Is a cure still possible post-RP?

[Blackpatch]

Hi

I had an RRP in Dec 17 after PSA of 15, clear PSMA scan... resulting in pT3b with G7=4+3 and 5% tertiary 5 with lymphovascular invasion. Negative margins and undetectable micro PSA at six weeks looked good, but 0.024 at 5 months and now 0.56 at 9 months - it’s coming back.

Given the negative margins and SVI, I have been told the chances for eSRT actually curing me are probably around 10% at best, and probably not worth the risk. That fits with the nomogram at pcnrv.blogspot.com/2016/08/ so I have been looking at re-purposed drugs (Care Oncology) to try to slow progression while I figure out what to do.

So I was surprised to read replies by Canoehead and Schwab this morning that seem to suggest people are talking about “cure” in the context of PCa that’s more advanced than where i’m currently at.

It sounds like there is a more aggressive school of thought that I am not tapping into via my current Melbourne-based team - have I read this right, or am I confused?

When I have asked about ADT it has been explained as a holding pattern approach, something that might last years but that would eventually fail and lead to later stage approaches - but you seem to be talking about ADT, in combination with some other drugs, that only lasts a couple of years and may lead to a possible “cure”.... have I misunderstood you??? If this is in prospect for oligometastatic guys, presumably it may also work for someone like me, who presumably has micro-mets only at this stage?

I would greatly value any advice you may care to offer, thank you...

Stuart

[Dayatatime]

Can anyone answer that question with certainty? No they cannot. However the one thing that is certain if you choose to listen to your current team you never will have a chance. Seek another opinion at a center of excellence. Do not wait because the lower the PSA the better chance you have at durable remission or cure. It will more than likely involve traveling but understand you have to put yourself in the best position possible. There are men on here that have beat the odds and almost all of them didn't do it by listening to one doctor's opinion. Don't let stats cloud your head either. We are all different and just because something didn't work for a "cohort" of others doesn't mean it won't work for you. No guarantees but definitely don't give up.

Ron

[Blackpatch in reply to Dayatatime]

Thanks Dayatatime - I am in the UK now to see CareOncology, and kind of thought I was dealing with the A team in Melbourne - but more than happy to go elsewhere for better advice, no problem...

Stuart

[Dayatatime in reply to Blackpatch]

The first specialist I went to see at a very well known treatment center told me they could do nothing for me. Between local hospitals and my first big hospital experience there were a total of 5 doctors telling me I would have to ride the HT train until it was over. I almost listened but gave it one more chance at Mayo in Rochester, MN. The good doctor I worked with there wasn't on the prostate treatment bandwagon so many others are and saved my life. Don't give up man. Push until all options are exhausted. You don't know what can happen along the way until you put yourself there.

[sedgley in reply to Blackpatch]

I do hope you are doing well!

How did you get on with Care Oncology in London? I guess I am asking if you were impressed and are you still using them?

Thanks.

[GP24]

As an alternative therapy to ADT there is metastasis directed therapy (MDT). This shall slow the progression of the tumor and delay the start of long-term ADT. If you are very lucky, this will delay for a very long time and you could call that "cure". MDT can be radiation of the mets or pelvic LND. Here is a recent review of MDT:

synapse.koreamed.org/Synaps...

In your case I would see Dr. Murphy:

twitter.com/declangmurphy

He did an MDT trial already but the results were not that exciting yet.

Dr. Emmett in Sydney recommends to radiate the prostate if the PSMA PET/CT does not show any mets:

snmmi.org/files/FileDownloa...

[E2-Guy in reply to GP24]

I have utmost respect for Dr. Declan Murphy. He is a great doctor and answers EVERY one of my emails within a day or two.

[Blackpatch in reply to GP24]

Hello GP24

And thank you for the paper on Australian SRT outcomes, which I had not seen.

My initial post said my PSA was now .56 but in fact I meant to type 0.056... and the window I see for making the eSRT decision is essentially the time it will take me to reach ca. 0.10.

The advice from my Melbourne team has been to have the PSMA “soon” and decide what to do then - this seems very much in line with Dr Emmett’s paper.

She doesn’t say much about the impact of concurrent ADT, which is a shame - and in fact the RO I have seen said he preferred that ADT come later, so the impact of the radiation could be assessed cleanly - but I have heard that the ADT acts to mop up

PCa cells damaged by the radiation and that ADT prior to radiation amplifies the radiation impact - so these are issues I will need to get to the bottom of fairly quickly.

