New Genetic Testing Recommendations Could Improve Early Detection in Prostate Cancer

Recent changes to the National Comprehensive Cancer Network (NCCN) guidelines around prostate cancer have updated the indications for genetic testing and have opened up a broader discussion on how it can be used to improve prostate cancer detection and treatment, according to Dr. James Mohler.
BY Jessica Skarzynski
PUBLISHED October 20, 2019
Recent changes to the National Comprehensive Cancer Network (NCCN) guidelines around prostate cancer have updated the indications for genetic testing and have opened up a broader discussion on how it can be used to improve prostate cancer detection and treatment, according to Dr. James Mohler.

In an interview with OncLive®, CURE®’s sister publication, Mohler, the associate director and senior vice president of translational research at Roswell Park Comprehensive Cancer Center, explained the rationale behind these updates and went into greater detail on what factors to consider when looking into whether genetic testing is right for you.

CURE®: Can you give an overview of the changes discussed at the conference?
Mohler: The NCCN guidelines were delayed last year from their normal release in November until March, this largely was due to the fact that we improved the indications for genetic testing, (including) how to perform those tests and how to utilize the information. And we did that both in the localized prostate cancer situation, as well as for advanced disease, where the situations are quite different. In one we’re talking about genomic testing, the other we’re talking about somatic testing.

We made so many changes that we also thought we should explain it. So, we published an article in JNCCN (the Journal of the National Comprehensive Cancer Network), and then we’re also participating in this meeting to present the reasons for our changes and also to gain insight from the experts at this meeting on how we can improve further.

My presentation focused on the changes we made, but most importantly, I talked about what we can do better, because of the rapidly emerging data on genetic testing abnormalities, both as they pertain to prostate cancer early detection, to risk assessment, to cascade testing and finally to the treatment of prostate cancer.

Could you provide more details about the changes that were made?
One of the most important things (to note) is that it’s never been really clear on what a family history should consist of when you’re addressing a man with prostate cancer. Too often, our family history is recorded, for instance, in an EHR (electronic health record) as positive or negative, or it might even say what relative had cancer. But it doesn’t often capture the age of diagnosis, treatment received, whether they developed or presented with metastatic disease, or most importantly, if they died of it.

So we prescribed what a family history should be, as well as other things, in addition to the diagnoses of prostate cancer, that should be captured: other hereditary syndromes, whether they are Ashkenazi Jewish or not, or whether they have known mutations in their families, because many families are having genetic testing now and there are a lot more families who know what runs in their family. Then of course, whether they’re African American or not, and most importantly, if they have family members with prostate cancer, where are they in the family tree. All of this was made so it could be routinized in clinical practice, so we could do a better job of capturing family history.

The next thing we did was try and specify the minimum number of genes that should be assayed for mutations in the situation of a positive family history, whether the man was having a tumor already diagnosed sequenced, or whether one had failed androgen-deprivation therapy and was having a metastatic site biopsied and sequenced.

Finally, we, as always, called for more clinical trials to determine whether they are taking action based on new genetic testing information actually impacts outcome, which really is the important question that remains in many cases not yet known.

What are the main factors to determine whether someone should be genetically tested?
I think that right now, if you have a strong family history of prostate cancer, especially when diagnosed at an early age, which I would consider under age 55, and metastatic or then became fatal to that individual, that really raises the question of whether you have a DNA-repair gene abnormality in your family.

If you have a regional or metastatic prostate cancer especially at a young age, that really raises the question of whether you have, in that tumor, a mutation that’s affecting the aggressiveness that it presented at, and more importantly, (if it) could be a potential target for new therapies.

Once you’ve failed conventional therapy for advanced disease, I think anyone with an accessible lesion right now warrants a biopsy to see if you can do a better job of selecting what their tertiary or quaternary treatment should be.
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