Oligometastatic PCa has been controversial from the start, with some denying that it exists. "If you have one met, you have many - you just can't see them."
Then there is the counting problem. One study indicated that a few spinal mets visible on a bone scan were oligometastatic, even if another type of scan were to find more.
This influenced my thinking when I had a solitary lesion at L5 ten years ago. My doctor sent me to a radio-oncologist who might agree to ratiate. The man warned me that there was no data to suggest a survival benefit. He did agree to treat L5 - he would not have treated two lesions. (My regular doctor was surprised that I had been treated, because I was not in pain.)
When I returned 4 years later, his view had changed. He hadn't expected me to be alive. He said that he would now be prepared to treat multiple lesions because I was proof of concept that there might be survival benefit.
Mostly, men interested in oligometastatic treatment are hoping for a cure. I'm inclined to view treatment in terms of management. L5 wasn't being controlled by my current protocol - albeit that it was growing very slowly. I would wory about other mets, if they occurred, only when they became big enough to be of concern.
"The term “oligometastatic prostate cancer” refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the “better‐than‐expected,” retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate‐specific membrane antigen‐targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk‐stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis‐directed therapy, future efforts should focus on conducting high‐quality, prospective trials with much‐needed molecular correlative studies."
... from the Intro ...
"Metastasis has been conceptualized on a scale ranging from sequential, echelon‐level spread to de facto, widespread dissemination. More recently, a paradigm shift was prompted by Weichselbaum and Hellman, who hypothesized the existence of an oligometastatic state. Their assertion that a subset of metastases may be limited in number and location has since been both the subject of criticism and the inspiration for pioneering clinical trials investigating local ablative therapy for tumors that previously would have been treated with solely systemic approaches. Acceptance of an oligometastatic paradigm with the resultant impact on treatment recommendations is poised to potentially change the landscape of prostate cancer management, given evidence suggesting that as much as 75% of patients with recurrence after primary therapy will have ≤3 involved sites."
...
Conclusion
The term “oligometastatic prostate cancer” currently refers to a heterogeneous group of clinically defined disease states, including oligorecurrence and de novo oligometastases. Commonly used features to distinguish such individuals with limited metastatic disease include the absolute number of lesions (e.g., ≤5 metastases) and, less frequently, caveats like lesion location. This reliance on clinical features for case definition necessarily makes investigation into superior imaging modalities for the detection of prostate cancer oligometastases of considerable import. To this end, PSMA‐targeted functional imaging currently has the greatest promise, and its inclusion as part of the prospective ORIOLE randomized, phase 2 trial in the oligorecurrent setting should provide further insights into its utility. While awaiting the results from this and other protocols currently registered on clinicaltrials.gov for patients with oligometastatic prostate cancer, evidence from a disparate group of previously published outcomes suggests that an oligometastatic state likely exists for at least a subset of patients with prostate cancer. The most convincing testament to this possibility comes from the groundbreaking phase 2 trial in the oligorecurrent setting published by Ost et al, in which individuals in both the surveillance and metastasis‐directed therapy arms had higher than expected rates of ADT avoidance. Nevertheless, the appropriateness of metastasis‐directed therapy within the context of tumor‐related molecular factors and clinical variables like comorbidities is a separate issue that remains relatively less well answered. To better risk stratify patients who have oligometastatic disease and to determine optimal treatment strategies, future efforts should focus on conducting high‐quality, prospective trials and determining a biologic categorization of patients who have disease with limited metastatic potential.
That’s a mouthful Patrick. For me I think it says de novo oligometastatic may be a unique version (stage) of our Stg IV PCa that is possibly responsive to a different treatment path than other PCa cancers…..
When I started the second part of my PCa journey (the first being initial diagnosis, apalutamide trial, and surgery), I found that I had a tumor on my R clavicle with an Axumin scan and was started on Lupron and Abiraterone. The SABR-COMET trial results had just come out and based on those results, I chose to do SBRT to my oligometastatic lesion. I was told on another forum by one individual that this was a bad idea, that SABR COMET was a bad study, there was no benefit to SBRT, there was no abscopal effect, there is no such thing as oligometastatic state, etc... All I had to do was read a blog and I would know all the answers... Wisely, I had to decline that offer...