The use of SBRT to tackle isolated mets is getting some attention in Melbourne - the paper you have attached on that topic is also interesting, but the short answer seems to be there is no real clarity yet on whether this approach actually delays progression.... I guess there will be more coming out in this area in the next year or two, given the number of places using SBRT in combination with PSMA to treat BCR.

Thank you again for your input

Stuart

[GP24 in reply to Blackpatch]

"the impact of the radiation could be assessed cleanly" - that's what my RO was thinking. However, the result of the radiation would have been better probably if ADT had been added. So what advantage do I have from a clean assessment of the radiation if it did not help a lot?

"ADT prior to radiation amplifies the radiation impact" there is no definite data to decide for this in the case of salvage radiation. All you can be sure of is that it will not make matters worse, it may improve the result of the radiation instead.

The Australian guidelines recommend to start SRT between 0.1 and 0.2 ng/ml. However, if you decide to start ADT before SRT, e.g. with Bicalutmide according to the study reported by Shipley, you will have a long window before you need to start with SRT.

thegreenjournal.com/article...

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

ascopost.com/issues/june-10...

[Blackpatch in reply to GP24]

Hi GP24

Thank you for this information - and yes, it’s all pretty confusing really - as these guys say, the slow progress of the disease contrasts with the rapid rate of change of treatment approaches and drug development, so it’s not really meaningful to expect to be able to ascertain “the best” course of treatment at any particular point in time.

And the additional availability of genetic information such as Decipher will only add to the complexity rather than simplify decision making, I suspect.

Right now, I am:

- trying non-hormonal off-label drugs like Metformin to slow PSA and buy time

- ditto a few “well known” supplements

- getting Decipher run

but unless something emerges from all the above, then I will be heading to ADT + eSRT after a further PSMA scan early next year....

... and the all while hoping that some of the trials using SBRT plus PSMA scans to zap individual recurrent sites, produces a definitive recommendation about that as a treatment option to lifelong ADT.

There seem to be a lot of other guys in much the same position - I predict someone is going to make a lot of money when they come up with an alternative to ADT that works...

Stuart

[GP24 in reply to Blackpatch]

Stuart,

if you would not use a micro PSA you would think your PSA value is undetectable. Most labs provide PSA values which start with 0.07 ng/ml. They provide no valid PSA values below that. So discussing the pros and cons of metastasis directed therapy can be postponed.

When I put your values into this calculator, assuming adjuvant ADT with SRT,

riskcalc.org/ProstateCancer...

I get a 5-year free from biochemical failure probability of 75% for you. So your situation, if your PSA value gets above 0.1 ng/ml, is a clear indication for SRT. If you suspect mets you can extend the radiation of the prostate bed, which is standard for SRT, to include the radiation of the lymphatic pathways. This should give you a 75% chance of cure for five years.

I know someone who decided to radiate the lymphatic pathways only. Now he has a recurrence in the prostate bed and thinks: why did I omit that?

[Blackpatch in reply to GP24]

Hello GP24

You’re certainly right about the use of micro PSA giving earlier cause for concern. But I found a Finnish paper that charts a large cohort of men from RRP onwards with micro PSA precision and their data showed that if a rising linear trend in Ln PSA data exists, it establishes early and persists through eventual BCR ... that’s what my data has done. I’m still in the UK so can’t easily reference the paper at the moment, but it’s a good piece of work.

The RO I consulted said he didn’t believe in doing SRT “above the waist line” so I don’t quite know how that fits with lymphatic targeting - but you’re right that the sort of cure odds spat out when you include a period of ADT make this something I will have to seriously consider in the next six months.

I am less clear how the Decipher data gets wound into that decision - if it comes back as low risk, for example, yet i’m clearly headed for BCR, it would seem kind of dumb to place faith in it never metastasising - if it comes back as high risk, then the case for radiation becomes clearer. I get the impression that Decipher isn’t too widely used in Australia so I may have to use a US or UK consultant to advise on this aspect.

Thanks again for your input.

Stuart

[GP24 in reply to Blackpatch]

So far you have just two PSA values. These are below 0.07 ng/ml. I would wait for at least two additional values before determining a trend and get six weeks of daily radiation done.

ROs should use a standard template to plan the radiation of the lymphatic pathways. At least the template is described in their books and mostly used for that purpose. This area is below "the waist line".

I consider a Decipher test result as one part of the entire picture only. The interpretation of the result is based on statistics provided by the manufacturer. If there would be different trials done, the results would be different to some extend.

[GP24 in reply to Blackpatch]

You mentioned a Finnish study, here is another one which suggests to start with SRT below 0.2 ng/ml:

ncbi.nlm.nih.gov/pubmed/284...

