ASCO GU 2025: New Study Tries to Identify Key Factors That Influence How Quickly Prostate Cancer Becomes Resistant to Hormone Therapy
Androgen deprivation therapy (ADT) is the foundation of treatment for advanced prostate cancer, but many patients eventually develop castration-resistant prostate cancer (CRPC)—a stage where the cancer stops responding to hormone therapy. A new real-world study, analyzing over 41,000 patients treated between 1991 and 2020, has identified several key factors that influence how quickly this resistance develops.
The study compared two common types of ADT:
LHRH agonists (e.g., triptorelin, leuprolide, goserelin) initially cause a temporary testosterone surge before suppressing production over time.
GnRH antagonists (e.g., degarelix, relugolix) directly block testosterone production without an initial surge and may achieve faster suppression.
Patients treated with GnRH antagonists progressed to CRPC faster than those on LHRH agonists. The median time to CRPC was 10.9 months for antagonists vs. 17.3 months for agonists. After adjusting for other factors, antagonist use was associated with a 40% higher risk of faster CRPC onset (HR 1.40, p=0.02).
Other Findings
Patients with metastases beyond the prostate (e.g., in bones or organs) developed CRPC significantly faster than those without metastases.
Patients treated in oncology centers developed CRPC much faster than those managed in urology clinics. This may reflect more aggressive disease in patients treated by oncologists, as urologists typically manage earlier-stage cases.
Patients without diabetes had a 45% higher risk of developing CRPC sooner than those with diabetes
Similarly, patients who were not taking statins had a 43% higher risk of faster CRPC onset than those on statins.
So, in a nutshell:
LHRH agonists may be preferable to GnRH antagonists for delaying CRPC in certain patients.
Patients with metastatic disease require closer monitoring, as they are at higher risk of early CRPC.
The potential protective effects of diabetes and statins warrant further investigation—some diabetes medications and statins may have indirect anti-cancer properties.
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StayingOptimistic
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That’s very worrying reading material… I’m on Degarelix… because I’d read other studies that had said it increased overall survival benefit etc compared to Lupron/Prostap… now I’m scratching my head wondering which studies to trust.
Ah yes I saw that one but without more details I'm not sure you can draw any conclusions. Most likely the result of confounding factors. Personally not worried by this.
I think you are spot on looking at the ’facts’ from this so called study.
One fun fact is they looked at patients between 1991 until 2020. From what I think I seen in litterature Orgovyx was FDA approved 2020 and then avalialble for use in 2021.
I don’t think I’ve seen actual figures of how many are prescribed antagonist (in these study it mainly mean Firmagon but my guess is that standard agonist (Lupron, Eligard and etc.’ Is in the extreme majory compared to Firmagon (and Orgovyx which was not even available until 2021
So lets asume for example agonist patients is perhaps 85 % and then antagonists accounts for 15 % (max). My theoretical point is, with much lower amounts of antagonist patients and having case with some sort of progress gives worse statistics compared with agonist patient with the same sort of progress i really would like to see figures then be told that ’ figures was higher and you have to trust me,,,,’, 🙏😉😂😎
I never trust retrospective studies. It is hypothesis-generating only. Think about why some patients got agonists and some got antagonists. It wasn't random.
I would definitely recommend it. Along with a lot of day to day practical skills of interpreting the world it covers the many biases that can impact scientific research.
Although I've only seen the abstract of this conference paper it looks like poor quality work.
A POSTER?! (A poster is often a physical poster on a large board at a conference. It is like a proof-of-concept for an academic paper, and not subject to the usual approvals. There'll probably be a little discussion and presentation too.)
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From this summary of the poster paper: "Patients with metastases beyond the prostate (e.g., in bones or organs) developed CRPC significantly faster than those without metastases."
That's like saying "people driving to New York city who were already in New York state got to their destination faster than people who started in Chicago!"
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Another interesting note:
"Research funding": Tolmar, Inc.
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2021 news: Tolmar Establishes Tolmar Canada to Sell, Market and Distribute ELIGARD® in Canada
April 2015 I met with my Urologist on the Monday after biopsy and scan results were in. He said I needed to start ADT yesterday and gave me 2 choices, LHRH agonists or GnRH antagonists and I replied that I wanted Orchiectomy.
Good choice and certainly cheaper. If for some reason you wanted T back it’s easy to inj cypionate monthly. So all in all in all a good choice.
Question; since you don’t have to worry about the adt drugs crossing the BBB. Do you still have some T production like from adrenals that can be used for conversion to estrogen for brain health?
KocoPr wrote -- " .... If for some reason you wanted T back it’s easy to inj cypionate monthly .... "
This GL10 Unique Eunuch began biweekly 1ml injections of 200mg/ml Cypionate in January 2016 just 9 months post castration as part of my experimental treatment. *T* levels reached 1,600ng/dL following injection and down to 500ng/dL +/- before next injection when on routine cycle. Had PSA increase in 2018 and the return of lesser GL6 and GL7 in remaining left half of prostate that required stopping injections with a return of *T* <2.5ng/dL after Focal IRE and normal PSA. Have been on/off/on injections since then while watching PSA but currently off Cypionate again because PSA shot to 6ng/mL+ with PSMA PET/CT indicating 3 spots in left half again and biopsy yielding 3 cores of 3+3.
