Interesting paper summarising state of art (2022) for ADT

[Graham49]

The paper below gives a useful summary of the history and state of the art (2022) for ADT. No mention of BAT though. A few snippets from the paper are given below.

Evolution of Androgen Deprivation Therapy (ADT) and Its New Emerging Modalities in Prostate Cancer: An Update for Practicing Urologists, Clinicians and Medical Providers

Choi E , Buie J, Camacho J, Sharma P , de Riese WTW Received 10 November 2021Accepted for publication 16 March 2022 Published 30 March 2022 Volume 2022:14 Pages 87—108 

DOI doi.org/10.2147/RRU.S303215

From Chapter4

“Unfortunately, due to the lack of adequate RCTs we still are waiting for clear answers regarding the oncological benefits of early vs delayed ADT in asymptomatic patients with recurrent or advanced prostate cancer.”

From Chapter 5 on intermittent ADT

“iADT may be considered after at least 9–12 months of ADT or until PSA nadir has been reached (in an ideal clinical scenario with PSA < 0.1 ng/mL). The “off-treatment” period varies depending on PSA monitoring and PSA rising, but also on patient’s and physician’s preference. Again, there are no well-defined recommendations or guidelines at what PSA threshold ADT should be resumed. Some clinicians restart ADT when PSA doubling time (PSADT) is less than 6 months or when serum PSA has reached a level of 6–10 ng/mL. Some clinicians and medical providers set this threshold even far above 10 ng/mL.”

From Chapter 6

“Summarizing the present and available data, it appears that the combined therapy (RT + ADT) is of greatest benefit in patients with high-risk local disease. In addition, some patients with hormone sensitive prostate cancer and low volume metastatic disease may also benefit from combination therapy.”

From Chapter 7

“All four agents (docetaxel, abiraterone, enzalutamide, and apalutamide) have been FDA-approved for the treatment of metastatic, castration-sensitive prostate cancer and are now listed as category 1 recommendations within the NCCN guidelines.81 Treatment choice between agents for metastatic, hormone-sensitive prostate cancer is a challenge, and there is currently no clear consensus on preferential initial selection or sequencing of these agents. There is, however, a moderate degree of uncertainty in the role of chemotherapy in low-volume disease patients.82 Marchioni et al systematically reviewed the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and found that no treatment was superior to docetaxel in terms of overall survival.83 However, abiraterone (HR: 0.89), enzalutamide (HR: 0.90), and apalutamide (HR: 0.90) showed nonstatistically significant lower overall mortality rates when compared to docetaxel.83Abiraterone (HR: 0.71), enzalutamide (HR: 0.61), and apalutamide (HR: 0.74) also showed statistically significant lower disease progression rates when compared to docetaxel.”

From Chapter 9

“Although ADT is an effective treatment for prostate cancer, it comes with many risks and potentially harmful side effects. Therefore, a detailed risk-benefit discussion should be provided to the patient before initiating this form of treatment.”

[cesces]

Thank you so much for the nice summary.

A very very high quality post.

[Gearhead]

Excellent find. Thanks for posting.

A snippet from Chapter 10 might be of interest to others like me who have been taking denosumab for a long time and who have bone density issues (e.g., osteopenia) on the one hand, but concerns about ONJ on the other hand:

Osteonecrosis of the jaw is the most common significant adverse effect of zoledronic acid and denosumab. A retrospective study in 2021 analyzed the incidence of agent-related jaw osteonecrosis in prostate cancer patients: 27.5% developed this feared osteonecrosis of the jaw within 5 years of treatment with a bone-modifying agent.128

27.5% gets my attention!

[PSAed in reply to Gearhead]

Damn this disease, even the "cure" does damage.

[addicted2cycling in reply to PSAed]

Graham49 - THANKS for posting 👍👍

PSAed wrote -- " Damn this disease, even the "cure" does damage. "

Don't you just love the fine print like *.. can cause serious side effects, including increased risk of having a heart attack, stroke, or death from a cardiovascular problem ..*

copied from OP's post ^^^

" ... From Chapter 9

“Although ADT is an effective treatment for prostate cancer, it comes with many risks and potentially harmful side effects. Therefore, a detailed risk-benefit discussion should be provided to the patient before initiating this form of treatment.”