However, if there is no clear trend, the PSA value of many patients may stabilize below 0.4 ng/ml:

ncbi.nlm.nih.gov/pubmed/112...

FYI:

here is a discussion of the side effects of SRT. Adding pelvic radiation results in more side effects:

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

This article will give an overview of the existing literature and current controversies on: (I) timing of postoperative radiation; (II) use of concomitant androgen deprivation therapy; (III) optimal dose to the prostate bed; (IV) use of hypofractionation; (V) elective treatment of the pelvic lymph nodes; (VI) novel imaging modalities, and (VII) genomic biomarkers:

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

Dal Pra is a very good RO.

[pjoshea13]

When I was diagnosed there were two options that offered hopes of a cure - RP (radical prostatectomy) & radiation. Surgery offered better survival odds for my age & condition. Post-RP PSA was 0.3. No cure for me.

Salvage radiation was offered - but not with curative intent - but I went for it in spite of the morbidity. PSA went from 0.8 down to 0.3, but was back to 0.8 three months later.

In 6 months it will be 15 years since the RP. I have lived that long with the knowledge that I will never be cured. But at a very early point I set about investigating what might be done to manage the disease. Lupron was offered, but I didn't like the prospect of CRPC while still in my 50's. Not many options back then.

There are those who put their faith entirely in the hands of oncologists. Frankly, the life expectancy of someone with metastatic PCa was dismal 14 years ago & not a whole lot better today IMO.

I never sat around waiting for a large clinical trial before trying something with scientific basis behind it. IMO, the disease can be managed, but relying entirely on approved protocols might not be enough for most of us.

What has become very clear recently is that the newer drugs, which have a mean-time-to-failure that can be scary to younger men, lead to drug resistance involving cells that can be extremely difficult to manage.

With more drugs we have the possibility of more combinations & also an interest in earlier aggressive treatments. Personally, I am wary. Adding a couple of years to survival for a man with metastatic disease is a really big deal, but I always wanted more than that. My doctor thought I would be dead 7 years ago (he only mentioned that 2 years ago. I laughed & he said "No, seriously!". He is very supportive. I have an integrative medicine doctor who writes me prescriptions that my GP cannot. But even my GP is supportive. That is my team, but I do some research every day. Forget about "cure" (IMO) & think "management" - & get involved in the details.

Best, -Patrick

[Blackpatch in reply to pjoshea13]

Hello Patrick

I can relate to your wanting more time, and being prepared to look st alternative approaches in the face of progression post. RRP and SRT.

But I guess I don’t really understand what you mean by by an “ integrative medicine doctor”... is this what I have just accessed in the UK through CareOncology, with their Metformin etc protocol, or something else again?

Stuart

[pjoshea13 in reply to Blackpatch]

Stuart,

The "integrative" guys treat the entire person rather than the immediate ailment. While mine does not treat cancer, he does have many cancer patients. These doctors are more flexible in terms of treatments &, while mine uses otc products extensively, also prescribes drugs off-label. I have a few scripts from him that my GP would not prescribe.

-Patrick

[Tall_Allen]

I think you meant this link:

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

Or, it's easier to use this one:

riskcalc.org/ProstateCancer...

When I put in your numbers (I used GS 8 because of the tertiary pattern 5), it shows that your probability of freedom from biochemical failure is 71% at 5 years and 60% at 10 years. Those odds look pretty good to me. I don't know how you came up with the 10% number.

Given your tertiary 5 and your LVI, I think there is a good chance that cancer is in the pelvic lymph nodes, so I think you should consider whole pelvic radiation (at least 50 Gy) with a boost to the prostate bed (at least 70 Gy) with about 6 months of ADT, starting 2 months before salvage radiation (you can run it longer before starting SRT if you have not yet recovered full continence). Also see:

pcnrv.blogspot.com/2017/11/...

I think you have a reasonable chance at a cure.

[Blackpatch in reply to Tall_Allen]

Hello TA, and thank you

The nomogram link I meant to post was:

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

Using G8 as you suggest and a +66Gy dose plus ADT, I make the 10yr BCR-free chance 50%... the 10% I originally quoted was based on no ADT.

I will revisit the nomograms you have suggested with the RO, thank you. Do you have any reference for the length of ADT, since I haven’t seen eSRT ADT duration discussed elsewhere?

Stuart

[Tall_Allen]

Use the nomogram on the Cleveland Clinic website. Discuss ADT duration w your RO - there are many variables to consider. You may want to have a Decipher test to see what your probability of metastases is.

pcnrv.blogspot.com/2018/01/...