Oligometastasic PCa

[pjoshea13]

New Canadian study below [1[.

Questions remain regarding oligometastatic (i.e. few mets) PCa. Is it curable with metastasis-directed treatment (MDT) alone? Does MDT improve survival?

Patients had "rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy."

"10 and 27 underwent surgery and SABR, respectively.

"Median follow-up was 15.9 months (IQR 9.8-19.1).

"... the overall response rate was 60%, including 22% rendered bNED {biochemical 'no evidence of disease'}."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/336...

ur Urol

. 2021 Mar 5;S0302-2838(21)00151-2. doi: 10.1016/j.eururo.2021.02.031. Online ahead of print.

Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis

Rachel M Glicksman 1 , Ur Metser 2 , Douglass Vines 3 , John Valliant 4 , Zhihui Liu 5 , Peter W Chung 3 , Robert G Bristow 6 , Antonio Finelli 7 , Robert Hamilton 7 , Neil E Fleshner 7 , Nathan Perlis 7 , Alexandre R Zlotta 7 , David Green 8 , Andrew Bayley 3 , Joelle Helou 3 , Srinivas Raman 3 , Girish Kulkarni 7 , Charles Catton 3 , Tony Lam 9 , Rosanna Chan 2 , Padraig Warde 3 , Mary Gospodarowicz 3 , David A Jaffray 10 , Alejandro Berlin 11

Affiliations collapse

Affiliations

1 University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada.

2 Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 263 McCaul Street, 4th floor, Toronto, Ontario, M5T 1W7, Canada.

3 University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

4 Centre for Probe Development and Commercialization, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4L8, Canada.

5 Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada.

6 Manchester Cancer Research Centre, University of Manchester, 555 Wilmslow Road, Manchester, M20 4GJ, United Kingdom.

7 Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

8 University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada; TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

9 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

10 TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada; Divisions of Radiation Oncology and Diagnostic Radiology, MD Anderson Cancer Centre, 1515 Holcombe Boulevard, Houston, Texas, 77030, United States.

11 University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada; TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. Electronic address: [e-mail].

PMID: 33685838 DOI: 10.1016/j.eururo.2021.02.031

Abstract

Background: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches.

Objective: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT).

Design/setting/participants: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible.

Interventions: All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT.

Outcome measurements/statistical analysis: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1.

Results: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed.

Conclusions: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa.

Patient summary: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Keywords: Metastasis directed treatment; Oligometastasis; PSMA PET; Prostate cancer; SABR.

Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[6357axbz]

Patrick, am I understanding correctly that a pre-condition for inclusion was radical prostatectomy and no one had RT to the prostate in lieu of RP?

[pjoshea13 in reply to 6357axbz]

The patients all had "radical prostatectomy and post-operative radiotherapy", which they categorized as "maximal local therapy".

Perhaps it was felt that this offered the best chance of proving the hypothesis that oligo-PCa could be cured?

-Patrick

[ragnar2020]

Hi Patrick,

Thanks for this. Those of us in the limbo of continuing care post primary treatment by either RP or RT awaiting eventual BCR and continuing to research what to do when the BCR occurs.

With what has now become inadequate imaging as we all await FDA approval of additional sites for PSMA-PET scans beyond UCLA, local treatment of mets would be welcome if the docs can find the mets.

Whether to include HT before, during or after BCR is a complicated open question of SEs and QOL. If we decide to begin HT, how do we choose the drugs to include? We’re dependent upon MOs, and they have their favorites and their institutional restrictions, so it makes for a complicated decision tree analysis.

Thanks again,

Jeff

[Justfor_ in reply to ragnar2020]

I am in the same situation as you, waiting for the PSA to rise to 0.2, so I will be scanned within a clinical trial already been accepted to. If not for this trial I would had already been scanned as my BCR is beyond any doubt. But, I was bought to the idea that it will be read by two experienced radiologists. My path is clear: Two weeks before scanning I will start taking Bicalutamide in the hope that it will stimulate PSMA excretion. Depending on the outcome of the PSMA PET/CT I will try to keep PSA low by continuing Bicalutamide until the initiation of the next treatment. The situation with COVID is another variable that will influence the timetable. Definitely not starting Luprolides or anything of such sort.

