Could ADT cause castrate resistance

This is EXACTLY what I am thinking and the problems with this PC is that no one knows about any specific questions you ask. My RO wanted to start me on HT when my psa was at .16
I WISH I can have an answer to these questions. Thanks for start a new thread and hope
some of the more experienced guys can share their thoughts.

Provenge, an immunotherapy treatment, can and does provide effective control with low side effects. But for cost reasons, it only gets used after all the older and lower cost drugs and treatments have been exhausted. Early use of Provenge has demonstrated it's much more effective when used that way instead of waiting until patients are standing at deaths door...But insurance companies will seldom approve it until both HT and chemo have failed....

There is another thread running about a new approach to immunotheraoy that holds great promice. But we have to move it past the mouse, chimp stage and get into human trials as quickly as possible..This process should not take 10 years...

Fairwind, have you qualified for Provenge? I would think that would be the next step and it has been shown second line ADT and chemo may be more effective after Provenge than before. Many men are approved for Provenge before using chemo.

Are they comparing apples to apples in these studies? Could it be that Gleason scores are different, pathology reports and findings are different, outcomes of first treatments are different,lifestyles are different, overall health conditions interms of the the immune system being able to fight the disease are different??????? So many factors are involved. Age should not matter at all unless for some of the factors above. My problem is i am fighting for mylife and I can’t get straight answers from doctors. It’s extremely disappointing. Based on this sometimes I think I should have have not done anything and enjoyed my life and may be at most lost a year or two instead of dealing with all of this. My brother had his psa went up to 20 and then went down to 6.5 and he refused to go for even biopsy. He is 72 now and his 20 psa was more than 8 years Ago.

Reachout-

You misunderstood the TOAD trial.You wrote "But without a "no ADT" arm how do we know that ADT didn't cause castrate resistance in both arms, just a deadlier form in the late ADT arm." The delayed ADT arm did not necessarily ever get ADT, and did not get any for at least 2 years of the average 5 years of follow-up. The other arm started ADT at the time of BCR. What they found was that: "One of the most thought-provoking findings was that the development of the castration-resistant phase occurred significantly earlier in the men who started treatment after a delay, a counter-intuitive finding. This may again be linked to treating low volume disease before it grows resistant clones."

The effect of reducing the load of cancer cells in the body seems to more than compensate for any selective pressure exerted by the ADT.

Metastatic PC always eventually becomes castration resistant, whether ADT is used or not. Cancer is genetically unstable and is constantly evolving no matter what we do.

Reachout said...
But with the latest chemos, do we know that ADT is still the best way to go? Versus waiting to see if the disease progresses to the point that ADT and chemo are needed to reduce pain.

We do know that the combination of docetaxel and ADT increases survival significantly over ADT alone. We also know that Zytiga + ADT increases survival significantly over ADT alone. But it may be possible to start with docetaxel monotherapy and move on to Zytiga + ADT. We just don't know, but someday a clinical trial may show that, who knows?

Reachout said...
So, how did we go from this kind of result to a paradigm in which ADT is standard treatment regardless of age?

In that study none of the men received any primary treatment for prostate cancer. Also, a problem with the study was that the men who received ADT, received it because their cancer was more progressed - 34% had poorly differentiated cancer (vs only 14% among those who did not receive ADT). This is called "selection bias." Only a randomized study can avoid it.

In fact, prostate cancer is undertreated in the elderly due to ageism. The decision about whether to treat or not should take into account physiological age, including comorbidities and health status.

You will not find oncological justification for not using ADT in any studies. However, if after you try it, you decide that it impacts your quality of life in a way you don't want to tolerate, it is entirely your choice to forgo such treatment.

Tall Allen said...
What they found was that: "One of the most thought-provoking findings was that the development of the castration-resistant phase occurred significantly earlier in the men who started treatment after a delay, a counter-intuitive finding. This may again be linked to treating low volume disease before it grows resistant clones."
...
You will not find oncological justification for not using ADT in any studies. However, if after you try it, you decide that it impacts your quality of life in a way you don't want to tolerate, it is entirely your choice to forgo such treatment.

Thanks Allen. I had missed that in the trial, significant finding. I don't always like to hear what you have to say, but glad you say it. Good point about there still being an option to go off it if your life turns to hell.

Ak123 said...
Realistically, how many survival years I have left based on my stats?
I know it’s hard to tell but from historical data that are available and predictable disease progression
Thank you

Ak, nobody can really say because there is so much variability. But I have looked up some papers because I am in a similar situation and here is one that is pretty hopeful.

They looked at 61 patients who had failed both surgery and SRT and followed them for a median of 126 months after SRT. They found that the median overall survival was 13.6 years, meaning that half of them lived longer than that. After 126 months only 16.4% had died from prostate cancer.

The negative finding is that the time to BCR was significant to survival time. The critical point was whether you failed within one year, or later than one year after SRT. Those who failed within one year were 10.6 times likelier to die from prostate cancer. But at the low levels of prostate cancer death they found, my guess is that even those guys have a good chance of surviving.

Your numbers are right on the one year threshold, so hang in there. I think they define BCR as two rising readings of 0.2 or higher and you have only one so far. Eat a bunch of broccoli and drink lots of green tea before your next PSA

https://www.renalandurologynews.com/prostate-cancer/good-prostate-cancer-pca-outcomes-possible-despite-salvage-radiation-failure/article/373328/

Advanced PCa is that which is no longer localized to the prostate gland. It is not a measure of risk. One can be advanced and have a very slow growing cancer that is never life threatening. Others can have very aggressive disease that can not be managed.

These are questions for you specialist. They make for good discussion by us patients but they need to part of your professional discussion with your doctor.