IRE-CT as a probable option

[CrocodileShoes]

I've just returned from visiting the Vitus Clinic in Offenbach tp discuss a possible way forward. My circumstances: Experienced BCR late 2017. MO prescribed Casodex 150mg as monotherapy, which has kept PSA <3. Now has risen to 3.7 so time to act. PSMA scan and yesterday's MRI showed it's still localised but with seminal vesicle involvement. No discernible mets. Original Gleason 3+4.

Prof. Stehling was very clear, very honest. He said that he'd favour 7 probes to give full-gland ablation, and didn't feel the SVI was an issue. He's treated over 1000 patients with nano-knife and said many had SVI. The unevaluated addition is electro chemo-therapy (with Bleomycin) administered at the same time as the IRE. He's been doing this for 2 years (although it's been done on skin cancers for much longer) The theory is that the IRE ensures that the mitochondria are much more receptive to Bleomycin. He also talked about the collaboration they have with a clinic in Cologne, where they're looking at immuno-follow up because, as he put it, 'we all have cancer cells in our bloodstream - so it's foolish to talk about curative treatments.

Risks: small risk of fistula in rectum; smaller risk of pulmonary fibrosis (due to Bleomycin, but as it's a 'one and done' treatment, that shouldn't be great). Overall side effects seem minimal, and it only involves an overnight stay, with patients travelling home next day.

For me, it's either this approach, or start on Lupron. Prof Stehling's view was that if IRE-CT delays the point at which ADT starts, it delays the point at which you become resistant. I'm inclined to go with it.

Just wondering if anyone has any views on IRE-CT as a 'belt and braces' strategy?

[GP24]

Treating a recurrence after RT using local therapies is always a problem, no matter what treatment you select. I have a friend who got IRE for a recurrence after prostate radiation. His urethra was severely damaged by IRE so he had to have several TURP surgeries after that. He had these when self-catheterization did not work any more. Now he has a permanent suprapubic catheter and is very unhappy with the IRE treatment he got.

I guess this happened because the urethra was already damaged to some extent by the radiation treatment he had got before the IRE. And IRE did further damage to it.

Here is another report of a failed IRE treatment after radiation:

translate.google.com/transl...

He writes: "Pre-irradiated IRE patients should first receive self-catheterization training."

[CrocodileShoes in reply to GP24]

Hi,

That's quite a sobering thought. I notice that you had IRE yourself. DId you have it done at Vitus, and what was your experience?

[GP24 in reply to CrocodileShoes]

I had it at Vitus as a primary treatment that is different to a pretreated prostate. I had an urethral stricture and needed a TURP. That did help. Vitus did not treat the seminal vesicles so I had Cyberknife to treat the recurrence in the seminal vesicle 18 months after IRE.

[CrocodileShoes in reply to GP24]

That's really helpful to know. DId the TURP resolve the issue? And have you had any further recurrence? I guess I need to talk to some patients who've had IRE following radiation!

[GP24 in reply to CrocodileShoes]

It did not completely resolve the issue since it takes me about three times as long to pee as it does for a healthy man. But I read you can only have to two TURPs and then you should start with reconstructing surgery. Means they take your oral mucosal membrane to reconstruct the urethra with open surgery. Therefore I will not touch the urethra again if I do not need to.

I had lymph node mets detected with a PSMA PET/CT before having the IRE treatment. So I am constantly zapping any visible mets as long as it is possible to do so. Reduces the PSA value and thus delays the ADT.

[Tall_Allen]

If you know the cancer is in the seminal vesicles, and IRE cannot be used on the seminal vesicles, then what is the point of pursuing this salvage therapy? I think your odds are better with either focal salvage HDR brachy to the seminal vesicles, or focal or whole gland salvage SBRT. There are several doctors who have tried this in Europe (see links):

pcnrv.blogspot.com/2016/08/...

However, I think that considering the amount of time that has passed since BCR, and the fact that the cancer has progressed to castration resistance, it is likely the cancer is systemic, even though mets are not large enough to be detectable with current technology. Given this, and the unknown and probably very limited effectiveness of local treatment in the CRPC setting, I think you should think twice about any therapy that might create a fistula, even if the probability is low. Darolutamide (Nubeqa) has recently been approved for this situation, and seems to have a very favorable side effect profile.

[CrocodileShoes in reply to Tall_Allen]

I don't think I said that IRE could not be used for SVI.. certainly Prof Stehling seems to think it's not an issue, and he's treated many men with SVI. Of course there could well be micro mets already out there, but that's where the electro chemotherapy appeals. Stehling seems fairly sure that the twin process sets off an immune response.

I need to understand more about the castration resistance process. Are you saying that resistance to Bicalutamide means resistance to any ADT strategy?

I guess my conversation with Stehling had echoes of the Leibowitz position: that the later one can delay ADT is a day later that resistance sets in.

In the meantime, my MO suggests that I start Lupron with Bicalutamide 50gm . But I will certainly look at Darolutamide.

Thanks for taking the time to respond.

[GP24 in reply to CrocodileShoes]

Please be aware that your discussion with Prof. Stehling was a sale talk for him. He has not treated many man with SVI. The micromets can be anywhere in the body, not just where the IRE is used. In this area the IRE will destroy the cancer and there is no need for electro chemotherapy. Is there any proof apart from what Prof. Stehling said, that there will be an immune response? If he wants to use nine needles I think he will simply treat the entire prostate again - and thus cause urethral stricture. You do not need nine needles for the seminal vesicles only. He used five needles for my entire prostate.