Do I believe in the oligometastatic state...?? Absolutely !!!... I think Dr Tran, who did the ORIOLE trial explained it best as a Venn diagram, with the intersection of nonmetastatic and metastatic being that area... According to the long term results of SABR COMET, the OS was greater for SBRT-study below:
Metastasis Directed Therapy (MDT) is here to stay and beneficial for those having an oligometastatic state. I believe there is the potential for a cure for oligometastatic patients... Cleveland Clinic is now doing the Metacure trial--see below: , and I would do the trial, but my MO says that I am essentially following that pathway...
Will the RAVENS trial using Xofigo with SBRT show a combination treatment can result in a cure or provide longer disease control? We will have to wait a bit longer to find out...
In the meantime, I am aware that a number of oligometastatic patients on this forum have used a combination of ADT plus ARPI drugs with SBRT to provide extended disease control (one member is almost 5 years out for vacation)...
With improved scans like Pylarify, tumors can be detected earlier and metastatic burden can be kept at a lower level... Logically, this should result in improved PFS and OS, but the data is not there yet... Despite the lack of data, MO's are beginning to use SBRT and shorter treatment times for oligometastatic patients (1 yr vs 2 years)...
We are in the infancy of treating the oligometastatic state, so whether you are a "de novo" or "oligo recurrent" patient, the future appears bright moving forward... because...
On some forums, you will hear some poster advocate never stopping treatment because your disease will get worse... Do continuous therapy !!! Posters that are not PCa patients advising continuous therapy have "no idea" what dealing with the side effects of treatment is like...day after day... ADT is no pleasure cruise !!!
The reality is that when evaluated in a number of trials, intermittent treatment was found to be "not inferior" to continuous therapy. More study is needed on this subject, but if you have a less aggressive disease, then taking a break makes sense for the bone, cardiac, and other benefits of a eugonadal testosterone level..
Each patient must determine their course with their MO, and should not listen to some poster on a forum... just my opinion...
Agree, Fish. And further complicated in that any treatment, if continued long enough, selects for resistant strains and assures it’s eventual failure. Continuous ADT leads inexorably to castrate resistance. Very difficult personal decisions. Pablo
When one is in the Stage IV, the PSA matters less than the disease involvement/ tumor involvement , genetic malformations, reaction to treatment, and aggressiveness of the disease. I have seen studies pointing to lower PSA having a survival advantage, but I believe that is being reviewed still.
Recently, on getting the results of my PET/CT I was going to get SBRT to the 4 spots found on the scan. My RO decided against it after further review of my CT done prior to the PET but said it is common with other cancers and my MO was on board from the get go. He said there is a PET/CT and a SBRT in the same machine where they find the met and radiate in the same session. I mentioned that in the forum and somebody said they were scheduled on it a few days later. So I agree it seems that is where we may be headed. The bottom line for me was my RO said for me it was a all or nothing deal and since one of the LNs would move from me breathing it would not get the right does and so the whole thing was off.
Sorry to hear it.. Location has to be factored in.... why irradiate if you will cause the demise of the patient??In the meantime, watch for trials that could help....
I agree and the dialog with my RO before his decision still has me a bit confused but I will ask him more questions next week, I am. I was hoping to get into a Pluvicto for hormone sensitive but prior Zytiga use disqualified me.
Thanks for posting. I agree with Fish above that we should not give up on the potential for cure in an oligometatastic context but equally in my case I am viewing the direct treatment of what can be seen (without ignoring what we currently can see) as being potentially helpful in the management of my cancer and in the difficult QOL/treatment trade offs. For sure we are going to learn more as we go along
I think it goes even further into Adaptive Theory... Sure QOL vs Treatment is important to us as patients, but then there is the concept that using adaptive theory to monitor treatment and reduce the risk of resistance. Here is one recent small study, but there are more studies indicating that continuous treatment may not be "the way to go..."
If this works well in MCRPC, then how much better will it work for MHSPC??? Prolonging the effectiveness of drugs in treatment buys us.... TIME !!! Time means new developments occur, new trials, new drugs, new treatment... and that buys us.... MORE TIME !!!