[ragnar2020 in reply to Justfor_]

Hi Justfor,

I’m curious if you’ve considered tE2 instead of traditional ADT drugs? Have you looked at the PATCH trail info? Are you getting your PSMA-PET at UCLA? What I’m wondering is if getting the scan before the mets have risen to .5 is useful for possible local treatment, or of one should delay the scan to avoid false positives?

Jeff

[Justfor_ in reply to ragnar2020]

Jeff, I am on the other side of the pond. I can have the PSMA PET/CT anytime I wanted by paying out of pocket 1500-1800 Euros. The Heidelberg spreadsheet gives me a probability for positive detection, now at PSA 0.15, ~60%. With ADT an extra 10%, elevating it to 66%. It is enough for me, surely higher than a blind early sRT.

If/when you see indications of BCR, DO NOT (repeat DO NOT) wait to reach 0.5.

Your best advisor will be your PSA doubling time. From your profile I saw that you take quarterly PSA tests. I do monthly, primarily using 2 different labs and a 3rd one when the offset between them becomes too high. Since RP (May 2019) I have taken 21 PSA tests, 2 of which were "gloriously" false. This is ~10% failure rate. Now, approaching the 0.2 mark I am shortening the period of PSA testing so that I will give the hospital the 0.2 report they demand at just this number.

[ragnar2020 in reply to Justfor_]

Hi Justfor..

Thanks for that advice. Yes, us gents in the States have been dancing around the delayed implementation of PSMA-PET scans for several years.

I had my RARP at MGH in 9/19 with a pre-op PSA of 4.9 and a Gleason 9/10 scoring. Post-surgery, I was categorized as pT3a NO EPE. The surgeon removed ten nodes, and there was no PCa found within them. But, there were two specs of PCa in the prostate bed too small to biopsy.

My last uPSA about six months ago was .014, and last week my uPSA was .034. The COE SOC facilities in the states where I've been treated are not fans of uPSA and they prefer the standard PSA tests. By those PSA standards, I'm still "undetectable," but we know that is a fantasy.

I'll take your advice and move to at least quarterly uPSA testing, and if the uPSA continues to rise, I'll move to monthly. It is doubtful that I'll get any encouragement at MGB for a PSMA-PET scan until the PSA is .5, and then if MGB is not offering the PSMA-PET scan, I'll be on my own. I can see this becoming a battle of "do what I recommend...... I'm your doctor." Presently, I have not selected an MO anyplace to monitor and oversee my treatment following the anticipated BCR.

My pre-BCR limbo continues.

Jeff

[Justfor_ in reply to ragnar2020]

My textbook exponential growth PSA curves

Dotted line is from PSA counts by LabA. Dashed, ditto by LabB. Solid line all 5 of them.

[NWLiving in reply to Justfor_]

Wow, Bills results look more like a series of increasingly larger mountains with peaks and valleys over the last year.

[Schwah in reply to ragnar2020]

I’m lost. What’s “uPSA” and how does it adjust from PSA?

[Break60 in reply to Schwah]

UPSA is ultra sensitive test to three decimal points. Like .192 vs .2 . I never saw the need except after prostatectomy.

Bob

[MateoBeach in reply to ragnar2020]

Wait a minute. . . You say no ECE on your RP pathology and yet “two small spots of PCa on the prostate bed”?For me

That would be sufficient to consult a good RO to discuss SRT to the prostate bed with fill pelvic LN fields included with a PSA that is not actually undetectable I would take no reassurance from that and would

act promptly for possible definitive treatment.

That is what I did in 2007 when my path showed tumor to margins. But they were not including the PLNs in the

Field In those days which would have helpe in retrospect.

[ragnar2020 in reply to MateoBeach]

Hi Paul,

We discussed this situation earlier, and I pursued the issue with the RO to whom I was assigned to at MGH and two other ROs at PBT facilities in FL and ÇA.

All three ROs believe that the presence of PCa in the margins following the RP did not warrant either SRT nor beginning ADT HT until the PSA moved to .2 as determined by uPSA. Hmmm? They all received copies of my pathology report.

I made the decision to coast until the BCR arrived as determined by uPSA. I believe that my body has my Gleason 9/10 PCa cells circulating within my lymphatic system, so SRT of the prostate bed to try and erase those two spots that were found by the pathologist following the RP would be premature treatment. Those spots may seed into tumors eventually, but I prefer to postpone the SEs of HT and RT as long as possible and maintain a QOL that is better.

