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Re radiate

User
Posted 01 Jul 2024 at 14:21

Can a prostate have a second dose of radiation. 

Thanks 

User
Posted 02 Oct 2024 at 11:49

Well, your prostate isn't mush after radiotherapy. Actually, quite the opposite - it's firm and inelastic due to fibrosis.

Radiotherapy is not like sticking your prostate in the microwave for 10 mins, which is what a lot of people imagine. It's actually very selective for killing the cancer cells or stopping them from being malignant (i.e. can't grow and spread), while leaving the non-cancerous cells untouched.

Cancerous cells became cancerous by getting corruptions in the genes in their DNA. Genes are like little computer programs. If they go corrupt, they won't work anymore or will do something different than intended. Genes actually go corrupt quite frequently, probably daily in each cell's DNA. There are many genes who's job it is to repair different types of corruption in the DNA - you will know of some of them such as BRCA1, BRAC2. However, if one of these genes gets corrupted, then some types of DNA repair are no longer possible in that cell. That's not a problem until some more corruptions happen. If they happen in genes controlling a couple of specific cell functions, then you have cancer. These are the genes responsible for deciding when the cell should divide and multiply, which is a normal function to produce new cells to replace dead ones. However, if that starts running out of control, the cell will be producing lots of replicas of itself, with the same broken genes, and then you have a cancer growing. There's a similar function for cell death (apoptosis). Cells in your body don't normally live to the point of dying of old age, because you'd have lots of old dysfunctional cells - they commit suicide when they're past their prime, so the bulk of cells in your body are in their prime. This is controlled by genes too, and if those genes stop working, then the excess bulk of cancer cells will grow even faster.

So cancer cells typically have 3 mutations - unable to repair gene mutations, dividing and multiplying too fast, and not killing themselves so they do live much longer until they die of old age. Radiotherapy exploits the first of these - unable to repair gene mutations. It generates large amounts of free radicals in the cell, and these generate loads of gene corruptions. Over the next 24h, the gene repair programs run and repair these corruptions. Except, in the cancer genes, not all types of corruption are repairable, in which case the corruptions remain. Next day, another dose of radiotherapy does the same, and again, the healthy cells repair their corrupted genes, but the cancer cells can't and accumulate more gene corruption. As this is repeated, the cancer cell genes are accumulating more and more corruptions, while the healthy cells keep repairing themselves. At the end of the radiotherapy, the intention is that the cancer cells are sufficiently corrupted that the genes which are involved in cell division/multiplication can't work anymore, which means the cell is no longer malignant, and the cancer can't grow or spread anymore.

This is an idealised description. It's not as clean as this though. There is collateral damage to healthy cells too. In order to be pretty sure all the cancer cells are non-malignant by the end, the radiotherapy dose is set so the collateral damage is low enough that enough healthy cells survive to enable the organ to repair itself. That percentage of collateral damage depends on the organ and I don't know what it is for the prostate, but it's probably something along the lines that the prostate can recover providing you don't kill more than, say, 10% of the healthy cells in the process. Radiotherapy dosing is based on getting that balance right - enough to knock out all the cancer, but not enough to kill the prostate or leave large areas necrotic. If you did have large areas of necrotic tissue left, that would result in sepsis and your death as the body would not be able to fight infection there. The prostate has to work well enough afterwards to be able to fight off infection and maintain its tissues.

The repeated radiotherapy and healing cycles generate a lot of scarring and resulting fibrosis as that heals. This makes the organ hard and inelastic which is the main reason it no longer works for producing semen (it's normally soft and muscular), and very likely damage to the ducts too. However, not so much damage that the blood supply is compromised, so the body can still maintain it.

There has been a concept of max lifetime dose to any tissues for almost 100 years since the work of Claudius Regaud in the 1920s, which calculated the dosing and fractionation required to kill cancer cells (although bizarrely he actually did this by working out the dose required to sterilise ram's testicles without permanently damaging their scrotal skin).

It's only relatively recently that we started experimenting with changing his findings, which brought in the shorter treatment sessions using hypofractionation (20 fractions) and ultrafractionation (5 fractions).

