Post RT decisions on ADT and relative risk benefit

[SimMartin]

apologies for long ramble again …

Next month I discuss how long to stay on HT (zoladex) after RT last December. I can feel like dealing with some multi headed hydra trying to balance risks/benefits especially as I have G9 (albeit maybe locally contained) and my personal comorbidities.

 As I reflect and read the research, I thought I could gather your views and comments as this might help in my decision process. To say ‘nothing is certain’ is perhaps an understatement with this cancer which can go AWOL and surprise us just as we’re getting our heads around living with it. As many say it becomes a chronic illness in many ways.

I was initially on AS for around 2 years, constantly being reassured it was low intermediate risk. However the PSA doubled, HIFU seemed a reasonable option for one sided twice biopsied as G7 disease. I thought it might give me another 3-5 years before more was needed. It turned out it didn’t and I end up with G9, RT and HT.

January 2020

Diagnosed after my annual PSA (I had one annually for over 10 years). It was 4.1 but I knew it had doubled in 18 months and I had an MpMRI and a Biopsy in January 2020 Of the 9 cores from three sites, only one site in one side was positive for PCa with G7 3+4 (<5% 4). I was put on AS with 3 monthly PSA which stayed around 4.5 – 5 for 18 months

July 2021,  

PSA rose to 6.2 - another MpMRI and biopsy now  2 sites but same side G7 3+4 (<5% 4) and G7 3+4 (<10% 4) - decide to try HIFU. 

December 2021

 rising PSA goes to 8 – but pre HIFU MpMRI shows no change from before and very suitable for HIFU. July 20223 months post HIFU PSA 5 and then 3 months later PSA 6.9Quite a shock as after another MpMRI and another biopsy diagnosed advanced localised G9 4+5 (4-70%, 3-20%, 5-10%) at edge of HIFU treated area and another site now new on the other side is showing G7 3+4 (<20% 4). 

August 2022

The urologist looked genuinely surprised and in one if those ‘breaking bad news’ consultations, said it’s very unusual. I am referred to Oncology the next day and and was out on Bicalutimide 150mg daily immediately. 

PSMA scan - no spread, locally contained (well as far as the technology can tell). I am offered just HT as i have other comorbidities and am 72, or RT and ADT with curative intent still (though I’m a bit sceptical now on how real that is with G9).

In discussion we opt for RT and on Zoladex monthly in October 2022 to treat with Moderately hypofractionated EBRT - 60Gy (20x3Gy) plus 6 months zoladex and then to assess whether to stop HT at 6 months. 

My internal discussion is, well it may actually be contained and caught early enough as it turned into aggressive and perhaps the PSMA negative scan is right (albeit we know it’s only 80%) and even if not ‘cured’ may be put in remission for many years. But then maybe all the other biopsies just missed it and it been there all along as the infield post HIFU recurrence is after all 70% 4 and 10% 5 and so was it always aggressive from the start. 

But ultimately does any of that matter now? Is it just a balance of what to expect with a typical G9 and negative PSMA and what the actual margin benefit is with longer ADT over 10 years anyway?

answers on a card to….. LOL 

[Tall_Allen]

I think 6 months of Zoladex is too little. You have a high probability of occult pelvic lymph node metastases (i.e., too small to show up on PSMA PET scans). And you cannot stop after 6 months and reassess - that would select for the most resistant strains of cancer. The relevant trial was called POP-RT. They chose patients with very high risk features like yours and gave them whole pelvic radiation and 2 years of ADT. 95% had no evidence of disease 5 years later. It was pretty spectacular.

prostatecancer.news/2021/08...

[SimMartin in reply to Tall_Allen]

of course the situation for me is in a way caste as it was decided NOT to include pelvic radiation, largely based on risk of side effects and the PSMA - admittedly as you say rightly G9 as it’s high risk tends to have increased risk of undetectable micro spread. That I ‘assume’ is the role of the longer ADT regime.

Though my struggle to grasp the actual biology and mechanisms of whether and how the ADT actually destroys the micro spread or just delays if the primary RT and or chemo hasn’t wiped it out.

Of course i maybe clutching at hopefuls (naturally!) without ignoring the reality of what my particular options are given my polio weakened muscles. The thing about the POP-RT study is that though they say some were PSMA scanned I could see how many and who was selected for PSMA and on what criteria. They used mostly it seems used the Roach formula to grade risk in the two arms of the study. Admittedly the Roach has proven pretty good as a quick and cheaper clinical tool to plan treatment but the extra (albeit not perfect at all) detection of the PSMA may change the decision on a case by case basis.

Also though the results are impressive for such a study if I look at my high risk stage being T2c / that is kind of in the grey area between high and very high and I couldn’t quite tease out the results for this sun group as the figures are given in terms of the PORT vs the WPRT group. It maybe there but as I say maybe, as was the WC Fields when as an ardent atheist is seen reading the bible in his lay days …. Ask why, says ‘oh! I’m just looking for loopholes’

Given all that and not having the pelvic radiation I will give more weight to considering staying with the ADT for longer.