Do I think micrometastases exist??? Indeed, I do... but should our focus be on doing continuous treatment for metastases that we can not see that may be 0.2 mm or so, or should we focus on prolonging the utility of medications and QOL ?? I vote for the latter...
Will we see improved scans that can see micrometastases?? Maybe.. and will that lead to a cure as we can decrease the tumor burden further?? .. Again,,,maybe...In my opinion, getting the immune system to do more to annihilate PCa is the key..
Yes I had missed that as part of the benefit. The Adaptive Theory is very interesting and buying time is the name of the game for many of us. Thanks Dave and best wishes to you.
You are wright. Delaying more advanced system treatments with SBRT of visible mets could buy us time. And hope for new treatment in the future. Totally agree.
"Prolonging the effectiveness of drugs in treatment buys us.... TIME !!! Time means new developments occur, new trials, new drugs, new treatment... and that buys us.... MORE TIME !!!"
That is a very impressive small study of adaptive Abiraterone. Stopping promptly when PSA dropped by 50%, a very simple adaptive strategy, nearly doubled mean overall survival. Wonder what would have been result if they also stopped and cycled their ADT? (Best accomplished with Orgovyx oral ADT.)
Not impressed at all! They are, at least, 3-4 decades behind our time with their on/off scheme. Sometime in the (I hope) not too distant future, they will find out that by constantly adjusting up/down the dosage, far better/tighter control can be achieved compared to any fixed dosage start-stop switching. I am following this route in my N=1 adaptive Bicalutamide experiment with, up to now, very encouraging results. For the uninitiated, as many among you already know my doings, details are posted in this thread:
This was with MCRPC, so one wonders with MHSPC...It is a small study, but one of several confirming that continuous is NOT superior... If I could chose to be on meds only 1/2 or less of my life and have normal testosterone levels the rest of my time, then why wouldn't I??? Cycling ADT with Orgovyx... getting to normal faster... and slowing resistance by reducing exposure to the meds... Reduction in bone loss/ fracture potential, cardiac damage by using intermittent vs continuous... I wonder what percentage of those that get Stage IV PCa die from prostate cancer vs cardiac or fractures ?? Are the vast majority of us living with Pca vs. dying from it, and of course... QOL..
It makes me wonder if people preaching continuous look at the whole picture?? Do not get me wrong...those with aggressive disease have to do what they must.. but for others.... things to consider...
No matter which side you choose... These are exciting times for PCa patients... we have seen more progress in the last 10 years, than all the years before.. because...
Thanks for adding link to this article. It's very interesting and relevant...at least in our circumstances. One to be saved.
Going back to Patrick's initial post, I think you told me that as Ron's initial bone and lymph node metastases from PSMA (April 2019) were apparently 'resolved' (PSMA April 2021) apart from one at T3 he probably would be classified as oligoprogressive...at least I think that's what you wrote... not certain but know it was one of the 'oligos'. The met at T3, as you know, was growing at a speed of knots... SUV 6 to 58 in a matter of months and PSA x3 in a couple of weeks so MO added Abiraterone to Lupron (Sept 2021) and then SBRT.
Just a couple of things...
Although the earlier mets were 'resolved' according to the PSMA would that mean that there would still be micro cancer cells circulating but they don't show up in PSA?
In the article, the outcome for the control group sits pretty well with everything I've been told by our MO and read about what to expect with Abi. So it would seem fairly obvious that unless you're very lucky and one of the few, the outcome for most is eventually drug resistance. From others I communicate with, who do take ADT as a matter of course (including Abi and Enza) it does seem that exercise and a careful diet do seem to make some, not inconsiderable, difference to the outcome.
And yes definitely. It is about buying time.
Once again, invaluable input from you and the others in this post. Thank you.
Sorry about the delay in response, I am still playing "catch up" on FPC forum... Indeed, Ron was polymetastatic initially I believe, and post systemic treatment showed only one tumor but progressing significantly, thus similar to oligoprogressive...
