate cancer have mutations in homologous recombination repair (HRR) genes, such as BRCA2, BRCA1, ATM, CHEK2, PALB2, and mismatch repair (MMR) genes (MLH1, MSH2, PMS2 and MSH6).
Mutations in HRR genes can be hereditary (germline) or sporadic or nonhereditary (somatic).
Between 5% and 15% of prostate cancers are passed down in families, suggesting that it’s more likely to appear if other family members have had it. In men with certain inherited genetic changes, prostate cancer can be more aggressive than in those who don’t have these changes.
If a person’s dad, brother, or son had prostate cancer, his chances of getting it become two to three times higher. This chance gets even more likely if more family members had prostate, breast, or ovarian cancers. The age when a close family member got cancer matters, too.
Why Does Genetic Testing Matter?
For advanced prostate cancer patients, genetic testing not only provides clues as to how to treat the disease, but it may also reveal the cancer’s genetic tendency to behave in a certain way.
This means genetic testing may be critical way oncologists can tailor patients’ treatments in order to have the best results.
“We, actually have specific therapies called PARP inhibitors that can be approved options for patients with these [BRCA] mutations. And these are relatively common in prostate cancer mutations,” adds Dr. McManus.
Lynparza, a type of PARP inhibitor, is a treatment for men who have a form of advanced prostate cancer that is not responding to therapy with hormones. It selectively target and kills cancer cells associated with tumors that have defects in their ability to repair their DNA. This helps block prostate cancer growth.
Specifically, these men are classified as having metastatic castration-resistant prostate cancer (mCRPC).
Rubraca is another option for men with BRCA+ metastatic castration-resistant prostate cancer who have received certain cancer treatments.
“It’s really important that we have molecular testing available for cancer because these new treatments are based on having molecular testing showing that there is one of these BRCA mutations, that would make your cancer potentially susceptible and more responsive to this type of treatment,” says Dr. McManus.
In conclusion: every patient with metastatic prostate cancer should consider having genetic testing. This becomes more important if your cancer has stopped responding to hormonal therapy — a state known as castration-resistant prostate cancer.
How is Molecular Testing Performed?
“If you were to get NGS testing. It usually starts with a discussion with your oncologist, where we talk about ordering the test and why we would order it,” explains Dr. McManus.
The test can be done via the cancer tissue that’s obtained during biopsy or surgery. She explains that this is the most common way of analyzing the cancer mutations.
“Most patients have already had a biopsy or a sample taken of the tumor, when they come to see their oncologist. And that [tissue] can be used for NGS testing,” says Dr. McManus.
Another way to do the testing is via blood — where the test can pick up the cancer DNA in the blood and analyze it for gene changes. This is known as a Liquid Biopsy.
“Liquid biopsy is a term we use to do sort of genetic testing or a molecular profiling of someone’s cancer from a blood sample,” says Dr. McManus.
It’s a blood test that detects cancer cells or cancer DNA that are circulating in the blood. This DNA is also known as “circulating tumor DNA” or “ctDNA.”
Just like our body’s regular cells die and get replaced, cancer cells also go through this. When these cancer cells die, they break apart and are let go from the tumor into the bloodstream.
“[A Liquid biopsy is] looking for the cancer DNA in the bloodstream to send that into testing. (That is) other than having the (tumor) biopsy which maybe was already taken,” adds Dr. McManus.
“Usually that takes a couple weeks and then we get that testing back. So we can sit down and look at it together in clinic, and talk about the results and then talk about next steps of how that should impact the treatment decisions.”
PARP inhibitors side effects
Unfortunately, just like with all cancer treatments, PARP inhibitors have side effects. Whether you’ll experience major side effects from PARP inhibitors depends on different things, like which specific one you’re using, how much of it you take, and if you’re using it alone or with other treatments.
The most common side effects are:
- Nausea, vomiting (upset stomach)
- Decreased red blood cell count (anemia)
- Changes in liver function tests
- Decreased appetite
- Constipation or diarrhea
- Decreased platelet count
Some patients might find these side effects really hard to deal with, but doctors can usually help make them better or even make them go away.
Types of NGS Testing On The Market
There are a number of tests you may encounter, depending on where you are getting treatment and what you are getting treatment for. Here are some of the common ones currently on the market:
- FoundationOne®CDx looks at 324 genes in solid tumors and says it can takes up to 12 days for results. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions.
- OmniSeq Insight provides comprehensive genomic and immune profiling for all solid tumors. It looks for 523 different genes. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB), as well as PD-L1 by immunohistochemistry (IHC).
- Cobas EGFR Mutation Test v2 identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene. It is designed to test both tissue and plasma specimens with a single kit, and allows labs to run tissue and plasma on the same plate simultaneously.
You should ask your healthcare team if the brand of molecular testing they are doing is optimal for your cancer type.
Prostate Cancer Overview
Prostate cancer, the most prevalent cancer in men, originates in the prostate gland, resembling a walnut in shape, situated between the bladder and rectum. This gland produces the fluid vital for nourishing sperm. In the United States, screening tests largely detect prostate cancer. The behavior of this cancer can differ significantly from one individual to another.
According to expert physicians interviewed by SurvivorNet, being diagnosed with prostate cancer shouldn’t discourage hope. Numerous effective treatment options exist. In recent years, surgical and radiation advancements have mitigated treatment side effects, maintaining high cure rates. Even for those with advanced-stage cancer, innovative options promise effective treatment without compromising quality of life.
Questions to Ask Your Doctor
- How aggressively should my prostate cancer treatment be?
- Am I eligible to receive targeted therapy for prostate cancer? Am I more, or less, likely to respond to this treatment?
- Do I have any genetic mutation that would change the course of my treatment?
- How long does it take to get my NGS testing results?
- Do you need both the tissue sample and blood samples for NGS testing?
- Is there a clinical trial that would be relevant for me?