ADT and resistance proportionality

My Dr said, based on experience with his large patient population over decades, that formation of resistance is somewhat poroportional to ADT dosage. One of his presentations shows that ADT is a risk factor for neuroendocrine form of Pca , which is resistant.

I'm assuming that as the Pca cell is under pressure to survive it mutates in a manner to bypass the threat to it of ADT, including using mutations of the AR receptor to survive this threat

Looking for comments, views and experience with this view.

39 Replies

  • The cancer is always evolving on a much shorter time period than we are. ADT selects out the cancer cells that are sensitive to androgen receptor based treatments. ADT treatments are becoming longer now with second-line treatments such as Xtandi and Zytiga. That gives the cancer more time/opportunities to mutate into a resistant form.

    But for us, the main thing is that we are getting more time to live. We are trying to survive and so is the cancer. It comes down to survival of the fittest. We are fighting the cancer with technology and our understanding of how the cancer cells reproduce, evolve, mutate, etc. The cancer cells just use brute force.

  • Thanks gregg57

    Yes, you are correct; duration is also an important variable as you describe.

    I was thinking of trying to find the best solution with ADT pressure and Time as the variables. What combo of these results in the longest survival time?

    So, as was done in my case, the ADT med is ramped up to max to kill the maximum number of Pca cells first and reach an undetectable PSA level and kept there for a number of months. Then the med is stepped down and if the undetectable PSA level is maintained for a number of months, stepped down again watching if an undetectable PSA level can be maintained, and so on ...

    In this manner, just enough med is used to keep an undetectable level with the least ADT pressure to minimize probability of say, neuroendocrine mutations or ARV7 splice mutation.

  • Now I see what you are asking. I think you are referring to what is called "intermittent ADT" This can be used with localized disease but hasn't shown a difference positive or negative regarding survival. But there is definitely a quality of life improvement when not on ADT so some believe it's worth it.

    For those of us with metastatic disease, it's really not an option due to the associated risk with survival.

    The idea is interesting and still being studied. Here's a recent article:

  • Thanks

    Guess the difference with my hypothesis and the alternating article is , in engineering terms, mine is a ramp up and a sort of asymptotic ramp down, to say 1 pill a day. But it does assume a perfect response. That is, you can get to undetectable and stay undetectable, in the down portion. The article I assume when u go back on ADT u go to full strength ADT

  • Yes Greg, now off ADT for 6 months, side effects down and "quality of life" definitely is improving!


  • I am most likely going to try the intermittent mode regardless of the fact that I am metastatic. I have been on Lupron for over two years and stayed undetectable. Time to try. I need to get my bone density, energy, and muscle mass back not to mention any of my Mojo!! I think it is worth a try. My hope is that the cancer has been knocked down so much that I will have time to rebuild a little before going back. Some studies say it may even slow the resistance transition down because you let the pressure off for a while. Stopping in October if blood PSA, scans etc are good.

  • I'm very interested to know how things go with this so please keep us posted. I'm also curious how extensive your mets are (or were) and also PSA at diagnosis, etc.

  • I had a biopsy that said I was a Gleason 9 and at that time my PSA was somewhere above 12. They did a RRP and 7 weeks later I was in for my follow up and my PSA came back at 9.4. Doctor sent me for a rush PSA and in less than a week I was at 9.61. Scans did not show anything conclusive without biopsy but doctor said same road anyway. Get on Lupron because I am likely micro-metastatic and he ruled out any chance for radiation because I had negative margins and negative lymph nodes at surgical pathology. My PSA went down well with the Lupron going from 9.6 to .41 to .14 and the last reading was .03 and finally after a year it went to <.01 otherwise know as undetectable. I am hoping that if the PSA rises slowly enough I will get a chance at a better scanning to find where it is. It could be one or two spots and only needs a little shot of RT. Don't know till you try, right?

