Revisiting the ORIOLE trial--SBRT vs Observation--Key Take Home points for the Oligometastatic PCa patient

[NPfisherman]

Hello FPC members,

After exchanging messages with another member, I wanted to review again the ORIOLE trial and some key analysis from that trial--the importance of utilizing a PSMA scan prior to treatment and genetic testing...to indicate potential benefits and eliminate missing lesions...PLEASE NOTE: this was a Phase 2 trial of 80 patients and more trials are needed..

The ORIOLE trial--analysis per JAMA network--please review graphs in article:

jamanetwork.com/journals/ja...

First, the use of PSMA scans to insure no undetectred lesions went untreated. From the study analysis:

The proportion of men with no untreated lesions with progression at 6 months was 1 of 19 (5%; 95% CI, 0-26.8) compared with 6 of 16 (38%; 95% CI, 18.5-61.5) for those with any untreated lesions (P = .03). The median PFS was unreached among participants with no untreated lesions vs 11.8 months among participants with any untreated lesions (HR, 0.26; 95% CI, 0.09-0.76; P = .006) (Figure 2C). The proportion of men who developed new metastatic lesions at 180 days was 3 of 19 (15.8%; 95% CI, 4.9-38.6) with no untreated lesions and 10 of 16 (62.5%; 95% CI, 38.5-81.5) with any untreated lesions (P = .006). Median distant metastasis–free survival was 29.0 months in men with no untreated lesions at baseline and 6.0 months in men with any untreated lesions at baseline (HR, 0.19; 95% CI, 0.07-0.54; P < .001) (Figure 2D; eResults in Supplement 2).

Second, the importance of genetic testing in evaluating possible outcome/benefit from SBRT... From the study analysis:

To avoid false negatives owing to undetectable ctDNA, we limited our analyses to participants with detectable ctDNA or truncating/pathogenic germline mutations in high-risk genes (n = 22). PFS was significantly longer among participants receiving SABR than among those in the observation arm in the high-risk mutation–negative subgroup (Figure 4B) but not in the high-risk mutation–positive subgroup (Figure 4C).

The key points for those oligometastatic patients is get a PSMA scan and genetic testing prior to having SBRT(if you chose SBRT). It will give you a better idea of what your expectations should be in doing SBRT. Feedback from Dr Tran at Johns Hopkins-trial organizer:

hopkinsmedicine.org/brady-u...

There are a number of individuals on these forums that went the harder route of ADT plus Zytiga with SBRT and the question remains as to how these people will do--Remissions of several years... Cures?? Time will tell... Dr. Tran mentions the RAVENS trial using Radium 223/Xofigo with SBRT in an effort to wipe out micrometastasis along with SBRT. This trial is still enrolling and worth considering for those interested.

clinicaltrials.gov/ct2/show...

Welcoming thoughts and feedback...

Don Pescado

[Hope59]

Thanks for posting!

[NPfisherman in reply to Hope59]

You're welcome..thanks for appreciating the post....I think that people who are oligometastatic need to realize there is a real benefit to SBRT and it is not just a "whack a mole" treatment... As per my statements, I am aware of 4 individuals that went the harder route of ADT plus Zytiga plus SBRT to lesions and some are at the 18 month mark and still progression free...Will it last longer?? My MO at Cleveland Clinic believes so...

Don Pescado

[6357axbz in reply to NPfisherman]

So is part of this process to stop ADT after SBRT to see what tumors may pop up next?

[NPfisherman in reply to 6357axbz]

Indeed, the people got SBRT or Observation and were switched off the trial depending on progression... I guess my thoughts are that if one is metastatic, then why not hit it hard at the get go and then take people off treatment and see... I know of one gentleman who followed a course similar to mine for 14 months and has been progression free for over 18 months. The ADT is hard and so why not combine for a period and then get a break...ADT is hard on the bones and heart... Continuous is a tough row to hoe as they say in the country...

Fish

[Break60]

After my psma ga68 scan in Oct 2018, I had SBRT in Dec 2018 to two bone lesions (scapula and a rib) found but switched to estradiol patches from an lhrh agonist (trelstar) in Feb 2019 to stop the side effects of "normal" ADT and have had no recurrences since. Fingers crossed!

[NPfisherman in reply to Break60]

Thanks for your input...Did you have genetic testing?? In the ORIOLE trial 5 genetic major mutations were screened for: BRCA 1/2, TP53, RB1, and ATM. I think Table 4(B) speaks volumes for those without high risk mutations... Given time, I believe there will be cures for the oligometastatic PCa patients. Are you still on the patches?? I took the harder route of ADT plus Zytiga with one lesion found by Axumin scan at PSA of 3... I guess I will find out over time...Praying on this one...

[Break60 in reply to NPfisherman]

Yes for Brca 1 and 2 : negative

[NPfisherman in reply to Break60]

Hey Break60,

I am unclear on your response. Were you positive for BRCA 1/2 or negative and did they test for the other mutations?? If positive for BRCA 1/2, then a PARP inhibitor should be in your treatment strategy.

Fish

[Break60 in reply to NPfisherman]

I thought I made it clear that I tested negative for those two genes. I didn’t test for others.

[NPfisherman in reply to Break60]

Best of luck to you on this journey...They are doing clinical trials on using estradiol versus GnRH agonists and I think if equal for T suppression then estradiol makes better sense....no brain fog, and eliminate the bone loss and heart effects... Man boobies are easier tolerated than osteoporosis, dementia, and myocardial infarctions...

