Hello everyone, this is my first post. I have been lurking here since late last year and scouring all over the internet for resources for my father. Please read my profile for his background. It has been extremely traumatic and stressful realising his doctors tragic negligence.
I will get to my immediate question to avoid putting everyone through the long story. Basically my dear dad’s cancer has recurred, and he had been referred to the RO far too late. In Oct 2021 he started on Firmagon, PSA has dropped. He will be having whole pelvic irradiation in 2 weeks. I have been reading up on many research and medical papers and can’t seem to get a clear understanding of this aspect - papers have shown that hormones suppresses the tumour by arresting the cancer cell cycle. Radiation works in an active cell cycle, via damage of DNA which leads to cell failure when the cell cycle progresses. With hormone therapy being done in conjunction with radiation, how does this impact the effectiveness of the RT?
Thank you for any input🙏🏻, it is almost 2am here and my anxiety has flared up again when the quiet of the night leaves me with my thoughts.
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My understanding is that given hormone therapy before radiation.will suppress the cancer cells, particularly in the surrounding tissue. Those cells would be newer and more vulnerable. This would centralize the cancer to an area for the radiation to target.
You are already aware of the bad news, that is his sRT has been long delayed. I will try to brink you some good news. I have seen at least 4 papers dealing with the probability of distant spread imaged on PSMA pet as a function of PSA. In a nutshell on an average i.e irrespective of PSA, there are three thirds as follows: 1/3 local recurrence, 1/3 distant or to the bones and finally 1/3 mixed local and distant. It is evident that sRT is effective only on the first 1/3. When the PSA gets higher the first 1/3 shrinks down and the second gains dominance. I see two positive factors in your father's case:
a) He hasn't got a very short doubling time.
b) His pet scan didn't find distant metastases even at the high PSA he had it imaged.
Conclusively, I would say that he has more chances for a positive outcome, some will call it a "cure" but I don't believe there is one such, a long remission being a more realistic term, than his PSA at sRT commencement would prognose. Good luck.
Thank you for all this info and your words, this gives me more hope. I do however think the cancer has spread given he has SVI and had LVI and with the delay the cancer has had more time to grow and spread. A faint nodule showed up locally on PSMA PET at 0.74 but nothing prior. Some papers I have read say this is associated with less aggressive tumour characteristics, but it can also be that the cancer is more diffuse and not visible on scan?
He had RP in 2006. During that the, at the time, cancerous part was dissected. The cause, that nobody knows what it is or its whereabouts, was not. To my view if there was cancer left behind at that time it would had recurred a long time ago. I am GS 4+5 and SVI and had recurrence ~2 years after RP. My view is that the probabilities are in big favour of a new disease caused by the old mechanism that had been put in sleep for years. Nine+ months of PSA doubling time is in many papers considered as the border line between aggressive and not so a disease. This also leads me to believe that he is starting from scratch again.
It goes without saying that I am not here defending his negligent doctors. It would be far better if action had been taken earlier. I am a retired engineer and my general appreciation for the medical profession is that they are still in the middle ages. To give you an example the fact that they give the same dose of a medicine to any patient is the equivalent of making cars with no pedals whatsoever. Only control an ignition switch. Switch on and it moves at the rated fixed horsepower. Switch off and will come to stop sometime-somewhere after this. A couple of centuries after Watt added the centrifugal governor to the steam engine that made the industrial revolution possible there are thoughts/discussions/research in medicine regarding individualized adaptive therapies.
Very interesting, I have never thought of it this way. He did have a long period between RP and BCR, but it does happen whereby pc cells that have escaped come out of dormancy after 10+ years and kicks off. Even in Gleason 6 cases. It is the same cancer. Agree with you on your thoughts on the medical profession.
Agreed, same cancer because the induction mechanism recreating it didn't change.