[Tall_Allen in reply to SimMartin]

The Roach formula is better for this purpose than a PSMA PET scan. PET scans cannot find any microscopic (under 4 mm) metastases. Murthy only used the PSMA PET/CT to rule out distant metastases. Men who had distant metastases were not allowed in the study.

[maley2711]

It seems the more aggressive the treatment, the better the odds of a good longer-term result...but that does not mean that the less aggressive path will not work for any given man. I recently saw a single institution study of 30 high risk men treated with modern higher dose radiation....none of the men had any ADT, and the 5 yr results were something like 87% recurrence free over 5 years. The authors suggested that most studies pointing to substantial benefit of long-term ADT in combo with radiation were studies in which men received less than today's SOC dose. Seems you have done quite a bit of research.... have you reviewed more recent studies comparing duration of ADT when 78 GY or higher RTis used ??

[PSAed in reply to maley2711]

I had....as you said...78Gys over 39 fractions, my PSA has been undetectable for the 2 years since treatment started , my GS 4+3, T3aN1M0 and PSA @ Dx was 17. I finished Lupron last June '22 and will be having my next Blood test in April....6 months since my last. I hope I get the same results as the RCT TA linked.

Forgot to mention I had Whole Prostate Radiation.

[cancerfox]

I had a similar situation with G9 PC with no known spread. I was treated with 25 IMRT plus LDBrachy and 13 months of ADT. They told me I could have the shorter ADT since I did the brachytherapy instead of an additional 20 radiation sessions, so I think I would have had at least 18 months of ADT if I had just done RT. I'm no expert on PC, but I would have been a little apprehensive about doing RT and just 6 months ADT, even though ADT is pretty miserable. 🦊

[SimMartin in reply to cancerfox]

thanks yes - I am somewhat dubious about stopping at 6 months - but I think they may decide on how I report the side effects.

Also I had 20 session but was higher dose at 3Gys each time and told this is equivalent to the more sessions with the lower Gy dose at each session.

I DO have some co-morbidities as wheelchair user as very low muscle mass if I go out of my flat and also use breathing machine at night for the last 25 years due to weak breathing muscles NOT lung disease - I think my situation freaks them out a bit - lol - the problem is either they under treat for fear of side effects or they totally ignore my polio and just dole out standard treatment.

My current Oncologist is probably in the middle and very good at listening but as in all this how I report my side effects is probably critical to the advice given.

In fact the ADT isn’t terrible - but only done 5 months so far and I hear the side effects and cardio risk accelerate after 6 months.

[cancerfox in reply to SimMartin]

Polio definitely complicates the analysis. On the other hand, maybe you can't lose what you don't have. I thought I noticed considerable loss in strength after only 3 months, while you are saying 5 months hasn't been terrible. Possibly monitoring your muscle mass somehow while on ADT is the answer. I hope you come up with a viable solution. 🦊

[SimMartin in reply to cancerfox]

yes I had wondered about that - I already have fatigue and muscle aches as kind of normal for many years - and gradual muscle loss due to ageing with polio.

I did actually pay to have a body composition DEXA scan in December to get a base line of lean muscle mass. I can repeat that to see if there is faster loss. As it is mine is 13% which compares with around 35% for the average 70s make.

All a balance and a bit of guess work.

[RMontana]

Here is an article that says the genomic test from Decipher can help determine which men will/ can benefit from ADT and which cant. I would have my Dr's' look over my matrix results from a Decipher test to see if I would be wasting my time taking HT.

healthunlocked.com/active-s...

Here are some other articles on the benies of ADT post RT and or RP...these may help.

healthunlocked.com/active-s....

healthunlocked.com/active-s...

healthunlocked.com/active-s...

I took ADT Lupron for 6 months pre RT, and post RP, then for 15 months post RT...I am not off ADT start of Dec22...waiting to see what happens with my PSA...hopefully nothing. Good luck. Advise how things turn out. TNX

[SimMartin in reply to RMontana]

I am unclear if Genomic testing like decipher can be done in my core needle biopsies of G9 from last July? (Or the other two biopsy in Jan 2020 and July 2021 even though they grades G7 low intermediate) Are they suitable now (assuming they are kept) and if the storage system degrades the samples? Also I see Decipher mentioned more on radical prostatectomy where they have the whole gland.

I am bringing this up with my oncologist next week but would like to be armed with the facts myself first !

[RMontana in reply to SimMartin]

Check it out but your facility must store your biopsy samples for some years; that I know of yes this can be done. Listen to the entire podcast; Decipher's best trait in SOC is now seen as determining which men can even benefit from ADT...that is huge. If you genetically get no benefit why take it! So check all this out for sure and advise...I did it becaue my Decipher was off-the-charts bad, 0.97 out of 1.0...I had a lethal cancer type even with a GS 4+3...my Dr stated that to be comparable my Decipher should have come back between 0.5-0.6...it did not and I hit with very thing I could throw at it...wish I had known though about Deciphers predictive benefits on whether I would get any help from ADT...too late for me. Not for all you out there...why we do this site. TNX