Because I’m dealing with CAD dx in 2015 with five blockages within my heart, I don’t want to add complications from HT to my cardiac issues sooner than may be necessary. Of course, I could be wrong and I may regret this plan someday.

Jeff

[MateoBeach in reply to ragnar2020]

Thanks for the update Jeff neat of luck and am here for you.

[GP24 in reply to Justfor_]

Hi Justfor,

I do not know the Heidelberg spreadsheet, my orientation is this chart by Fendler below. I took Bicalutamide before my PSMA PET/CTs, but recently I read this study by Emmett which reports reduced sensitivity when hormone-sensitive patients get ADT before the PSMA PET/CT:

jnm.snmjournals.org/content...

Therefore I will not take Bicalutamide next time I will get a PSMA PET/CT. What is your source that reports an increase in uptake when taking Bicalutamide?

GP24

Sensitivity of PSMA PET/CT by Davis and Fendler

[Justfor_ in reply to GP24]

Hi GP24, We have discussed this in the past. No tangible evidence that Bicalutamide _temporarily_at_start_ increases PSMA. It's "cousin" Enzalutamide does, so there is a chance that they act similarly.

The Heidelberg paper is:

"Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT

in patients with recurrent prostate cancer: evaluation in 1007 patients" (2019)

I am using the coefficients of Table4, i.e. PSADT treated as a continuous variable.

Will check the link you posted although ADT has a very broad meaning (what substance and for how long before the scan).

PS

From the link you proposed:

Cohort 1: "luteinizing hormone-releasing hormone [LHRH]±bicalutamide"

It is evident that bicalutamide is not the prime player here, LHRH is and lowers T.

Cohort 2: "enzalutamide or abiraterone"

No LHRH here (no reason to lower T) as the patients are castrate-resistant.

Not a relevant paper for the subject discussed, IMO.

[GP24 in reply to Justfor_]

Well, it is a paper which was done to clinically determine the effect of starting ADT just before a PSMA PET/CT. There are not that many of these studies, maybe it is the only one. If you are convinced that only Enzalutamide or Bicalutamide will increase the SUV uptake, yes, it is not relevant. But there is only the observational study by Prof. Ezziddin which reports this effect with Enzalutamide.

I had a PSA value of 1.97 ng/ml and started Bicalutamide to increase the SUV for the following PSMA PET/CT. However, no lesions were found. So I will not add Bicalutamide next time and see what happens then.

[Justfor_ in reply to GP24]

Your argument sounds reasonable.

[MateoBeach in reply to Justfor_]

BTW. I was considering possible Lu-PSMA treatment as I expected metsOutside the pelvis, Before my first scan. So I did the first PSMA scan off

all HT to get a personal baseline if I had proceeded I would have repeats scan in Australia after priming with Enzalutamide to see if this enhanced my SUV max on any remaining lesions. Fortunately my scan showed only oligomets only in the pelvis best targeted by EBRT. Lutetium remains in the quiver.

[Break60 in reply to ragnar2020]

I waited for psa to climb near 2.0 to ensure an effective reading. I know that some consider that crazy but as I said UCSF required it at the time. So did the clinic where I got an Axumin scan in 2017.

[MateoBeach in reply to Justfor_]

It is a good plan IMO. Just wonder if bicalutamide is optimal choice to stimulate max PSMA expression. I know they are using and continuing to study enzalutamide in Australia for that purpose. But most patients are more advanced if not CR. I am HS and after 12 years of various approaches, still HS off ADT and BCR with PSA 0.25. Had PSMA scan at UCLA showing just two small avid PLNs no and nothing elsewhere. So I fit the profile of the study. Had hemipelvis RT with 4 months adjuvant ADT. Now off all treatment for 14months. PSA is 0.080 and drifting downward. Optimistic, but this study suggests only 20% chance of possible cure. Good luck brother.

[Justfor_ in reply to MateoBeach]

Excellent path you are strolling on (neither running or even walking). 12 years HS is something very reassuring for us newbies. Enzalutsmide is difficult to source over here and certainly not covered by the health care system in my personal case. Paying out of pocket entails a list price of about 2800 Euros, aka 3+k USD. Consequently, Bicalutamide will be the second best option.