As we discussed, I believe that SBRT to that resistant lesion could result in better disease control. At this point, there is more study needing done on oligoprogressive disease, but it sounds like Ron is doing well at this point. The real question is what scans are showing post treatment, and how his PSA is doing...
Yes, there are micrometastases, but the question is how many have been killed since his SBRT via the abscopal effect and the new regimen with abiraterone... As per my discussion with the Dog of Terror in another post, micrometastases are more about finding a hospitable location to grow and developing nutrients, blood supply, etc, so they do not produce PSA like a developed tumor...
Like a lot of things, time will tell... Keep things running smoothly at Peter Mac and in Oz... Are you running for PM next term?? Anthony Albanese is already worried...
You don't need to apologise. Your replies always insightful, well informed and worth waiting for.
Ron hasn't had any scans post SBRT treatment but PSA's been undetectable...guess he won't have another PSMA unless there's a change. A new PSA in a couple of weeks so we'll see how that goes. As you and I have discussed, Abi has given him a new lease on life after the 10 months on Enza which stripped away any QOL. These last eight months have been so different. It's only in recent weeks he's started to find things a bit of a struggle and run out of steam earlier in the day than has been the case in recent months. Not such a good week this week. Hoping it's just a minor hiccup... perhaps related to other conditions.
His gastroenterologist, who of his own volition, takes on the role of case manager organises a CT scans and extensive blood tests every six months. It was because of these that we discovered the kidney function problem late last year. He's very thorough and we'll see him just before we see the MO so if anything shows up in the bloods (which he usually says are 'pristine'...must be the red wine...) he'll pick it up.
Yep, Peter Mac work still going well. Unlike you, I've not been involved in a medical facility before as a component of my professional work. I never cease to be amazed at how rigorous they are at working towards optimal care for patients and making sure patients are at the centre of the decision making and most important being listened to and actually heard. As it's a dedicated cancer centre I think that makes a big difference. Their whole focus is on cancer treatment and care from diagnosis through all stages. Most impressive and it's easy to see why they are recognised as a world leader in some areas of cancer research.
Politics here have changed somewhat over the last eighteen months and both Nationally and in all States and Territories, except Tasmania, we have a Labor government in power. Pretty sure AA has nothing to fear from me...and certainly nothing to fear from the opposition either if they don't get their act together.
Keep posting and responding...yours is a unique voice and you always add interesting commentary and additional input to the post of others. Invaluable.
My husband had 'spot radiation' to a previous met that had lit up at an annual scan. It was a one time very high dose radiation 'hit' to the T4 spinous process where the met was located. We understood from the MO and RO that it wasn't a technique used often. But it seems to have worked.
Glad it worked out... I had a friend of mine do that for her husband... I call it "removing resistance" since that one lesion was a leftover after treatment... if it is treatment resistant, then annihilate it and remove the ability of that tumor to use mRNA to pass that ability on to other tumors...
Very good to see you back in the game, NP/DD. Also, a fine observed distinction re: "removing resistance". I'd never considered that as a possible reason for persistent mets and the strategic medical advantage of eliminating them. I often think patients see what docs sometimes miss. This might well fit into that category. Hope all is well with you and yours, Lady M, son, Bro', etc. Catch ya' later - Keep it S & W, Ciao - K9
When one considers the whole micrometastatic environment... tumors, then breaking off pieces of tumors, and circulating tumor cells, the issue is how does one slow down the metastatic process ?? If the systemic treatment kills off tumor cells and CTC's, then why are we not cured?? Answer-- Resistance.
My Theory:
Resistance develops from treatment exposure and the development of treatment resistant tumors and CTC's that can pass on that developmental information via mRNA. Micrometastases are smaller and their metabolic activity is focused on development--finding nutrients and a hospitable environment. The info for resistance comes from the larger tumor(s) via mRNA, but what if we eliminate the tumor(s)?? The source of information for resistance is removed or that information is reduced dramatically. Tumor burden and the information to develop resistance is reduced which should result in slower TTP just like in the EXTEND study.. With SBRT, add the abscopal effect which will continue to kill tumor cells via T cell activation. Once they develop a way to eliminate T cell exhaustion or prolong the immune response, then they will be close to a cure for OMHSPCa. A vaccine, an immunotherapy drug like below:
Will trials like SABR COMET 10 or the one below determine if there is a limit in the number of tumors that can be treated with SBRT and systemic therapy??