  • Shealy


    With a Gleason of 9

    Good to stay on top of it; I have Gleason

    4+3 ,basically like an 8, now undetectable and believe good chance I am micro metastatic .

    Paradoxically, scans won't show at this Psa, but don't want a rise just to scan.

    I do the guardant 360 blood draw biopsy which looks at Pca fragments and sequences them to find mutations

  • I'm not a doctor, but it sounds like you are good candidate for intermittent ADT because of your low level of mets. My guess is you will probably have a PSA that rises slowly enough that you can get on top of it fairly easily. But you do have a Gleason 9 so you'll definitely want to be keeping an eye on things. Good luck with it and keep us posted.

  • Gregg57

    My scans were all just pre surgery, bone scan, mri all negative

    Post surgery pathology showed no mets, but category called distant mets =unknown

    Psa think pre surgery was 3.8 with normal DRE

    Will stay in touch


  • Good luck!

  • Years ago, when I was new to this "game" someone suggested frequent on/off of ADT, not the normal intermittent approach which might take years to reach the point of going on or off. Rather, we were talking about 3-4 months on, then off for maybe same time (following by psa) and then back on...and so on. But for some reason it never caught on. This discussion suggests that shorter ADT cycles might confuse the cancer cells and prevent successful growth.

    herb s.

  • Worth a try. Some are doing 8 on and 8 off using psa of 4 as a benchmark

  • Think a restatement of this process goals would be: go up to full dose to get max kill of Pca cells , after a few months the goal is to find the minimum dose to stay at undetectable, in a controlled ramp down of med, always making sure you stay undetectable. If can get to , for example 1 pill per week of xtandi from a max normal dose 4 pill per day

    If lucky can stay at the min "maintenance " level, not zero dose approach. Hopefully this may give u more time to resistance by reducing pressure to form resistant adaptation , thereby increasing potential time to resistance

    So it's not really an on/of typical process

  • Definitely my plan. Went for the kill Early on , didnt work.

  • I am on Hormone therapy also and just started a month ago, I feel most of the little pains have subsided. I have wondered why I got pcancer and none of my brothers had any problems, maybe my dad at around 78 started to get up in the middle of the night to urinate but he died of a stroke at 89 with no Pcancer. I am a musician that has traveled all over the country performing. I always tried to eat right, but it is next to impossible going from town to town. I remember my ma telling me to eat my veggies and I would take a couple of bites but not interested in it. when I was a teenager a thought came to me and stuck with me all my life but I ignored it, maybe a premonition I don't know. We are what we eat!! it made sense to me just like a car needs preventative maintain to stay in good condition and we all know that but me I thought if I ate a apple once in a while it was healthy so I was healthy. that was my ignorance to food and nutrition. I wanted to find out why all kinds of berries are anticancer foods. I have been taking B17 because my radiation doc said they are good for you, so I wanted find out why B17 is good for cancer prevention and for a cancer regime and I am using it with my hormone therapy. B17 is actually laetrile and laetrile is in all seeds of berries, raspberries have little seeds in them that we eat along with the berry. nutrionist say eat all kinds of berries because it will prevent diseases. I have been watching a video about the right foods to eat to fight cancer and all diseases too. its keeps coming back to me, I am doing hormone therapy and my cancer is on hold till I get my radiation treatments in 3 weeks. I guess the shot last for 6 months and casodex pill everyday. what I have read that changing the diet can actually feel results in a few days because when we eat something it takes approx. one day for the food we ate last night to go through our bodies so we have energy for the next day. I have decided today to change my diet for my cancer because I have finally realized. I have been feeding my Pcancer along. I am a diabetic also because of my eating habits. but when I was diagnosed with Pcancer . I thought being diabetic made it worse. so I quit eating , Bread, I eat 2 tortillas a day thats it. no more Pasta now that was hard, I love Italian food and Potatoes. I also love mash and frenchfry potatoes. all this 4 months ago. I went to the primary doctor and they did a A1C blood test, I asked the doctor what was the norm for a non diabetic person and he said around 6.3 , he looked at my last A1C test and it was 6.9, he said I was doing good, I told him all the foods I quit eating and he said we can test you now, so maybe he did't believe I could stop eating all those foods. so I was tested and he came back said you really did change your diet, your A1C is only 6 now. he also said I basically reversed my diabetes but stay on the metformin. until we do a another of A1C test in a couple of months. I am now convinced now by changing my eating habits for my cancer along with the ADT, B17, veggies, fruits and radiation treatments I believe I can win this fight , oh yea and being positive and try to stay away from stress. I do believe Stress can create problems too, one of my best friends that I have known since I was 16 and I am 67 now died a few weeks ago and I kept crying at different times during that day and my pelvic area started to ache. I realized being depressed and stressed made it happen. so the next day I had to put his thought out of my mind almost like he was still here, the aches went away and I know now not to be stressed during my Pcancer protocols or any time.