[Break60 in reply to NPfisherman]

Agree 100%!

[6357axbz]

Really good post fish! Thank-you. I especially found Tran’s summary superb. An easy to read and understand summary of where things stand to date. Hopeful!

“The science is coming!”

[NPfisherman in reply to 6357axbz]

You're darn skippy... "The Science is Coming !!!" like a freight train down the tracks but sadly, some will not benefit... Hopeful indeed... I thought Tran's summary superb as well ...especially how oligometastatic condition is like an intersecting Venn diagram between local disease and metastatic... Thanks for the replies and compliment....

Fish

[cujoe in reply to NPfisherman]

The science IS coming and Don Pescado IS looking for it on our behalf. Thanks as always for you invaluable contribution to our patient knowledge base.

Stay Well - K9

[NPfisherman in reply to cujoe]

Thanks K9 Terror.... I do try and follow the science, but gosh darn it...the science is happening so fast... it is mind boggling....

Be well and take care...

Fish

[marnieg46]

A very interesting read Dave and although not relevant to Ron's situation this will be of interest to those who fit this category.

Once again you bring to your posts a rare ability to capture the essence of the scientific data, choose appropriate support references and then further the discussion by insightful, helpful and practical extensions drawn from your own personal knowledge and experience. And you do all this while making sure that the information you provide is easily discernible by those of us who might have less acumen to interpret the more complex scientific content by more straightforward explanations. A rare gift indeed and thank you for sharing. I always find what you post interesting. Keep on keeping on my friend... Marnie

[NPfisherman in reply to marnieg46]

Thank you, Marnie... I have seen people post about the ORIOLE trial but not specifically refer to these points. For those Oligometastatic patients that are considering SBRT, it is important to do the appropriate testing before doing the treatment. Leave no metastases untreated and do the genetic testing to see if you should be doing something else.. For those with a BRCA 1/2 mutation, the benefit of taking a PARP inhibitor after treatment should not be missed. I just don't want any oligometastatic PCa patients to do this in a half baked fashion. Do it and do it right... All the best to you and Ron...

Dave the Fish

[Break60 in reply to NPfisherman]

My RO who performed SBRT on my oligomets never even brought up the issue of a PARP inhibitor . Thankfully I didn’t have the BRCA mutation. Scary .

[NPfisherman in reply to Break60]

OK...all clear to me now.... Keep on keeping on.... it is great that many of us that did SBRT are cruising along well. Sad for so many others that found their cancers late... New drugs are coming and within 5 years, we should have several more...

Be well and take care,

Fish

[jdm3]

Thank you as always Fish. Great post.

I finally took the time to look at the study more carefully. If I understand it correctly, even those with a major mutation (like the P53) will benefit from SBRT. It seems like a no-brainer for anyone who is oligometastatic.

[NPfisherman in reply to jdm3]

Indeed, it would seem like a "no brainer" for anyone that has oligometastatic PCa. As long as treatment can be done safely, then why not. You are correct--even those with major mutations benefited from SBRT. When one considers that these people received SBRT alone, as opposed to our much more rigorous treatment plan, then my MO's statement that some will be cured using the rigorous strategy seems plausible.

Thanks for replying and all the best to you and Becky... Be safe and be well...

Fish

[GreenStreet]

Got on to this late. Thank v much for a v informative post

[NPfisherman in reply to GreenStreet]

You're welcome....I had SBRT early on despite negative feedback from some so called "expert" on these forums. Dr Tran and I were right .... Some still don't believe in the abscopal effect despite the ORIOLE trial...

Fish

[GreenStreet]

I might find myself in the position of considering it if I am fortunate enough to have that few mets. Had RP but PSA re occurrence followed by SRT to prostate bed only and 6 months of HT. PSA has risen steadily but relatively slowly from less than 0.01 to 0.07 this September. I am waiting for it to go up a bit more before looking to scan and locate. Not great but there you go.

[NPfisherman in reply to GreenStreet]

I do know they are looking at newer radiotracers, but at a PSA of 0.2, you can do the PSMA Pet/CT and may find the answer....at that point, you have options...best of luck....if your PSADT is 6 months or greater, then you have a bit of a wait....enjoy life...

[GreenStreet in reply to NPfisherman]

Thanks. Fortunately my PSADT is c 13 months at the moment which is not too bad. I take a load of supplements but discontinued them for 3 days prior to PSA test. I am based in UK and have a dilemma in that I might be able to get across to Nymegen where they can do a Combinex MRI which can pick up activity in lymph nodes at a lower PSA level from 0.1 upwards. So dilemma is whether to go to Nymegen c next March or April Covid permitting or wait for until possibly the following March if I am lucky for a PSMA scan at 0.2 upwards as I am currently enjoying not being treated. Lol. Really I know I should try and get earlier detection. Oligometastatic PC is an interesting area I am a bit concerned that more sensitive scanning will pick up more which means that less people will be classified with OPC and will make time series comparisons more difficult. But as you say the science is coming and we need to hang on in there long enough to benefit from it. Good luck to you too.

[NPfisherman in reply to GreenStreet]

Actually, the better PET/CT helps out on oligometastatic patients, because those that had all lesions treated based on the PSMA scans had less of a chance of relapse.... 13 months is much better than my 2 months PSADT, but I am on vacation too and liking it a lot...nice to feel normal again isn't it....

Fish

[GreenStreet in reply to NPfisherman]

Yes it is . Very good luck to you. Great point re identifying all the lesions.