BEFORE SPEAKING with my urologist following my biopsy and additional scans, I decided to have an Orchiectomy instead of using ADT Drugs. My urologist recommended ADT drugs as a first line of treatment but I TOLD HIM that I wanted the Orchiectomy so with some reservations he agreed and less than 24 hours later the boys were GONE.

My uneducated thinking >> better to simply eliminate the offending production line and deal with the lack of *T* and its natural consequences THAN introduce foreign substances that chemically screw around with my body's almost 65 years of doing its own thang. Have non detectable *T* at the moment of writing this reply and in a few hours will be out riding with a group of stronger cyclists and trying to hang on with the non detectable *T*. >>> most likely will fail but the attempt equals Quality of Life

[Benkaymel in reply to addicted2cycling]

Hoping the best for you but be aware that most of the side effects of ADT are due to the lack of T which are the same with orchiectomy.

[addicted2cycling in reply to Benkaymel]

Have spoken to many who have had issues with mental health far surpassing simply LOW T causation

[Doctorsceptic in reply to addicted2cycling]

Yes greatly under reported. Friend of a friend tried to kill himself by cycling into front of a bus. He survived with multiple fractures.

Low T is bad for the brain affects visuospatial awareness and associated with dementia.

[addicted2cycling in reply to Benkaymel]

Benkaymel wrote -- " ... be aware that most of the side effects of ADT are due to the lack of T which are the same with orchiectomy ."

GOT NO *T* right now and IT'S OK WITH ME 👍👍

[Benkaymel in reply to addicted2cycling]

Very glad to hear it and long may it continue. All the best to you.

[maley2711 in reply to addicted2cycling]

There are conclusive studies re the superiority of ochiectomy in terms of side effects?

I'm sure many men would love to know that.

[addicted2cycling in reply to maley2711]

Going out on my ride shortly Without The Boys and enjoying the experience 😉 more better lol

RIDE DONE !!! 52.25 miles feeling tired but GREAT 👍😅👍

[cancerfox in reply to addicted2cycling]

🚴‍♂️🏆👍

[maley2711 in reply to addicted2cycling]

not an answer.

[addicted2cycling in reply to maley2711]

maley2711 wrote 3 hours ago - - " not an answer. "

To what?

[maley2711 in reply to addicted2cycling]

Maybe you did not intend to reply to me...my question was " There are conclusive studies re the superiority of ochiectomy in terms of side effects? I'm sure many men would love to know that. "

[addicted2cycling in reply to maley2711]

OK Just looking at your post I saw ---

maley2711 in reply to addicted2cycling

7 hours ago

not an answer.

--- so thought you had asked me and I wanted to reply. 😀

[maley2711 in reply to addicted2cycling]

you have never answered my question..which I included in 2 different replies to you.....do you see the question re studies and ochiectomy?

[addicted2cycling in reply to maley2711]

"THERE ARE" was taken by myself not as a question even the the question mark at the end so please excuse my miss understanding and ignorance of the sentence structure. *ARE THERE* is how I would have begun the question.

Be WELL.

p.s. - I have never stated nor implied SINCE having the Orchiectomy in April 2015 that it was superior. I have said that men I have spoken with have gone the Orchiectomy route after having very sever side effects from the drugs.

[maley2711 in reply to addicted2cycling]

Sorry for the weird way of asking a question......maybe the way we sometimes ask questions in oral conversation? Yes, I saw a similar remark from someone else today....I asked because most of what I have read found little SE difference......BUT of course that is the "average" of such studies.......just like the much remarked "life expectancy" ...which tell me little about years I have left.

My "?" at the end of sentences is just my way of inviting comments, and done often as sign of humility...is what I'm saying making sense to YOU the reader? or am I nuts??? no need to answer that!!!

[Scout4answers in reply to addicted2cycling]

Admire your spirit A2C

[Cyclingrealtor in reply to addicted2cycling]

Do you think that Kaiser Permanente discussed this with me as part of the evidence based medicine and shared decision making they brag about?

NOPE! Being that I have had NO prior cardiovascular issues but I have family history that is NOTED in my patient file, do you think it would be worth a discussion?