BUT at what stage? Has it taken off from the stage it was before, has the clock been reset or is it somewhere in between. Lets have a look at how mother nature behaves with materials we live with and know how they perform. There are the elastic, plastic and visco-elastic phases of materials under stress.
Elastic is clock reset, plastic is what has been done can't be reversed and visco-elastic is somewhere in between the two (we say that such a material, like rubber, has "memory"). Choose your father's phase. I would go with elastic, not plastic, visco-elastic at worst. And I am not sugar coating here!
Welcome to the forum. I’m sorry to hear about your father’s cancer, and the urologist ignoring the rise. I can understand your frustration.
I don’t know how the specialists work in Australia, but I have a Medical Oncologist that manages my care, and refers me to other specialists as needed. My Medical Oncologist manages the Androgen Deprivation Therapy (ADT), and refers me to a Radiation Oncologist for specific treatments.
For the vast majority of patients, ADT reduces the cancer to very low levels and keeps it there for years. Testosterone is needed by the cancer for energy, and taking it away causes the cancer to die.
Radiation therapy targets cancer lesions that are found on scans to kill them. It causes a double strand DNA break. When the cancer cell tries to divide (mitosis). The break causes it to die. Since cancer divides rapidly, the death happens quickly.
The two therapies are used together. The radiation killing the large visible lesions, and the ADT killing what can be seen, and what can’t.
Since he hasn’t had ADT previously, the cancer should still be sensitive to it (hormone sensitive). After long term use, the cancer can adapt to the lack of testosterone and start growing again (castration resistant). This usually takes many years. Some members on the forum are still hormone sensitive for decades.
Your oncologist should monitor his PSA on a shorter schedule. PSA can rise at first during treatment, as death of the cancer cells releases it into the bloodstream. After dropping it should remain low. If it rises later on, that is a sign of castration resistance.
Hi there, thank you for your reply! He was referred to the radiation oncologist directly by the urologist. The RO manages everything including hormones. I don’t know if other patients may have another general oncologist to provide more comprehensive care. I will try to find out more about this.
I found this old article about the action of androgen deprivation on cancer cells. It seems the mode of action is via cell arrest but not apoptosis. However other sources say it kills some cells but not all, and certainly shrinks tumour volume. Does this mean there is no chance of eradicating micro metastasis through hormones? Only suppress?
It is my understanding that much of the cancer dies off without testosterone. Some of the cells become dormant, and can later grow without testosterone. The dormant phase can last for a very liong time.
Other members can give you more details, but as long as the cancer is hormone sensitive, the outlook is good.
Thank you for that post Javelin18. In all the years I have had this disease that is the first clear explanation of what is going on. I think the MO assume you know.
You combine ADT with radiation because the combination is more effective. The radiation will still help. Using today's radiation systems they can plan for a higer dose to the recurrence detected on the PSMA scan.
Hormone therapy kills or weakens cancer cells and makes them more vulnerable to radiation. Radiation kills most of the cancer cells eventually; the rest are cleaned up by adjuvant hormone therapy. One of the reasons it is fractionated to assure that they are not in resistant S phase.
ASTRO used to have a great program online teaching radiobiology. Unfortunately it has been taken down so a textbook seems the only avenue currently. It is a deep dive.
I read that radiation triggers dormant cells to enter the cell growth cycle again. So the full course of radiation allows cells to enter the point in the growth cycle (G1,2) where it is most sensitive to radiation.
Well as you already know....you've come to the right place..... It appears to me that you have received some great news here that should alleviate your stress. Please try to learn not to have stress in your life but just joy in having a great Dad. Make sure you and your Dad laugh every day. You are a wonderful offspring that your Dad can be proud of. God Bless.......
Thank you John! It is hard to stay hopeful in these circumstances, chances for SRT success is slim to borderline for dad. Even the preparation for radiation is a struggle (maintaining full bladder etc).I am amazed and inspired by the knowledge and willpower of so many members here. It is invaluable to have all your opinions and support 🙏🏻
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