Molecular Testing's Role in Prostate Cancer Treatment
- It’s ver important that we have molecular testing available for metastatic prostate cancer.
- Some new treatments are based on having molecular testing: some mutations could make your cancer potentially susceptible and more responsive to PARP inhibitors.
- Targeted therapies focus on specific aspects found on cancer cells only (as opposed to chemotherapy, which can damage healthy cells in the process of fighting cancer).
- Next-Generation Sequencing (NGS) is a type of molecular testing that can provide information about any alterations or mutations in your tumor that may make a targeted therapy more likely to work (or not work).
SurvivorNet has put together this piece thinking of you, who live in the D.C. Metro area.Read More
- Your treatment options & whether you’re likely to benefit from a targeted therapy
- Whether the targeted therapy is likely to increase survival and improve quality of life
- Whether your cancer will likely become resistant to a targeted therapy
A targeted therapy is a kind of cancer treatment that focuses on specific aspects found on cancer cells only. This often leads to better activity against the tumor and fewer side effects compared with traditional chemotherapy.
For those residing in the DMV region, Dr. Madan is available to assist you or a loved one in comprehending the significance of these tests.
Next-Generation Sequencing (NGS) is a type of molecular testing. It is a comprehensive panel that looks for alterations or mutations in your tumor.
It’s like a modern toolbox used by scientists to quickly and affordably read the instructions of an organism’s DNA or RNA. This has helped researchers read a lot of genetic information fast, like reading a whole book, so they can understand entire sets of genes, find differences in genes, and study how genes work in a really big way.
To collect a sample for testing, your doctor will use part of your tumor tissue or do a small blood draw. Tumor-specific testing like this is called somatic testing.
Which Mutations Matter for Prostate Cancer?
Current national guidelines recommend that anybody diagnosed with metastatic prostate cancer should undergo genetic testing. Those with node positive disease or high risk prostate cancer may also benefit.
DNA damage is an ongoing occurrence that necessitates a sophisticated web of repair mechanisms to uphold the integrity of the genome.
In healthy cells, DNA may sometimes act strangely. When that happens, DNA is repaired via several mechanisms including the homologous recombination repair (HRR) pathway. In the presence of HRR gene mutations (HRRm), cells are unable to effectively repair broken DNA — and that could lead to cancer.
The most well-known of these homologous recombination repair genes are called BRCA1 and BRCA2.
“For cancers of the prostate, we are utilizing germline BRCA1 and BRCA2 testing. In stage four prostate cancers with those mutations can be treated with a PARP inhibitor.” – adds Dr Madan.
There are specific therapies (PARP inhibitors) for patients with BRCA mutations:
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 targets 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.
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.
Another genetic test we do for prostate cancer is checking for homologous recombination repair gene deficiency (HRD) for which a different PARP inhibitor (talazoparib) in addition to enzalutamide is used.
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).
After a diagnosis, it’s crucial to speak to your doctor about genetic testing and if it is necessary/could be helpful for your individual case.
The importance of genetic testing
Everybody who’s getting diagnosed with metastatic prostate cancer should talk to their doctors about getting genetic testing.
Unfortunately, many people being treated in smaller hospitals and cancer centers in their own communities are not getting tested for DNA repair gene alterations, and that could be because of a lack of resources or a lack of awareness.
Testing tumors for specific genetic changes is important for two reasons. First, as more targeted drugs enter the market, it is increasingly possible to target the specific alterations that drive someone’s tumor. And second, some of these genetic alterations, known as germline alterations, are associated with familial predisposition to the disease, which may prompt screening in other family members.
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.
Being a Washington DC resident dealing with prostate cancer brings specific questions and concerns. Where can you find the best medical facilities in the DMV area? How does the urban lifestyle affect treatment and recovery? MedStar Health in Washington, D.C., could be an option for you.
You should ask your healthcare team if the brand of molecular testing they are doing is optimal for your cancer type.
Questions To Ask Your Doctor:
- Am I a good candidate for next-generation sequencing?
- What are my chances of having a mutation that has a targetable drug?
- How long will it take to get my NGS testing results?
- Do you need a second biopsy to get more samples?
- Is there a clinical trial that is available for me?
- Is there any indication for NGS testing in early-stage prostate cancer?