It's even more recently that we've considered that after many years of healing, another dose to the same area might be possible, sufficient to kill cancer, but not too many healthy cells. This isn't standard practice in the UK (or anywhere yet as far as I know), but has been done experimentally. The challenge will be to find if there is a balance between doing too much damage and killing the cancer, and that window is probably much smaller and possibly virging on the non-existent for a second treatment to the same area.

Edited by member 02 Oct 2024 at 11:56  | Reason: Not specified

User
Posted 01 Oct 2024 at 22:30

Decho, If you are correct that it is the prostrap rather than the lack of testosterone causing side effects (which in your case the evidence points to), then should you find yourself needing ADT for life, I think a different HT drug such as Zoladex would be the starting point.

Orchidectomy is irreversible, it is not impossible that a genetic-immuno cure for cancer could be achieved in our lifetime. I would be reluctant to have orchidectomy unless I was sure the drugs were the cause of severe side effects. Anyway let's hope neither us will have to go down that route 

Dave

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User
Posted 01 Jul 2024 at 15:54

In the UK, no, because it's had its max lifetime dose.

An exception is if an area was missed with seed Brachytherapy, in which case they can insert extra seed(s).

However, there is increasing thought that if the radiotherapy was years ago, then some further dosing might be possible, and this is done in some countries. One eminent UK oncologist has said we need to get more brave here.

Focal therapies might be an option for recurrence in the prostate, as might be salvage prostatectomy.

Edited by member 01 Jul 2024 at 15:56  | Reason: Not specified

User
Posted 01 Jul 2024 at 23:26

Research is starting in this area.

https://bmjopen.bmj.com/content/12/11/e068580

I think it will be a long time before we know the answer. 

Dave

User
Posted 02 Jul 2024 at 06:38

Thanks for the replies.  

Would the most common treatment for BCR after radiation be ADT 

Thanks

User
Posted 02 Jul 2024 at 08:37

Originally Posted by: Online Community Member

Thanks for the replies.  

Would the most common treatment for BCR after radiation be ADT 

Thanks

That is correct. Once in a blue moon you hear of another treatment, I think Barry had HIFU after RT, but 99% of the time it will be a case of wait a while until PSA gets to somewhere in the region of 10 or 20 and then start ADT for life. 

Dave

User
Posted 02 Jul 2024 at 12:28

I was told they will only do HIFU as salvage treatment for failed RT if the cancer is thought to be confined to the Prostate. I have had HIFU twice, the last time being in December 2021. My recent PSA has dropped from 0.06 to 0.04 and I was told I am in remission. Prior to the HIFU I did inquire whether I could have further radiation and was told that this was possible providing the path of the beams could largely avoid the paths of the original RT beams so this would need to be establised. I did not pursue this as I had my original RT abroad and I doubted whether the original beam paths could be found.

With the greater precision.now being achieved with radiation, more possibilities are now becoming possible.

Edited by member 02 Jul 2024 at 14:59  | Reason: Not specified

Barry
User
Posted 01 Oct 2024 at 15:21

I feel a bit cheeky butting-in to disagree as a newb here, but I don't think this advice is correct at all, and could be very worrying and harmful.

NHS England policy is that some presentations of recurrence, according to strict criteria, can be treated with SABR therapy so long as planning constraints (lifetime tissue dose) are respected.

metachronous-extracranial-oligometastatic-cancer.pdf

The PSA trigger level is something like 2, NOT '10 or 20', also doubling-time is considered.

Search on this forum for more info.

HTH

Originally Posted by: Online Community Member

That is correct. Once in a blue moon you hear of another treatment, I think Barry had HIFU after RT, but 99% of the time it will be a case of wait a while until PSA gets to somewhere in the region of 10 or 20 and then start ADT for life. 

Edited by member 01 Oct 2024 at 15:22  | Reason: typo

User
Posted 01 Oct 2024 at 19:16

Hi Andy, all opinions are welcome. Getting the best information out there is what we are aiming at.

As the thread title is "re-radiate" and the first post is about re-radiating the prostate. I was thinking more in terms of treatment of the prostate rather than distant mets. Yes SABR for distant mets is possible, so if that is the cause of BCR and other things favour it then that is a good option. However if the recurrence is in the prostate it almost certainly isn't an option due to life time dose of radiation.

