BRCA 1 mutation

[Lawrencee]

ctDNA test revealed a BRCA 1 mutation in 11/23. Estradiol gel stop working in July of 2024. T level around 10. Onc started me on Lynparza / Orogvyx combination. PSA values ranged from 9 - 12 for six months. December 2024 psa droped from 11.4 - 10.1. January of 2025, psa went to 27. Onc thinks Lynparza stopped working, although, it never took my psa any lower than 9. PSMA scan on 10/27/2024 showed several spots, about 9 in locations mainly in muscloskeletal . No organ locations. Onc wants to try Xtandi, says about a 30%. chance it will work. Wanted to consider BAT therapy before Xtandi. BAT not offered at my facility. Thoughts?

[Tall_Allen]

We have actual clinical data that Xtandi+Docetaxel is effective:

prostatecancer.news/2022/10...

[Lawrencee in reply to Tall_Allen]

Thanks for the link to the information. I’ll share with Onc. Do you know where I can check into a BAT trial or any association thereof?

[Tall_Allen in reply to Lawrencee]

Most of the BAT trials are at Johns Hopkins.

[petrig in reply to Tall_Allen]

There is also data that Nubeqa(darolutamide) is more effective than Xtandi(enzalutamide).targetedonc.com/view/darolu...

[Tall_Allen in reply to petrig]

The only way to tell if one drug is more effective than another is with a prospective randomized trial. That has not been done. The link you provided shows a retrospective study, which is flawed by selection bias. Indirect comparisons using RCT data are also flawed for different reasons,

These lead to the opposite conclusions from the flawed study you posted:

This one suggests that Erleada (apalutamide) is more effective than Nubeqa (darolutamide):

pmc.ncbi.nlm.nih.gov/articl...

This one suggests that apalutamide (Erleada) is more effective than enzalutamide (Xtandi):

sciencedirect.com/science/a...

This one suggest that apalutamide (Erleada) is more effective than Zytiga (abiraterone):

sciencedirect.com/science/a...

They are all critically flawed and give the patient no guidance.

[petrig in reply to Tall_Allen]

But if you can choose/ask the drug of course you must follow up different researhes etc .For example research presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.There patients treated with darolutamide were less likely to develop disease metastasis or discontinue treatment 6-18 months after treatment initiation compared with enzalutamide or apalutamide.targetedonc.com/view/darolu...

[Tall_Allen in reply to petrig]

You misunderstand that. They were different patients, so it is incorrect to say say that "patients treated with darolutamide were less likely to develop disease metastasis..." Read the other links I provided and you will get opposite conclusions. The reason is "selection bias," which means the patients given darolutamide were different from the patients given apalutamide. The differences you note were because of patient differences, not therapy differences. The only way to compare drugs is with a randomized comparison to get rid of selection bias.

[petrig in reply to Tall_Allen]

I hear you ..But.. My oncologists first plan was Firmagon+Docetaxel and after chemo Xtandi. I said I want Nubeqa instead of Xtandi for better quality of life. Nubeqa does not cross the blood-brain barrier so maybe I can use it longer and so the result would be better.

I admit that you are right you should trust science,trials,researches and a especially prospective randomized trials but when you have limited time you should be active about your own medication and study widely what information there are .

I still think Nubeqa is the best ARSI you can get today.

Maybe I have " blue and white" 🇫🇮 glasses to look all this .Nubeqa(darolutamide) is result of finnish scientist , study and medical research.

I appreciate your strong voice to defence the cause of truth and science but.. :

“The important thing is not to stop questioning (or learning)”.

Albert Einstein

[Tall_Allen in reply to petrig]

If you are subject to seizures, the fact that it doesn't cross the blood-brain barrier might be important, otherwise not.

"I still think Nubeqa is the best ARSI you can get today." As long as you understand that it is just your feeling, and has no basis in medical science.

Perhaps you can learn how to learn:

prostatecancer.news/2024/12...

[petrig in reply to Tall_Allen]

I am not using AI. I have naturally tried but noticed there are often faults ..I read and study alot. Trials,studies,Lancet,websites..I send email and questions to pharmaceutical factories..I ask oncologists,uroligists,specialists etcThe point is. Be active. Ask,challenge,study. You yourself at last must decide what treatment you want.Of course based on studied truth . Demand the best and latest treatments and drugs.

[Tall_Allen in reply to petrig]

Your doctor trained many years to be an expert, and regularly shares information with fellow experts. If you have an excellent oncologist, that should be your first and best source of information. Frankly, your posting flawed studies and unwarranted conclusions should tell you that you know only enough to be a potential danger to yourself (see Dunning-Kruger in the link below). With some humility, you may come to realize the resource a good oncologist provides.

prostatecancer.news/2024/12...