[MateoBeach in reply to Justfor_]

Makes sense and may be shown one day to be just as good. I got a lot of mileage out of bicalutamide with dutasteride as alternative ADT so I very positive towards it even though it stopped working for me after 4+ years of control. That is priceless.

[MateoBeach in reply to Justfor_]

Oh, and yes my adjuvant ADT was mostly E2 patches with just One shot of Firmagon;120mg to get started. Felt GREAT on this vs conventional ADT

[Survivor1965 in reply to ragnar2020]

Hello Jeff,

Admittedly I have a hard time following a lot of what is posted here and I do not pretend to understand all that is going on within the PC treatments and imaging. However, I am confused when I read what you wrote about inadequate imaging. I have been under the impression that my C-11 Choline scans that I have been receiving are among the latest greatest scans for pinpointing early lesions. Also when I get MRI's every 3 months are they not adequate? Just need to understand this more.

Thanks, J

[ragnar2020 in reply to Survivor1965]

Hi Survivor,

IMO, you’ve been getting one of the better scans offered in the US, but it is not what is considered the most sensitive. The PSMA-PET scan detects some of the smallest mets within one’s body, but the PSMA-PET is only selectively offered in the US.

It is my understanding that the FDA has allowed UCLA to offer the PSMA-PET scan, but I’m not sure if Medicare or other US insurers will pay for the scan. The PSMA-PET has been widely available in the EU, GB and Australia, but not in the US - yet. The PSMA-PET scan can detect mets smaller than the other scans offered in the US.

If you ask your RO about the PSMA-PET scan, I think you’ll be told that they do not offer it yet, and you’ll be told that whatever scan they offer at that RO facility is just as good. IMO, this is not true, but no one wants to lose a patient who is willing to schedule a scan at UCLA, get on an airplane and go there. And, you’ll probably need to pay for the PSMA-PET scan yourself.

There are PSMA-PET scans offered as part of trials around the country, so a lot of gents have been able to qualify for those trials and have obtained the PSMA-PET scan in that manner.

Hope this simplistic explanation clarifies the PSMA-PET scan discussion a bit. BTW, I hope that by the time that I need to get a PSMA-PET scan, the FDA will have approved it for use at other COE centers around the country and those facilities will have begun to offer the scan as standard procedure for the PCa mets search for their patients.

Jeff

[Survivor1965 in reply to ragnar2020]

Thank you Jeff! Great explanation. At least I feel that Im getting something pretty good. I did not know the PSMA scan was more sensitive than my C11. I will ask my Onc when I see him on the 30th. I wonder where the Acumin scan falls in all of this?

And I wonder if what my onc says about as long as blood tests for me continue to fall in line, ie PSA, alk phos, etc that Im still in a good place. Kwon at Mayo told me that the guys that were the worse had no rising PSA.

[Break60 in reply to ragnar2020]

I see that FDA approved psma 11 ga68 at UC SF and UC LA . My psa needed to be 1.9 to get approval. Plus I had to be off ADT obviously to allow psa to climb! They found two bone Mets which I hit with SBRT back home. I had my scan at UCSF in October 2018 before FDA had approved it and paid nothing. Except of course air fare, hotel etc!

[Justfor_ in reply to Survivor1965]

Choline Vs PSMA is one of the endpoints of the trial I was accepted to. The second is whether they can find any correlation of the max SUV to the burden of the disease. Current understanding has it as the two being equal at high PSA counts. My low PSA combined with a medium to short doubling time gave me the ticket to this trial

[Break60 in reply to Survivor1965]

C11 choline WAS the best a few years ago but it’s been superseded by psma based scans.

[Survivor1965 in reply to Break60]

ok thanks! I didnt know that. Makes me a little nervous, having advanced disease and not getting the most up to date scans. Lately just MRI's because my PSA is still undetectable. Im gonna mention it to him. Many thanks

[Break60 in reply to Survivor1965]

Survivor

If you’re undetectable why are you worrying about scans? Relax! The best scans are most reliable at psa above 1.0 anyway. And the best closer to 2.0.

The really important thing is psa doubling time. Look that up on google.