A Kaiser Permanente study published in the "British Journal of Cancer" found that men with localized prostate cancer who received androgen deprivation therapy (ADT) had an 81% higher risk of heart failure compared to those who did not receive ADT. This increased risk was observed in men without pre-existing cardiovascular disease. The study also noted that men with pre-existing cardiovascular conditions who underwent ADT faced a 44% higher risk of arrhythmia and were three times more likely to develop conduction disorders. These findings suggest that while ADT is effective for prostate cancer treatment, it may elevate the risk of cardiovascular issues, particularly heart failure, in men without prior heart conditions.

Kaiser Permanente Research kp-scalresearch.org/androge...

[addicted2cycling in reply to Cyclingrealtor]

I'm thinking the lack of discloser regarding *the bad effects* is far too common AND it is criminal especially when it happens NOW. Stay vertical and keep the cranks rotating. 👍👍

[MateoBeach in reply to Gearhead]

Got my attention too, since other studies have show ONJ rates about 1/10th of that. In the sited study the majority had advanced disease with mCRPC and they measured “ARONJ survival rates”, not incidence. So many died of their cancer or other causes and were grouped with actual ONJ incidence. Therefore this is not a valid estimate of the specific risks of ONJ from these agents.

pubmed.ncbi.nlm.nih.gov/328...

Results: We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1-130 months). Their number of doses of BMA ranged 3-69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%.

[Gearhead in reply to MateoBeach]

Thanks for looking into this with a little more depth. I'm still uncertain about how to interpret the data in the study that you cite, which is Ref. 128 in the ADT review paper that is the subject of this thread. There were "124 and 67 patients treated with zoledronic acid and denosumab, respectively." and "Twenty-eight patients developed ARONJ during the observation period." So, 28/191 = 15%. This isn't the 27.5% mentioned in the ADT review paper. But it's still a big fraction of men taking bone-strengthening drugs along with ADT over many years. And I'm one of those men.

[dentaltwin in reply to Gearhead]

The 27.5% figure comes from the 5-year ARONJ-free survival rate, which was 72.5% (100-72.5=27.5).

I've seen figures all over the map for the incidence of ARONJ. That's likely because a lot of doctors seem to have their own particular regimen for administering these drugs. There are also likely patient factors that may influence incidence (most prominently presence of teeth and dental health). But there's general agreement that the incidence of osteonecrosis increases with the duration that these drugs are given.

[Doctorsceptic in reply to Gearhead]

A lot of posts about osteoporosis and bisphosphonate.

It is really important to be aware of the PATCH trial which shows that estradiol patches are just as effective as standard ADT and avoids the problem of osteoporosis, metabolic syndrome, cognitive decline etc. Estradiol does not help with the muscle loss and the only downside (providing it is dosed correctly) is breast enlargement.

[Papillon2]

👀

[PSAed]

Thanks for posting this valuable information, and the resulting discussion on it is equally informative.

[Doctorsceptic]

Thank you for that post. As a retired doctor I thought chap 9 was absolutely on the money. Too often it is prescribing by rote and protocol without careful risk benefit analysis with consideration of the patient’s wishes and their medical history.

[Graham49 in reply to Doctorsceptic]

Corticosteroids also appear to be risk factor for osteonecrosis of the jaw. The study is for CKD patients but much of it looks relevant. As an ex doctor what do you think?

Risk factors for osteonecrosis of the jaw in patients with chronic kidney disease: a nested case-control study

Ken Iseri, Noriko Hida

Journal of Bone and Mineral Research, Volume 40, Issue 2, February 2025, Pages 262–269, doi.org/10.1093/jbmr/zjae193

Published: 05 December 2024 Article history

[Doctorsceptic in reply to Graham49]

I have not read this study. High dose corticosteroids (CS) alone can certainly cause osteonecrosis of hip and shoulder. I have never encountered it in the jaw in the absence of bisphosphonate use, but of course that does not discount it. The potential confounder in making the connection of course is that many patients on CS will be given a bisphosphonate.

So until I read the article I remain uncertain. I am a retired old fart anyway so what do I know!!!

If I reach a conclusion I will let you know.

[Doctorsceptic in reply to Graham49]

had a look at the abstract. Not sure what to make it and I would really want to read the actual paper. Will try for access.