[petrig in reply to Tall_Allen]

You are in the right oncologists and urologists are the first and best sources but there are choices of treatments specialists offer and you can influence the treatments you get.At least here in europe.My two oncologist wanted to start with Xtandi but because there were different possibilities(enzalutamide,abiratorene ,apalutamide and darolutamide)I wanted the newest, Nubeqa(darolutamide) which was coming to accepted drug for mhspc in Finland January 2024. In January I had 3 docetaxel left so I wanted to start Nubeqa right away in mid of my 6x docetaxel. I am happy I was active finding information and was able to ask that from my oncologists.They accepted. I was not danger to myself,maybe had few extra years for starting triplet therapy with Nubeqa while/together in chemotherapy.So there are choices to talk and ask for your oncologist,urologist or specialist.

They make ,of course,the final decision for your treatments.

But the patient should be there making decisions with specialist after getting the "official" choices .

[Tall_Allen in reply to petrig]

Yes, triplet with either Nubeqa or abiraterone is SOC for newly diagnosed mHSPC.

[petrig in reply to Tall_Allen]

For now Nubeqa should take together with docetaxel(same time).At least in Europe.

[P3Nav]

Xtandi and Lupron have been keeping my PSA undetectable after photon radiation. Have to take Xtandi on a non-empty stomach or you'll feel some discomfort for awhile. No side effects other than what super-low testosterone results in. My Onc said missing a dose or two, like I did when I ran out and needed a refill, isn't critical. Not super travel-friendly as the "pills" are the size of hummingbird eggs, and really bulk up the container they come in.

[Lawrencee in reply to P3Nav]

Thanks. Do you have a BRCA mutation?

[Seasid]

If you have BRCA genetic mutations you shouldn't use estradiol gel as an ADT,

[Lawrencee in reply to Seasid]

Right. My mutation is somatic in occurrence. I learned about that after I was notified about the BRCA mutation via a ctDNA test.

[Shellhale in reply to Seasid]

Hi Can you tell me a little more about using estradiol gel as a substitute for ADT. Husband can't tolerate ADT. Wanting to learn more about this before his MO appointment

[Lawrencee in reply to Shellhale]

I used transdermal estrogen gel. Rubbed it on inside thighs twice a day. One tube lasted about 3 weeks. I purchased from India 25 tubes for around 250 dollars. My email is randypie007 at the g mail

[Shellhale in reply to Lawrencee]

Thank you.Has it helped with less side effects than ADT?

[Seasid in reply to Shellhale]

I don't know much about estradiol gel as an ADT but I am considering bilateral full orchiectomy.

Why do you believe that estradiol is better?

My medical oncologist is doing a clinical trial with ADT plus estrogen injections every 3 months and maybe every 6 months. I am not sure in all of these but I believe the aim is to avoid osteoporosis or who knows what else. In short they are experimenting. As we know you could possibly avoid osteoporosis if you exercise. I am not a doctor but that is what I believe.

Exercise is maybe better what I am concerned.

I am not sure but I believe that they may be use in combination with some other Brest cancer medication.

I am myself not considering using estradiol gel but I wasn't thinking much about it.

[Shellhale in reply to Seasid]

Before ADT was available i know estrogen was used to manage PCa. For men who can't tolerate ADT it can also be an option. As you mentioned it is also better for bone health and can alleviate hot flashes.

[Seasid in reply to Shellhale]

I personally after 6.5 years on degarelix either don't have hot flashes or I am used to it. I just believe that estrogens could have their own problems with prostate cancer plus their own side effects. I will tell you honestly I don't know. I just know that I have anxiety that if I miss the ADT than it will have a negative effects on my cancer.

I believe that my medical oncologist is also hoping like you that estrogens are better but I don't want to risk. Some prostate cancer could have estrogen receptors and estrogens could accelerate the prostate cancer.

I don't really know but I would rather not have estrogen myself. Sorry if I could not contribute better. The good thing is that we are considering possibilities. I am fine without anxiety that with estrogens my prostate cancer could advance at least theoretically plus I am fine without gynaecomastia and breasts cancer. I believe exercise could be better than estrogen for me.

[Shellhale in reply to Seasid]

I believe exercise is always best. I've never seen my husband in better shape then he is now. Movement is medicine. Looks like precision medicine is the future in oncology. Having a mutation seems helpful as it can be more targeted. So much in development right now. I am glad you tolerate ADT very well. This PCa is very different on each patient. Best of health to you.

[Lawrencee in reply to Shellhale]

Thanks for your thoughts. I have a box of gel left over should you want to consider it. I am now mcrpc, not mhspc. Your right, exercise is another piece of this medicinal attach on pca. I am looking into HBOT now, a home unit that is a soft container. Interesting