Bob

[Survivor1965 in reply to Break60]

I don’t see where I said I was worried. I’ve beaten 2 life expectancy estimates as of today so I don’t see where wanting the latest greatest scans is unreasonable. In 2015 my C11 scan revealed 4 very small lesions on my spine/ribs. Doc set me up with cryoablasion and zapped those buggers before they became a problem. Did this twice in a year. Early detection is huge.Also my doc told me in some advanced cases tumors grow with little or no PSA rise. So I don’t really understand your post. Are you suggesting blood work only Bob?

[pjoshea13 in reply to Survivor1965]

It wasn't that long ago that doctors felt that it was pointless to treat mets (unless for pain.) I still remember being told "If you have one, you have a lot - you just can't see them."

The radio-oncologist who treated my L5 was sceptical regarding a survival advantage. Five years later, my survival without widespread mets turned him into a believer.

Your situation was dire ten years ago, yet here you are! Seems like it may have been a good idea to zap those lesions.

Best, -Patrick

[Break60 in reply to Survivor1965]

Yes quarterly blood work will tell you if you have a fast rising psa which would dictate a scan. Plus it’s easier on your body than scans.

[GP24]

I agree with Dr. Palma, who did the COMET trial radiating oligometatases. He says: SBRT of oligometastases is not curative. As you can see from this graph based on the COMET trial that about 30% of the patients treated with SBRT recur within six months. Only a few have no recurrence after five years.

Result from COMET trial

[Break60 in reply to GP24]

If you have aggressive Pca it’s in your blood but microscopic which is why systemic treatment is necessary to keep them from growing into man killers. I know that SBRT to visible ( by effective imaging) oligomets is not proven to be effective but I’ve done it twice in 2017 for one bone met and 2018 for two bone mets and I don’t regret it. I tried intermittent ADT but it didn’t work.

[GP24]

But he asks, would you be interested in a drug which halts tumor progression for one year? This would be a home run, most drugs are approved because they show a benefit in overall survival of three months.

From my own experience I agree that zapping oligometastases with SBRT can provide about a year of no tumor progression without ADT. So this would be about the effect of the hypothetical drug which Dr. Palma mentions. So radiating oligometastases can be beneficial even if not curative.

Slide by Dr. Palma

[cesces]

" 22% rendered bNED {biochemical 'no evidence of disease'}."

I think the question unanswered is, is this good or good enough compared with global treatments.

Without that arm, it would seem to me sort of a wasted trial.

It seems like it was designed to affirm a pre-existing commitment to a point of view, as seems to be the current rage among many people now adays.

I didn't check, but I will hazard a guess this study was designed by radiation oncologists.

A properly designed study would have included some global therapies.

Such a study would then be truly helpful to patients making informed treatment treatment decisions.

[pjoshea13 in reply to cesces]

22% had no biochemical evidence of disease after a median follow-up of 15.9 months.

i.e. a significant percentage had a possible cure - & if none turn out to have been cured, they would at least have had a nice long vacation from the morbidity of standard care.

That's pretty good for metastatic PCa IMO. Sign me up.

The study did not have to prove anything else, since we would not expect conventional AR-axis-targeted treatment to be curative.

They set out to validate "The hypothesis of a curable oligometastatic prostate cancer". Short of prolonging the study until everyone was dead, I think they achieved that.

[cesces in reply to pjoshea13]

The issue is compared to what.

That's why a placebo arm is de rigor for FDA studies.

If the purpose of the study is to compare treatments, it's missing something, isn't it.

[Blackpatch in reply to cesces]

Not just “compared to what?”, but “for how long?”

I don’t understand how BNED has any meaning if it recurs a few years later, and all the MDT studies i’ve Seen either indicate it does recur, or have been done over short periods.

[cesces in reply to Blackpatch]

Blackpatch

"Not just “compared to what?”, but “for how long?”"

Please elucidate. I am not certain I understand.

[Blackpatch in reply to cesces]

Hi Cesces

What I mean is that if the BNED turns into recurrence after 6 months or similar, then it clearly hasn’t been a genuine measure of “no evidence of disease” - the disease has been there, it just hasn’t been at a detectable level.

Stuart

[cesces in reply to Blackpatch]

Oh, you mean the concept of "curative" is flawed and misleading.

All you can say is, "no evidence after the passage of X period of time."

And you can't discuss cure without discussing the time variable.

Do I have that right?