PSA 2 (+nadir) is when they will classify BCR as started, but that does not mean they will start treatment at that point. You will be back under observation of an oncologist and she will make a decision about the progression of cancer (PSA and doubling time) Vs Quality of Life, and other medical considerations. Assuming no other treatment of the prostate is possible (which is about 99% or the time, but I stand to be corrected), the oncologist will probably delay ADT as long as possible to allow the patient the best quality of life for as long as possible, in most cases this will be when the PSA has got quite high, one poster on here still declined ADT until his PSA was near 1000. Most oncologist seem to be reluctant to let it get that high and somewhere in the region of 10 to 20 is when it will be recommended to start ADT. If a man is in his 80s with a life expectancy of ten years, the possibility of delaying ADT even when BCR is obvious may give him an extra year or two of a sex life in his early 80s at the risk of losing all his life in his later 80s.

Thanks for prompting me to clarify my post hopefully it will benefit everyone. 

Dave

User
Posted 01 Oct 2024 at 22:05

Originally Posted by: Online Community Member

Thanks for the replies.  

Would the most common treatment for BCR after radiation be ADT 

Thanks

Yes, but you could consider an orchidectomy. I know it maybe sounds drastic but I would certainly consider it if I was told I would be on ADT for life.

User
Posted 01 Oct 2024 at 22:30

Decho, If you are correct that it is the prostrap rather than the lack of testosterone causing side effects (which in your case the evidence points to), then should you find yourself needing ADT for life, I think a different HT drug such as Zoladex would be the starting point.

Orchidectomy is irreversible, it is not impossible that a genetic-immuno cure for cancer could be achieved in our lifetime. I would be reluctant to have orchidectomy unless I was sure the drugs were the cause of severe side effects. Anyway let's hope neither us will have to go down that route 

Dave

User
Posted 02 Oct 2024 at 06:16

Recurrence after radiotherapy has three distinct treatment paths:

1) Centres which don't have PSMA PET scanning and SABR capabilities will often simply put patients on life-long hormone therapy without being able to tell where the recurrence is. You really need to get referred somewhere with better diagnostic and treatment options if you hit this stage, as this hasn't been the NHS standard of care for many years now, but there is a reluctance for centres to refer someone on when diagnostics or treatments beyond that centre's capabilities are required, unless the patient knows to ask or organise it themselves.

2) Recurrence outside the previously treated area. In this case, you may be eligible for SABR treatment for up to 3 mets. This doesn't have a high cure rate even though it is given with curative intent, but even when it doesn't cure, it does significantly push out the need for life-long hormone therapy, and is considered worth it on those grounds. Sometimes, this can be done again later too (particularly privately, NHS less likely to but not unheard of).

3) Recurrence in the previously treated area. This is relatively rare with radiotherapy, but it does happen. As I said before, some countries will now consider more radiation if the original radiation was a long time ago, but the UK doesn't as yet. In the case of the prostate, salvage prostatectomy may be available, but ideally this needs to be done by a specialist in salvage prostatectomy, and on the NHS, that's mainly at Guys and St.Thomas's. Focal therapies may be an option too, but as far as I know, they're still not available north of London on the NHS.

User
Posted 02 Oct 2024 at 07:25

Hi Dave,

Yes, I know it’s a big deal to go down the way of orchidectomy, and I would explore all other options first before going  down this route, maybe even go back on Prostap to see if it affects me differently….I’ve learned a lot from this experience. My CNS told me Prostap was actually the kindest as far as side effects go!

The reason I’m carefully monitoring my progress since finishing HT is to determine whether it’s the Prostap or lack of testosterone that caused my joint problems. I can honestly say that my joint aches have almost gone and energy levels are high, even thought my testosterone is still undetectable….I think my next PSA/Testosterone Test at the end of the year is going to be interesting. I still get hot flushes but they are not nearly as bad as before, if I went back on ADT I would definitely try one of the drugs available to help with these.

User
Posted 02 Oct 2024 at 07:30

Very informative post as always Andy, I’ve always wondered though why they can’t retreat an area that’s already been treated with RT. If your prostate is mush anyway what’s the problem in treating it again?

User
Posted 02 Oct 2024 at 11:49

Well, your prostate isn't mush after radiotherapy. Actually, quite the opposite - it's firm and inelastic due to fibrosis.

