Meeting for those with genetic mutations

Really sorry I missed this, my husband has the ATM gene mutation. His father and sister both passed from pancreatic cancer and we were diligently tracking and monitoring for that particular type of cancer. He is in a study at Stanford to find an early bio-marker and is getting an MRI every other year and the other years he gets a endscopic ultrasound to look for signs of cancer.

The prostate cancer snuck up on us!!! He was diagnosed in late September - Gleason 9 T3bN0M0 and will begin treatment on Feb 3 with HDR Brachytherapy followed by 5 weeks of Proton Beam Therapy.

I'm really sorry I missed this event, was it recorded?

@wilkinson1ski
It was not recorded. Interesting thing was there was no one in the meeting with an ATM issue. There were multiple other mutations however.
There will be another meeting in April, it may be later than you would like, but you can probably ask some questions that can help you even then. You need to install GoTo Meeting in order to attend the meetings. The meeting named you Put into join is ancanschmier

April 9th at 8 pm Eastern
July 9th at 8 pm Eastern
October 8th at 8 pm Eastern

I have BRCA2 but somebody on this forum that that has ATM and lives in Russia asked me to ask questions for him. He has a very aggressive prostate cancer, at 46 with a lot of spread.

In his case, he has not been able to get his testosterone below 49 even though he’s been on ADT for 1.5 years. After chemo, Erleada and ADT he has a PSA of .04.

One of these big concerns is he has not had surgery or radiation on the prostate. Because of the spread of his cancer, they usually don’t do surgery, but as you’ll see below radiation is an issue.

I asked during the meeting and was told that you should be on an ADT antagonist to see if that will get your testosterone down.
You may have
Firmagon. (Degarelix) it is one, you have to get an injection in the stomach once a month.
Orgovyx (relugolix) is another. That is the new pill ADT. I doubt that’s available in Russia.
The drug you are on is an agonist, like Lupron and switching might make a difference.

You could ask the doctor there about it

Another discussion that came up with ATM is related to treating your prostate

As I mentioned, they usually don’t do prostate cancer surgery once your cancer has spread outside the prostate
There is however, a problem with giving radiation to the prostate. ATM apparently has some real problems with radiation, it can cause higher secondary cancer risk and many normal cells to die. They didn’t want to get into it too heavily in the meeting because it’s a very complex issue. This is something you might ask your doctor about and do some searching on the web to see what information you can come up with.

@wilkinson1ski
I am also with ATM mutation. From US but I live in Germany.
This month I will be doing a somatic testing to see if I have developed any other mutation on my own, especially since I did 11 years in the military.
I heard that there is PARP therapy for ATM mutation, however the opinions are split on the effectiveness of this therapy for ATM.
For me the 3 month-depot Lupron showed results in the 1st month, but as i checked my PSA and testosterone on month 2, It was rising back up quite fast (test. 4.3, PSA 11.4)
My doctor just switched me to Degarelix, 1 month depot, and the values dropped again (Testosterone 0.24, PSA 4.58)

@jeffmarc
thanks for the tip on the RT for people with ATM.

@dinu
Sure glad you saw this. I was thinking of you when I was writing it but failed to include your Mayo name in the discussion.

Interesting that your testosterone was also rising even though you were on ADT. I wonder if this really is a problem with ATM.

Interesting to hear that you’re switching to an antagonist as they recommended during the meeting, and it Actually seems to be working. Hopefully Denis can do this.

I have heard that the PARP doesn’t really work with ATM, but an AI search says it can work. You can try it, but keep track of your blood counts because it’s brutal with your red blood cells and platelets and more. My oncologist has had me hold off on PARP until Everything else stops working because it’s so hard on the body.

Yes, Jeff, thank you. It's unclear why my testosterone levels haven't dropped despite the ADT. Whether this is due to the initially high PSA (531) or the ATM, or both.

In my case, it took a very long time – 18 months – for my PSA to drop to zero. I had numerous metastases, each measuring 3-4 cm.
I know one thing: my testosterone levels have slowed recently and are stable.
I have a hypothesis that something was raising my testosterone levels, but I ruled that out two months ago.
I've recently started having pain in my testicles.
I'll be changing my ADT in January, and I'll have another test in 10 days.

Good luck to everyone, we're not giving up!

Thanks again to Jeff, he's just a great guy!

@jeffmarc
Thanks so much for your reply! And, thank you for the upcoming dates, I'll be sure to put them on my calendar.