[MateoBeach in reply to pjoshea13]

👍🏼 Exactly. Most do not know how much harder, resource intensive and expensive it would be to do with a control arm. This sets a reasonable baseline. Longer term follow up will show the durability of the nbED.

[cesces in reply to MateoBeach]

"Most do not know how much harder, resource intensive"

This was two arms. Just the wrong two arms. The two arms selected sort of guaranteed a result of economic benefit and justification of radiation by more prospective patients.

The real choice is not between two types of local therapy, but local vs global.

[GreenStreet]

What about SBRT followed by a year of ADT? Could that work or just delay? Still maybe worth while. I expect to be scanned this summer . Depends on next PSA test late March.

[Hidden in reply to GreenStreet]

My husband is in that study - PR 20 Platon

[MateoBeach in reply to GreenStreet]

Yes. If the PSMA scan shows no disease outside of the pelvis then that wouldBe the way to go. Extended field SRT rather than oligomet directed Tx if elsewhere.

[Hidden]

What does Tall Allan 🤔?

[ZCorn]

Hi PJ: I feel a bit unsophisticated when reading your posts, but I get the gist. You post interested me because, I was diagnosed in Jan 2019 with PSA 289 and Gleason about 7-8. After 3-4 months of Lupron/Zytiga/Prednisone, my PSA went to and has stayed at undetectable. I am now seen by UCSF doctors after moving from Kaiser. The question I'm pondering is "Do I do radiation now, while the cancer is at low activity, or, wait until PSA begins to rise." Kind of the age old question - invest now and have fewer fallback alternatives or keep powder dry until needed. Thoughts? NOTE: The docs, so far, have suggested a 150 gray dose to prostate for (1) 20-day cycle.

[pjoshea13 in reply to ZCorn]

You had mets in ribs? With PSA undetectable, would they show up in a scan these days? Can't treat what you can't see.

I can't speak to the suggestion of radiating the prostate at this point. I confess to a bias for surgical removal. Either way, oligometastatic treatment would encompass the prostate & the two mets.

Best, -Patrick

[ZCorn in reply to pjoshea13]

Thx PJ

[cesces in reply to ZCorn]

""Do I do radiation now, while the cancer is at low activity, or, wait until PSA begins to rise."

There is generally applicable statistical research that indicates when dealing with adaptive entities, you are best off going in hard and early.

This research has informed much current cancer treatment.

It's also applicable to optimal response to pandemics. World wide, the countries that have successfully fought Covid have followed this science. Australia, New Zealand, Korea, Taiwan, Japan.

The countries that have tried to balance and moderate a response are the ones that have been shut down by the "metastasis" of Covid.

This is why modernly, ADT is now frequently a cocktail of drugs instead of a stepped escalation, as the insurance companies used to require.

[treedown in reply to ZCorn]

I did radiation 3 months after starting Lupron in Oct 2019. It was done with curative intent and I am to stop meds this Wed since my latest PSA dropped from <.1 in June to <.04 today. I assumed the test at Quest would not go below <.1 so I was surprised when it came in that much lower. I received radiation up to the aortic bifurcation, 80 gy over 44 treatments.

[Karmaji]

Confusion about Oligo metastasis ...My question remains unanswered and contradictory response from Onco RO Uro...Is it curable ?

I had 2 tiny spots on pelvis..GL 8 PSA 30 May 2019

Went on ADT and RT with radiation of tiny spots in Nov 2019

Just after had Choline pet scan ...no trace on pelvis...sure ADT may hide it..

My questions are :

How long to stay on ADT ..I am on for about 2 years... Docs recommend 3 years before vacation

Since a year psa < 0.006

How to know if one is cured... if at all

What are markers ?

Docs say only marker is PSA after vacation

In effect, I get the impression that I am never cured ..only in remission...

then question is what are the markers for recurrence besides rising psa

Thanks to all...

[ragnar2020 in reply to Karmaji]

Hello Karmaji,

It is my non-medical opinion from a lot of reading - see Anthony Horan’s book - that once definitively dx with PCa, you have PCa forever. Various treatment of the gland whether it be surgery, radiation or HT slows down the progression. PCa is not a curable disease - yet. It is chronic, and the treatments that we use prolongs our lives balanced against Ses and QOL.