[CrocodileShoes in reply to GP24]

Sorry, if I misled you. He suggested 7, not 9, needles. And that's to treat the whole gland and SVI. The theory behind adding ElectroChemo is to address any micro escapes. But, I want to stress, he was at pains to say that he wasn't selling a 'cure'.

I sense that you have not had a good experience with Vitus? If you'd prefer a DM/offline discussion, I'd be very appreciative.

Best wishes,

[GP24 in reply to CrocodileShoes]

I do not understand why the whole gland needs to be treated again if there is just a recurrence in the seminal vesicles. Only these need to be treated to avoid side effects.

IRE is rarely used for recurrence after radiation. I mentioned two patients who had big problems after that treatment. So IRE to treat a recurrence is asking for trouble.

The IRE worked for me but I think I was lucky to get away with just a TURP following the treatment.

[CrocodileShoes in reply to GP24]

Sorry, I haven't been clear (again) My PSMA taken in February showed that there was bilateral recurrence, with seminal vesicle involvement. So, it wouls need the gland and the SV to be treated. The Plos One research paper they had published suggested a relatively large number of men treated after recurrence, and their results were impressive. I've seen other studies showing IRE used successfully to treat recurrence. So, could you point me to any research that suggests that IRE to treat a recurrence is 'asking for trouble'?

I'm not committed to this course of action - just need evidence one way or the other!

[GP24 in reply to CrocodileShoes]

With PlosOne do you mean this article:

journals.plos.org/plosone/a...

The authors all work for Vitus. Except Rubinsky who developed the IRE treatment.

[GP24 in reply to CrocodileShoes]

You wrote in the other thread: "I had the triple treatment: Casodex, followed by HDR Brachy, followed by EBRT (low dose) " I am really surprised that HDR brachy combined with EBRT results in bilateral recurrence, with seminal vesicle involvement. Just as if nothing worked. I would get a prostate biopsy to check the results of the PSMA PET/CT or another PSMA PET/CT at a different clinic.

[CrocodileShoes in reply to GP24]

At the time of the initial treatment (2009) my MO was following a protocol which had been reported in Canada. After 5 years, it showed an 85% disease-free survival - I was obviously just one of the unlucky 15%. I had 7 years of PSA below 1.0, but it only takes one cell.....

[GP24 in reply to CrocodileShoes]

I would assume the 15% mainly had a recurrence outside the treated area, this does not mean that new lesions appear in the radiated area. It is difficult for me to believe there is a bilateral recurrence with seminal vesicle involvement in both vesicles. Considering that you have a Gleason 7, this is very unusual. Therefore, before any salvage treatment I would try to verify the results of the PSMA PET/CT. Here is an article about "Pitfalls in Gallium-68 PSMA PET/CT Interpretation"

ncbi.nlm.nih.gov/pmc/articl...

[Tall_Allen in reply to CrocodileShoes]

Can IRE be used on the seminal vesicles? I thought it is used in normal tissue where the electrodes can be placed at a fixed distance? Does he get complete ablation in that sort of tissue?

Probably there is an abscopal effect with any kind of radiation or ablation, so that should not enter into the decision.

Resistance to bicalutamide means that your cancer has become resistant to androgen ablation - whether it is to an anti-androgen or to an GnRH agonist - it is still resistant. That means the cancer does not depend on external androgens to activate the androgen receptor. It is likely that it still may respond to second-line therapy, as with darolutamide + lupron. There is no basis in fact for your belief that withholding ADT delays resistance. In fact, the opposite is probably true.

[CrocodileShoes in reply to Tall_Allen]

I guess what I meant by that statement was that -from what I've read-- ADT works for a specific period of time (although how long seems to vary) I'm not against going on Lupron et Al (although I am worried that I will not be able to continue working). Eventually, it stops being effective.. I know that. ADT is there for me. I am just trying to find strategies that can buy me more time, while my cancer is still classed as 'locally advanced', before the ADT becomes the only option.

People have written about the advantages of reduce tumour load that I am particularly keen on exploring that- without risking strictures, fistulas, etc.

Even though I've been on this journey for 10 years, there's still so much more to learn. So I'm especially grateful to this forum.

[Tall_Allen in reply to CrocodileShoes]

Lupron is still working when one is castration resistant. In fact, it becomes more important than ever then. Your goal is to increase survival with good QOL, not to just buy time while you are hormone sensitive. You seem to be focussed on the wrong thing. That ship has sailed anyway. There are many options available to to castration-resistant men; in fact, more options than for hormone sensitive men. You can look at it as an opportunity to use some powerful medicines than have ever been available to you up to this point to slow progression.

[CrocodileShoes in reply to Tall_Allen]

Thanks for the encouragement - it's what I need right now! I don't think I'd qualify for metastatic treatments yet, because there's no evidence of spread - either to lymph nodes or bone mets. But I will start the Lupron injections with possibly Daolutamide (if I can persuade my MO to prescribe)

Thanks for your advice.

[CrocodileShoes in reply to Tall_Allen]

Unfortunately, Darolutamide is not approved for use in the UK - a decision is expected in a year's time!

[GP24]

"I am worried that I will not be able to continue working" I had nine months of ADT with Degarelix and I could continue working during that time. The side effects of Lupron and Degarelix are very similar.

After six months I was fed up with ADT. However, my RO wanted me on lifelong ADT. So I just left him and decided to have intermittent ADT. The holiday has been three years now because I managed to keep the PSA value low with metastasis directed therapies.

If you stop Bicalutamide now, the PSA value may go down for a while. About 30% of the patients experience a Bicalutamide withdrawal effect.