Radiotherapy is not like sticking your prostate in the microwave for 10 mins, which is what a lot of people imagine. It's actually very selective for killing the cancer cells or stopping them from being malignant (i.e. can't grow and spread), while leaving the non-cancerous cells untouched.

Cancerous cells became cancerous by getting corruptions in the genes in their DNA. Genes are like little computer programs. If they go corrupt, they won't work anymore or will do something different than intended. Genes actually go corrupt quite frequently, probably daily in each cell's DNA. There are many genes who's job it is to repair different types of corruption in the DNA - you will know of some of them such as BRCA1, BRAC2. However, if one of these genes gets corrupted, then some types of DNA repair are no longer possible in that cell. That's not a problem until some more corruptions happen. If they happen in genes controlling a couple of specific cell functions, then you have cancer. These are the genes responsible for deciding when the cell should divide and multiply, which is a normal function to produce new cells to replace dead ones. However, if that starts running out of control, the cell will be producing lots of replicas of itself, with the same broken genes, and then you have a cancer growing. There's a similar function for cell death (apoptosis). Cells in your body don't normally live to the point of dying of old age, because you'd have lots of old dysfunctional cells - they commit suicide when they're past their prime, so the bulk of cells in your body are in their prime. This is controlled by genes too, and if those genes stop working, then the excess bulk of cancer cells will grow even faster.

So cancer cells typically have 3 mutations - unable to repair gene mutations, dividing and multiplying too fast, and not killing themselves so they do live much longer until they die of old age. Radiotherapy exploits the first of these - unable to repair gene mutations. It generates large amounts of free radicals in the cell, and these generate loads of gene corruptions. Over the next 24h, the gene repair programs run and repair these corruptions. Except, in the cancer genes, not all types of corruption are repairable, in which case the corruptions remain. Next day, another dose of radiotherapy does the same, and again, the healthy cells repair their corrupted genes, but the cancer cells can't and accumulate more gene corruption. As this is repeated, the cancer cell genes are accumulating more and more corruptions, while the healthy cells keep repairing themselves. At the end of the radiotherapy, the intention is that the cancer cells are sufficiently corrupted that the genes which are involved in cell division/multiplication can't work anymore, which means the cell is no longer malignant, and the cancer can't grow or spread anymore.

This is an idealised description. It's not as clean as this though. There is collateral damage to healthy cells too. In order to be pretty sure all the cancer cells are non-malignant by the end, the radiotherapy dose is set so the collateral damage is low enough that enough healthy cells survive to enable the organ to repair itself. That percentage of collateral damage depends on the organ and I don't know what it is for the prostate, but it's probably something along the lines that the prostate can recover providing you don't kill more than, say, 10% of the healthy cells in the process. Radiotherapy dosing is based on getting that balance right - enough to knock out all the cancer, but not enough to kill the prostate or leave large areas necrotic. If you did have large areas of necrotic tissue left, that would result in sepsis and your death as the body would not be able to fight infection there. The prostate has to work well enough afterwards to be able to fight off infection and maintain its tissues.

The repeated radiotherapy and healing cycles generate a lot of scarring and resulting fibrosis as that heals. This makes the organ hard and inelastic which is the main reason it no longer works for producing semen (it's normally soft and muscular), and very likely damage to the ducts too. However, not so much damage that the blood supply is compromised, so the body can still maintain it.

There has been a concept of max lifetime dose to any tissues for almost 100 years since the work of Claudius Regaud in the 1920s, which calculated the dosing and fractionation required to kill cancer cells (although bizarrely he actually did this by working out the dose required to sterilise ram's testicles without permanently damaging their scrotal skin).

It's only relatively recently that we started experimenting with changing his findings, which brought in the shorter treatment sessions using hypofractionation (20 fractions) and ultrafractionation (5 fractions).

It's even more recently that we've considered that after many years of healing, another dose to the same area might be possible, sufficient to kill cancer, but not too many healthy cells. This isn't standard practice in the UK (or anywhere yet as far as I know), but has been done experimentally. The challenge will be to find if there is a balance between doing too much damage and killing the cancer, and that window is probably much smaller and possibly virging on the non-existent for a second treatment to the same area.

Edited by member 02 Oct 2024 at 11:56  | Reason: Not specified

 
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