Jeff

[Karmaji in reply to ragnar2020]

Thanks Jeff everything is chronic anyway and it becomes normal

[Karmaji in reply to Karmaji]

Very sad Anthony left on a no return journey on Aug 13 2020....c est la vie

[Break60 in reply to ragnar2020]

Jeff

From what I’ve seen (as a Gleason 4/5 patient) speaking with my colleagues who’ve had Pca with no recurrence for decades after initial treatment (be it surgery, seeds , whatever, )a cure is possible with low risk Pca which is caught before it spreads beyond the prostate organ. Makes intuitive sense. And Gleason score has a huge influence on spread. I’ve had three oligomets imaged with either Axumin (femur) or Ga68 psma ( scapula and rib) treated with high dose SBRT ( which continues to be controversial with regard to efficacy) and I’m on permanent HT with estradiol. I’ll never be cured but I’m living life while continuing the fight daily as are many , many other guys with aggressive Pca.

I consider myself fortunate compared to guys with significant metastasis. Bob

[ragnar2020 in reply to Break60]

Hi Bob,

Like you, I have several friends and new associates in the PCa adventure who have survived as long as twenty years after dx and then primary treatment of their prostate.

I believe, but cannot prove, that most guys begin their PCa disease progression during their second or third decades, and depending upon the aggressiveness of their PCa, their disease progresses for about fifty years. If they intervene with RP, RT or HT, they extend their lives before death from the disease. A good percentage of men with PCa will die from another ailment before PCa kills them, and we know that depends on the aggressiveness of their type of PCa.

It sounds like you have been proceeding with your disease variant the way I hope to be able to handle my own care. I chose to have a RARP, and it went well with no serious SEs that I did not anticipate or was warned might occur. My Gleason score of 9/10 isn’t favorable for me not to experience BCR, so I just hope that I get as many years as possible before the second act of my PCa treatment(s).

I foresee the use of tE2 for ADT HT and PBT for SRT eventually when a PSMA-PET identifies the mets after BCR, and then local PBT zaps them. This may be wishful thinking and simplistic logic, but it is what I have right now. Keep up your plan. It sounds as if it is working.

Jeff

[Break60 in reply to ragnar2020]

Jeff

I was told by my surgeon at John’s Hopkins that Pca takes about 10 years to show up as a sharp increase in psa.( ie increased psa velocity). That’s when biopsy and tx become necessary. That’s why it’s important to get a psa test annually imho. Given that I was Gleason 9(4+5) at Dx it could be that less aggressive Gleason scores could take longer to “ show up” if ever.

Bob

[noahware in reply to Break60]

"a cure is possible with low risk Pca which is caught before it spreads beyond the prostate"

The question that was brought up decades ago* is this: if the PC is low enough risk, is cure even needed, and if cure is actually needed (because the PC is high enough risk), is it truly possible?

We know that a huge number of cancers of the LOWEST risk are indolent and need no cure, because they are not lethal. Men would have died WITH them without ever having known they existed. Yet, when discovered and treated, these indolent case are chalked up as being "cured" by the treatment!

We also know that many cancers of the higher risk category can be treated locally to no avail in the long term, because they were never actually curable in the first place.

Anthony Horan asserted that by the time PC can be clinically identified by DRE or biopsy, it has nearly ALWAYS spread beyond the prostate organ, if only microscopically and in a manner and at a level that may be neither detectable nor destined to be clinically significant. So we have to ask: should metastatic cancer that is not clinically significant or detectable, but does in fact exist, still be considered "metastatic?"

Because it seems that if the technology to find it existed and was deployed, it WOULD be found. Most micro-metastases are NOT found, because we simply can't see them with standard scans.

*[Willet Whitmore’s adage on the efficacy of radical prostatectomy, more or less: when an operation is necessary it is not possible and when possible, not necessary.]

[ragnar2020 in reply to noahware]

I endorse wholeheartedly Noah’s discussion about Anthony Horan’s opinions concerning PCa presented in his book. I read Horan’s book several times, and then, I read the memoirs of the PCa survivors whom he discusses within his book. Then, I contact Dr. Horan directly, and we communicated via email. He was an original thinker about the disease, and he took positions that were contrary to many of his colleagues within the PCa treatment community.