Off of Cypionate now and with left half of prostate remaining has allowed PSA drop to 0.02ng/mL and T<2.5ng/dL both without treatment so still HSPCa and Watchful Waiting with 3 month bloodwork for numbers.
If next month's bloodwork is favorable, might very well go back on Cypionate.
Oh didn’t know you were competing. Ironman really! Amazing! Well consider it if you don’t compete anymore as it does improve energy and strength.
Just an FYI i used 20mg each once per day for 1.5 years of cardarine and osterine while on Orgo/Daro it removed many SE’s and did not cause ALT or AST to rise.
Not competing at this moment BUT have always wanted a third IMFL and the way things are going right now - NO appreciable side effects from the Orchie, getting stronger with more endurance, have a 100 mile ride next Sunday then increase that distance along with walking and swimming, only time will tell.
Hi, I find that so interesting you went for an orchiectomy. When my husband was diagnosed back in May 2024 and we had our first meeting with the oncologist, orchiectomy was never even mentioned. It seems a bit like a taboo subject...We live in the UK where the NHS is struggling and buckling and is underfunded and people in severe pain wait for ages for a hip or knee replacement...one would think, my little cynical voice pipes up, that they would LOVE for guys to have an orchiectomy...a hell of a lot cheaper than Xtandi at around £10k a month...but it was never even mentioned. Even now we're wondering whether that could be an option to put an end to taking Enzalutamide and the Triptorelin and having to deal with its side effects.
My urologist WANTED me to go the ADT way as most men do, but since I don't care for introducing DRUGS into my body the Orchiectomy was logical. Have never regretted it and today approaching the 10 year anniversary of the Orchie, my 75th Birthday with a beaten-up-older-body, I'm doing OK.
p.s. - it's almost never too late to have the boys *Hit the Road* 😁
Hi, thanks for getting back - we'll definitely discuss with out oncologist at our next meeting at the end of March. We both love your sense of humour😂. On a more serious note: I'm also wondering how an orchiectomy affects the spectre of CRPC...
Thank you, wow, that's interesting - I clearly remember us asking our oncologist how much it was and that's the figure he gave...but glad we're 'draining' the NHS less then we thought we did😂
Never had an issue with having the Orchie. My urologist DID for a bit because he tried to dissuade me, but my insistence of wanting it immediately won him over and within 24 hours the Boys were Gone.
I enjoy mentioning this anecdotal tidbit - when the Pathologist checked THE BOYS for testicular cancer he found none BUT NOTED on his report --
*I can Officially confirm that 10 pounds of balls can fit in a 5 pound sack*
This past Sunday I was able to bicycle my upcoming Age plus a little more. Will be 75 in July and managed to bike 79.97 miles and WITHOUT THE BOYS, the ride was sooooo good. 😂
They were gone and I was happy to lighten the load. After the surgery my cycling buddies joked that I should have put them on eBay due to the fact that without really training I was pretty strong and they figured $10,000.00 each ($17,500.00 for both) was a fair price.
I had a lady Onco who insisted I go on Lupron.. I told her I wanted to know what all my options were & she said that was my only option.. i asked her 3 times what other options I had & she said there were no other options but I knew better... I stood up to her & put my finger on her pretty nose & said your FIRED.. She said I couldn't do that and she walked out & slammed the door & I picked up my papers & walked out too and slammed the door and I never went back to her... I had my Orchie soon after and am glad I did... The Docs push Lupron Because they make so much money on it.. Good Luck...
My urologist was fine once I insisted. Everything went smoothly and at post surgery checkup he told me I would be contacted in a week or two by *THE TEAM* to set up a meeting to discuss the TREATMENT PROTOCOL.
Actually in a Ziploc bag hanging from my saddle. This way all the guys can see and realize just how wimpy they are still in possession of their original equipment
I am highly suspect of these findings. Median of 10.9 months to go CRPC with antagonist during a 30 year period of 1990-2020 is looking in rear view mirror.
ADT and treatment options are vastly different today.
Seems like there is a bias built into this "study"
Diabetics may have lower blood sugar levels. statin-users may have lower blood cholesterol levels...I mean generally speaking. These might inversely influence CR development.
I'm on an antagonist, deliberately. So this headline and the associated material was alarming. But the whole thing is garbage. Garbage! Lots of replies highlight why. Especially note Tall Allen's reply.
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Long term AR signaling‐targeted therapy with taxane sometimes associated with visceral metastasis in castration‐resistant prostate cancer
Orchiectomy--any considerations that might be overlooked?
ESMO 2024: Phase 3 evaluation of transdermal estradiol vs LHRH agonists for androgen suppression 