My husband is thinking of forgoing ADT since his Testosterone is relative low anyway at 300 and his PSA has never been very high - went from 8.4 then down after the biospy to 7.2. What we've read is that ATM gene mutation PCa does not respond well to ADT. He did finally convince his doc to send his biopsy slides to Artera AI to see if they could give us another data point on whether ADT would be effective treatment for him. Both he and I know that ADT for 18-24 months is recommended for Gleason 9 and radiation, but QOL is extremely important for my husband and he just can't wrap his head around all of the side effects with ADT. He also suffers from depression.

The reason he was approved for Proton Beam Therapy (PBT) was exactly what you mentioned - ATM makes cells more sensitive to radiation including normal cells. So, we're hoping with this that the theoretical benefits of PBT will translate into practical benefits and spare him some of the potential impacts.

@wilkinson1ski

\\ What we've read is that ATM gene mutation PCa does not respond well to ADT

proof, please?

@wilkinson1ski
That testosterone is too high to avoid ADT. The stampede trial showed if it was over 50 it was a problem.

After recently talking with two different people with ATM, there are two ADT drugs that seem to work well. They are antagonists unlike Lupron and other ADT agonists. Orgovyx is The preferred one since it’s a pill. The other one is Fermagon, it has to be injected monthly into the stomach and could be a real pain. I also got this advice from people who are moderators of the mutation online meeting you missed.

Did he get a decipher score? It can tell you the chance of reoccurrence. The thing is with the Gleason nine reoccurrence is pretty common. ADT is recommended because it prevents your system from having the cancer reoccur quickly.

I’ve been on ADT for eight years, You just get used to it. Yes, you lose the desire to have sex, but it is not completely gone for everyone. There are a number of drugs that can be used for depression. People that have mentioned they had this problem have used one of these drugs Wellbutrin, Zoloft, Effexor, Buspirone, Cymbalta, Lexipro, Prozac, Celexa, Paxil And found it relieved the problem. It never caused me to have any depression or actually any mental issues at all, results vary. You should see a doctor about this if the problem comes up.

Here are current NCCN Guidelines in 2025. They now suggest 0 (zero) months of ADT for low intermediate (GG2); 4-6 months for high intermediate (GG3), and 18-36 months for high risk (GG4 and 5). Actually, the footnote suggests ADT + abiraterone for T3b with lymph node involvement.
The meta-analysis suggests:
* 0 months for 1 intermediate factor (PSA 10-20, GG2 or 3, T2b-c)
* 6 months for 2 or more intermediate factors (PSA 10-20, GG2 or 3, T2b-c)
* 12 months for NCCN high risk (PSA >20, GG4 or 5, T3 or 4)
* undefined for NCCN very high risk (2 or more PSA >40, GG4 or 5, T3 or 4)

Looks like I misinterpreted that ADT was not as effective from the beginning, but it seems to say that it is a good first step but ATM will generally become hormone resistant quicker at which time ADT could worsen outcomes.

Here's the paper title:
Hwang, et al (2023) Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes

ChatGPT summary
What this paper studied (in simple terms). This study was based on real-world treatment data, not a lab experiment or a drug trial.
Researchers looked at 1,187 men with metastatic prostate cancer and compared cancers with:
ATM mutations
BRCA2 mutations
Other DNA-repair mutations
No DNA-repair mutations

They asked two main questions:
Do ATM-mutated prostate cancers behave differently from BRCA2-mutated ones?
How do these cancers respond to hormone treatments like ADT and newer androgen-targeted drugs (abiraterone, enzalutamide)?

Key finding in one sentence (ATM + ADT)
Prostate cancers with an ATM mutation tend to respond normally to ADT at first, but once the cancer becomes castration-resistant, outcomes on continued hormone-based therapies are worse than average.

If someone has ATM-mutated prostate cancer:
ADT is still the right first step
But doctors should expect:
Earlier hormone resistance
Reduced benefit from long-term hormone-only strategies
Treatment planning may need:
Earlier consideration of non-hormonal options
Different targeted strategies (not PARP inhibitors alone)

@wilkinson1ski
In this situation, it would definitely be recommended that if somebody with ATM went on ADT they should also go on an ARPI.

The ARPI delays the time it takes to become castrate resistant, Something that could be very important for somebody with ATM. Not sure which ARPI would be best. Maybe starting with Zytiga to keep the testosterone down even further, While it can. Then moving onto one of the ludamides.

I think one of the biggest problems is finding a doctor that really understands these issues. I know UCSF has a pretty Good mutation section, but I’ve only heard about BRCA support. After that meeting, it seems they may cover other mutations like ATM At least they had knowledge about it.

I don’t think @denis76 has become castrate resistant yet since his PSA seems to be quite low. He did fail an agonist ADT drug, Since his testosterone kept rising. Hopefully the antagonist version will not cause the same problem. Another person with ATM said they had found that to work for them.