In summary, Horan felt that once diagnosed with PCa, a man has the disease and it is not curable. Depending upon the severity and aggressiveness of the PCa within a man, a man may live with his PCa and die from another ailment and his particular PCa will not kill him. Horan’s primary question was should all PCa be treated with RP, RT or HT if the PCa cannot be eliminated and it is not severe enough to cause death?

Horan felt that RP, RT and HT may add a number of years to the life of a man with PCa, but the SEs of the treatments may be adverse to the long term benefit of the man’s quality of life. Anyone can imagine how Horan would have been greeted as an alien at medical conventions where presentations were being done about advances found in surgery, radiation and hormone therapy for PCa.

Horan’s book should be read by every guy with PCa before he makes treatment decisions. When Dr.Horan died, we lost an advocate for us all.

Jeff

[jdm3 in reply to ragnar2020]

Jeff:

Not disagreeing with you and I'm certainly no expert, but a lot of data and information that are available to us on treatment outcomes is based on lagging indicators... a trailing average. There are better scans and new treatments in the last few years that seem to be moving the needle towards "cure" or at least long-term progression-free survival. I like to think (maybe a false rationalization or illusion of validity) some of the new data are suggesting oligometastatic PCa is curable if treated aggressively. Of course, it varies by individual, but the paper referenced in the original post here as well as other data, discussions, and anecdotal evidence give me hope.

[MateoBeach in reply to Karmaji]

If it were me I would be Stop the ADT at two years and let T recover and PSA reveal itself. If it goes up, BCR, then get a PSMA scan and see what may be left and where. Once you go on long term ADT CR is inevitable.

[Karmaji in reply to MateoBeach]

Personally I agree. But my URO and Onco stick to 3 years....RO is cool..he says why notyou can always come back....

This week I will have the opinion of another ONCO.

Over here they go for Choline Pet scan

[MateoBeach in reply to Karmaji]

👍🏼

[Break60 in reply to MateoBeach]

I was on IADT for 13 months at a time but my psa doubled very quickly each time I got off it which led to imaging and SBRT of the oligo bone mets. So I know I must be on some sort of ADT for life, and for the last two years its been estradiol patches because they're so much less abhorrent than LHRH agonists. My psa had been <.1 for two years but the last test in late Feb came out at .2 so I'm vigilante again. And for the last year or so I've had stress incontinence for which I had SLING surgery a few weeks ago. It's better but I still need to wear a pad and when golfing, I need to change it after nine holes because swinging a club still causes me to pee. Such is life on the Pca train.😅

[Northcaptain]

Thanks Patrick for posting it, i will bring to my onco attention at the next rendez-vous and maybe surprise him. That raise a question, what are the remaining option treatment after someone receive [18F]DCFPyL PET-MR/CT and get recurrence. Still the same HT track ?

[Break60]

Patrick

Has the imaging used in this study received FDA approval ( ie is it covered by insurance) , where can one go to get this scan and what level of psa is required for it to be effective?

Thanks

Bob

[pjoshea13 in reply to Break60]

Bob,

See ragnar2020's response to Survivor1965, above.

-Patrick

[Break60 in reply to pjoshea13]

See my response to Jeff re: psma FDA approval

[ragnar2020]

Hello Y’all,

This has turned out to be one of the more informative discussions about BCR, what treatment protocol to follow when BCR occurs, and the types of scans that are available to guys when the BCR treatment is needed plus a lot of other related topics. Good work, guys.

Elsewhere on HU, we find discussions in more detail about SRT, what type of RT to use - IMRT, SMRT, or PBT, and whether to mix in HT for ADT and when. We hear about SEs from HT. What drugs to use and when is discussed in more detail elsewhere on HU.

I’d like to see more discussion about specific ROs and MOs and where these docs practice and who they are. I’d like to learn more about which ROs favor what form of RT and why and which MOs will use tE2 for ADT and if not why? It would be helpful to know which MOs will use BAT for ADT.

A discussion about which scans are available, where, how frequently and how the instituions providing the scans expect to get paid would be informative when we’re considering treatment following BCR.

There is so much to learn so we can be informed recipients of our health care treatment for PCa and not feel like sheep being herded into categories of the SOC line-up of treatments without clear explanations about why one treatment is being recommended and not another.

But, of course, this is because I want these answers and maybe others on HU place more faith in their care givers and their knowledge and their reasons for what they recommend than I do.

Onward,

Jeff