Nice weather locally in combo with lunchtime arrival of jdm3 & his birdwatching co-pilot = guarantee for "great weekend". Enjoy yours whatever you do! Ciao - K9
As an "oligo recurrent", my treatment has not changed from when I was "de novo" ... My MO was against SBRT for one lesion in 2019... he said, "I don't know if that is such a good idea". Now, it is SOC... The first time, I was on Lupron and Abi for 22 months... this time, I am on Eligard and Abi for 12 months hopefully..... There is no Phase III trial proving that concept, and yet... it is being done... My MO confirmed at my last visit what I suspected... MOs talk to one another... they compare notes... The paradigm is changing so fast, that they will not wait for a Phase III that takes 5 plus years to change the treatment paradigm...
In regards to the science, it is evolving so rapidly that waiting for a Phase III trial to confirm treatment change is becoming obsolete... Sure, the Phase III is essential for the medications, but for treatment.... another story...
Degarelix is fine... You were polymetastatic on the spine initially with no visible mets now,,,, What type of scan and did you do the same scan when doing follow up?? If so, and your PSA is undetectable, then that sounds like things are copacetic...
Interesting and thought provocative as usual! Thank you for posting!
Interesting as well, when I was persistent post RP my MO wasn't so enthusiastic about treating the "spots"... Systemic SOC is what was offered and performed, of course with my indulgence! Unfortunately it didn't work out.
Fast forward a few years, and I think probably due to the data available convincingly supporting the continual "debulking" of lesions when found (my term and opinion). Is beneficial in some ways... Anyways, this past year after becoming resistant and recurrent once again, we "spot" treated, or used "Whack-a-Mole" treated those locations (SBRT - 30gy in 15 applications to tissue) evident/avid (barely) in my imaging/scans!
Only time will tell... But certainly in a few months with follow up scans to try and "see" evidence of efficacy. I'll be sure to let ya know if interested how it goes
I'm wondering if my husband would be considered oligometastatic. He had his prostate removed in April of 2021 and had a 6 month Lupron shot at that time. He has been undetectable since then until now. On 3-31 his PSA was 6.3 and on 4-3 it was 7.1
On 4-7 he has a PET-CT PSMA which showed positive lymph nodes as follows and nothing else: Pelvic and abdominal lymph nodes: Several adjacent the right retrocrural tiny tracer avid lymph
nodes measuring up to 1 x 0.7 cm with max SUV of 6.2 seen on image 190.
Tracer avid left para-aortic lymph node measuring 1.3 x 0.6 cm with max SUV of 20.1 cm on image 213.
Additional tracer avid left para-aortic lymph node measuring 0.5 x 0.5 cm with max SUV of 10.6 seen
on image 230.
Head and Neck: Tiny tracer avid lymph node at the left supraclavicular region with max SUV of 2.9
seen on image 105.
We have not talked to the oncologist, but he has started him on a 30 day course of Casodex and he will get a 3 month Lupron shot on 4-21. He meets with the oncologist on 5-22.
I'm just wondering if it is possible that radiation to the affected lymph nodes may be an option if this is consider oligometastatic?
I don't know why, but this has taken us by surprise because he has done so well for the last couple of years. I am also surprised that he went from undetectable to 6.3 in a 4 month period.
Unfortunately that is just too many sites to approach with SBRT as with oligomets (3 or less usually, or perhaps 4). The favorable thing is that they are all lymph nodal. And he is presumably hormone sensitive. Adding an AART drug to the Lupron such as enzalutamide, darolutamide or abiraterone is proven beneficial. Chemotherapy with docetaxel should be discussed with his MO also.
Other advanced treatments such as Pluvicto and Provenge are not approved until he becomes castrate resistant. A “catch 22”. He could go abroad and self pay for Lu177-PSMA (Pluvicto and similar) while hormone sensitive, or look for clinical trials for mHSPC. Best wishes to you both. Paul
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