Here's a review of a recent presentation at ASCO 2023 by Artera.ai regarding the use of Artificial Intelligence analysis of biopsy slides to predict which high-risk men do or don't benefit from short-term ADT vs long-term ADT. Their findings are summarized here:
"Based on these results, it appears that 29% of patients with at least one NCCN high/very high-risk feature would benefit from treatment shortening, given the lack of benefits with long-term ADT for the outcomes of distant metastasis and death with distant metastasis. Conversely, it appears that 43% of NCCN intermediate risk patients may benefit from treatment intensification with long-term ADT to reduce the rates of distant metastasis and death with distant metastasis."
ADT buys time for HR APc patients. How much? Only God knows. A whole lot of us wonder if less than 2 years would be just as good. We are where we are at this point in time, with available treatment arcs etc.
I think Dr. Amar Kishan at UCLA has recently talked about reducing the length of ADT. You might want to look for those results. The work by Artera.AI is exciting because you send them your biopsy slides and they tell if you would benefit from short or long-ADT (or not). It's pretty amazing what they can do now with biopsy slides.
Sadly, they used distant metastases as their endpoint, instead of bRFS. I've never met a patient with intermediate or high risk PCa who didn't prefer curative therapy over non-curative therapies. Would you want to go through salvage therapy for rising PSA? AI doesn't fix conceptual errors.
I think I understand what you are saying. Yes, they only talked about DM in their presentation. But, don't the trends for bRFS, DM, and OS track together, in general? If a certain treatment improves bFRS by a given amount, don't the other outcomes (DM, OS, etc.) improve by a similar amount? I wonder why they chose DM to track... You suggest that bRFS is more important than DM. Why is that? You ask a rhetorical question about what to do when the PSA is rising (post-treatment). What would you do? I don't know what I would do in that situation, because I haven't been treated yet. Seems like one should pick a treatment that reduces both a rising PSA and DM, yes?
There are steps one goes through if therapy fails. The first sign of failure is biochemical (PSA), then clinical (confirmed by imaging and biopsy). If proven, one has salvage therapy. If salvage fails, one may have DM and may eventually die of PCa or some other cause. I have never met a patient who did not want to be cured by his first therapy.
Dan Spratt and I disagree. His belief is that if the patient survives an equal amount of time, it doesn't matter what he has to go through. He believes that OS is the most appropriate endpoint. Because clinical trials do not run long enough to achieve median mortality, distant metastases is a good surrogate endpoint. But ICECAP (a group of researchers who've looked at the data) has found that bRFS is not a good surrogate endpoint. There are too many other causes of death for men who are successfully cured of prostate cancer.
I believe that QOL is as important as length of life. And putting a patient through salvage therapies affects his QOL. The NCCN risk groups are based on bRFS. Dan Spratt would like to change that. I wouldn't.
You can see the difference by comparing the SPPORT trial to RTOG 9601, as discussed here:
Why do you propose 24 months of ADT in other articles? Just curious. I just finish 24 month of Lupron after RT to prostate bed and whole pelvic area. PSA was undetectable over the whole period, PSMA/Pet also clean.
You have to look at the situation. The duration of adjuvant ADT for men getting salvage radiation is different than for men getting adjuvant ADT for primary radiation, or for men with positive pelvic lymph nodes.
This appears so simple I must be missing something. The QOL of successful curative treatment vs lifelong chronic disease, even if OS is nearly identical, is generally worlds apart. Until further notice, chronic Pca is managed with side effect-laden ADT that eventually stops working, while living drug free and dying of something else is clearly superior by far. It seems apples and oranges.
I can only conclude someone who would essentially stand by such a false equivalency has never been on ADT.
I’ve been on ADT for two years now, before that 18 months from 11/2017 and another six months on 2020. So four years in total. With diet, lots of exercising and meditation & lifestyle change I managed side effects not perfectly but pretty well so far. I’m still on a curative path which is amazing. Helps to tolerate the side effects, too.
Thanks for that link !!! Here is one back that doesn't deal with additional markers, but does address ADT duration with radiation..that is the context of your post I'm assuming......