    I didn't mean to go on but I feel this about life and life quality not quantity of the progression of my Pcancer. I have read where PSA goes down to less .3 for a patience, by one of the procedures but then gradually goes back up. I would think that is time to go hard on the nutrition and see if it stays down then you will realize it does work, I know we all know nutrition is good for us but I can tell you from my own experience once it really really comes to your mind to try the nutrition along with all the doctors advise. I believe we can win the fight and I am always in gratitude and compassion to keep my mind away from stress. God Bless us all here at HealthUnlocked to be healed by our own possibilities and information we can share, thank you all for sharing because its good for the positive mind and hopefully anybody that is willing to try the nutrition's that are all out there for us.


  • Robertleeb

    Thanks and much luck to you

    I second the stress element for both Pca and diabetes

  • yes Thank you Podsart, our minds are powerful. I also meditate with the meditation music on youtube. I was having problems sleeping and worrying about all my problems, it seemed to calm the mind going 100 mph.

  • I also do a healing guided meditation from youtube makes me very positive and here is one I started to listen to because he repeats the same things about healing and I seem to fall asleep with head phones with the voice ,and I wake feeling refreshed . I feel if I can get to my subconscience mind where all the stress is built up that I can have another avenue to heal myself

  • Robert,

    I think your decision to adopt a healthier diet is a good idea. However, I don't think you should beat yourself up too much about not having had a healthy diet in the past. I'm not an expert on this (Patrick O'Shea is the expert - have a look at the postings from "pjoshea13") but I do know very healthy guys, one of whom was a vegan for 15 years before his PCa diagnosis. Diet alone may have some effect on slowing the onset and the progression of PCa, but it's not the only factor and, as far as I know, not the major factor in prevention or cure.

    So don't blame your past eating habits for your cancer. S**t happens and it can happen to anyone. The main issue now is how to hold down the cancer for as long as possible.

    Best of luck.


  • Good attitude and outlook.Thank you!

  • Thank you LuLu!

  • Robert,

    Good Luck! We have found that a diet change really made my husband feel better. I recommend the book Radical Remission. It is a really nice and hopeful book about cancer.

    I hope you feel better!

    Many prayers and blessings!

  • Thank you Softwaremom00 ,for the book info, I will look for it.

  • I also read this and recommend spicifically shin's story. Bestvwishes

  • I was diagnosed with aPc 30 months ago. I had diabetes and was obese and I'm convinced that that contributed to my aPc. 4 months ago I started a ketogenic diet. I wanted to improve my biomarkers and immune system to help my body combat the aPc. Since I started Keto I have lost 40lbs without going hungry. My A1C went from 7.9 to 6.6 and I should have the diabetes in remission soon. My cholesterol improved to almost perfect. I have now started probiotic and mushroom supplements. While this may or may not help my cancer it has left me feeling better than 30 years ago. No inflammation and lots of energy. I think nutrition has a lot to do with our well being

  • I am glad your A1C dropped drastically to where mine was before. you are doing the right things to work on you diabetes so it won't create more problems, I have heard people with cancer and diabetes will sometimes the numbers go hi and low, even when eating the right things so it is my belief that my PSA is probably low because of the ADT shot and pill. so I am monitoring more then I ever did just to make sure it doesn't do that. I will keep up the good work and thank you TruckerBob

  • That's fantastic progress!