" The treating physician must balance the improvement in prostate cancer-specific mortality in longer treatment regimens with the subsequent worsening of other-cause mortality rates., Furthermore, other challenges to determining the optimal ADT duration include the variable compliance rates with long-term ADT (<80% in some trials) and the variable ADT durations tested in randomized controlled trials. "
" Dr. Zaorsky suggested that in patients with 2+ intermediate risk factors, 6 months of ADT may be sufficient for some. Conversely in the NCCN high risk group patients, the rates of 10-year DM were only 1.1% with 18 months of ADT. As such, do NCCN high-risk patients need 18 months of ADT. The NRG GU009 study is testing 12 months of ADT in this cohort of patients. Finally, there appeared to be a continuous benefit for ADT prolongation in STAMPEDE high risk patients, as has already been established in multiple previous trials. "
" Dr. Zaorsky concluded his presentation with the following take home messages:
The optimal ADT duration in regards to overall survival is ~19 months when accounting for the majority of non-compliance data available with long-term ADT
Optimal duration for cancer-specific endpoints (BCR, PCSM) is likely indefinite
Longer durations of ADT appear to worsen other-cause mortality
This analysis does not account for quality of life or baseline comorbidity status in determining optimal duration
The absolute incremental benefit varies by baseline risk
Optimal risk models should be utilized to better estimate absolute risk and potential benefit of various durations of ADT (STAR-CAP, Clinico-Genomic Risk Groups, ArteraAI, etc.) "
When I look at the graphical results, there is an obvious sharp decrease in incremental benefit as ADT surpasses approx 12 mo., though it appears the graphs represent a blend of results for all risk groups? Still, " the rates of 10-year DM were only 1.1% " for NCCN high risk.
Many believe that either any metastasis or distant metastasis is the most meaningful endpoint. Thus, I'm actually surprised that BCR is used by NCCN when determining who fits into different risk groups.
Re your post and link re the meaning of the 6 month PSA, that might be another valuable "marker" for men concerned about not overtreating themselves with a life-altering therapy?
It will be great to see the results of ongoing ADT duration trials!!!
A doc should consider whether doing something will result in an overall worse result than not doing something. But, except in extreme cases, I doubt they do, especially if their specialty is to "do" what is proposed to be done. Just my thought. More up to the patient to ferret out those details, I suspect.
Of course the key is " will MORE LIKELY THAN NOT result in favorable outcome " from doing the treatment. I believe many/majority of Docs adhere to that...but no wayto absolutely know of course. For both good and bad, Kaiser Doc pay much less tied to doing more procedures just to earn more...downside is Docs avoid suggesting anything that Kaiser does not cover....which some ways makes sense, but in other ways is not good !! "your results will vary" goes with any treatment/drug. all about probabilities of expected outcomes....which is a great advancement from the way medicine was practiced just 60 years ago !
In one way, a sensible "common sense" explanation.....men need T to maintain excellent health.......I doubt any decent Doc denies that, and reading the discussion in such studies, obviously Docs aknow that and are concerned about the damage the treatment can/does bring with it......thus the push by prominent researchers to form a better understanding of which men might not need more ADT to achieve satisfactory "cure" rates. Studies have shown a high percentage of men 70+ enter RT + ADT with compromised bones...ie osteopenic or osteoporotic......and ADT only makes that worse. Some receive drugs to combat that impact, but many don't !
it’s annoying that people only mention ADT durations without specifying neo adjuvant, concurrent , adjuvant usage… here trying to figure this out and only see months mentioned without any detail .. I’ve done research and have an idea but have come to realize most don’t know for sure…
Concurrent and adjuvant win in a number of studies....not sure if really significantly...nowadays Ithink SOC is 1-2 months pre-RT and x months concurrent and adjuvant.
yes saw that ..had 5 months prior to RT here in Japan .. plus dual modality .. brachytherapy and external beam over 2 months or so.. just trying to determine how much adjuvant is beneficial for me in theory unfavorable intermediate but no psa pet scans here and a fairly high PSA …18. so leaning towards more aggressive treatment.. Gleason 4+3 … lesson close to capsule perimeter.
The brachytherapy went well..no bleeding pain or discomfort..slight urgency to urinate. After Linac more noticeable urgency to urinate… like when you are stuck on a bus and have to go..not all the time maybe 5 times a,day.. no bowel issues whatsoever. I finished radiation 5 days ago so supposedly will improve within a few months. The brachytherapy image was very uniformed and well done we were surprised.. a specialist who performs these all the time came to the hospital to work with the primary specialist .. it’s Japan so it’s common. I guess that’s the important point to get someone who is really good at it. I had a lower body epidural so didn’t feel anything.. the worst part would be the catheter some discomfort and blood .. tube was a bit large. That healed quickly. I’m taking lupron and Bicalutamide now on 8th month total. Side effects are weight gain, loss of sex interest, possible boob enlargement .. not very notice for me, and random emotional outbursts. Very manageable in my option and if you workout regularly it will help tremendously. Good luck !
The side effects of radiation are more long term and if my case is typical then from 3rd year onward you will see some side effects in bladder and rectum. If the technicians were first class you will have less side effects.
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