  • Thats for sure. Just ate junk reastaurant food 31$ and now will have to nearly fast for a day+ to get my system clean. So easy to fall off the wagon. Can see why most are fighting weight problems. Rocco

  • You, like I , love food..They say food is gods love made edible.It is up to us not to go over board .I admit I just ate a steak sandwich ,fries,and a ice cream wife is way from me for a couple days for the first time in five years that we've been separate for more than one day. Anyway, anything is o k once in awhile.That comfort food is easy to fall back into .Then I say to myself back to the diet. But for 1/2 an hour I was in culinary bliss.

  • When I think of ADT injections I think of time periods, not dosages. I was given a six month eligard injection. I am off it now. I wanted to see if my surgery was effective and couldn't do that if ADT was still suppressing PSA. So far, so good.

  • Have any of you heard of or your doc mentioning the Vantas Insert for ADT?

  • For those considering intermittent ADT, I suggest also discussing "Bipolar Androgen Therapy" ("BAT") with your oncologist. As I understand it, the theory behind BAT is that, first you "starve" (it's not really starving but cutting off signaling molecules) the tumors of testosterone, causing many cells to die off and cells that have beefed up androgen sensitivity (e.g., more androgen receptors on their cell surfaces), to dominate the tumor cell population. Then you blast them with very high testosterone levels, overwhelming the now overly sensitive tumor cell population and killing off those cells. Then you keep going back and forth.

    It sounds a little crazy but there's apparently increasing empirical evidence that it works.


  • I heard about the intermittent ADT, sounds interesting thank you for that info, I want to talk to my doctor.

  • Robertleeb

    Will be interesting to see what he says; just remember my dr process in this case is really different than intermittent ADT

    Much luck

  • Sounds very hopeful.Thank you Alan!

  • One of the approaches they are now using is to hit the cancer with a number of ADT drugs at the start. For example, the Stampede trial showed dramatic improvements in life and time with non detectable PSA by using a combination of Lupron and Zytiga (with prednisone) as a first line treatment vs starting first with Lupron then going with Zytiga. The thought is that while both are ADT treatments they operate by different mechanisms. It is like hitting cancer with both fists instead of just one.

    A different trial is showing great potential by using a mixture of Lupron and chemo at the start. The same basic theory as above.

  • I was in a similar situation... I went on a Plant-Based Diet eliminating all dairy and meat and I took the following drugs and still take them everyday...

    4-Methylumbelliferone (4-MU or Cantabiline) 400 mg q.d. (3x day). Blocks PCa metastasis by abrogating HA signaling and hyaluronic acid synthesis. In recently released Paper Clip documents from WWII 4-MU was tested on concentration camp prisoners and reversed metastatic prostate cancer to the bone in 100% of the concentration camp. These amazing studies only became public recently with the release of the Paper Clip documents. Operation Paper Clip was the United States name for our bringing thousands of Nazi scientists to America which remained highly classified until just recently. 4-MU does NOT lower PSA but it does block metastases to the bone and seems to also be able to reverse bone metastases as well. This drug is available without a prescription throughout Europe and cost about $4 for a month's supple.

    Isosilybin B 48 mg b.i.d. (2x day) Blocks androgen receptors through a different mechanism than drugs like Casodex (Bicalutamide) and unlike Casodex does NOT stop working after extended use. Anti-tumor action in bladder and prostate cancer cells. You can buy Life's Extension's European Milk Thistle which contains this drug.

    As I said, I was in your same situation and today I have signs of bone mets and my PSA is literally ZERO.

    Good Luck!

You may also like...