Rising PSA's after treatment - an answer

Oh early on in all my research I read about Orgovyx. It seemed like a no brainer except wasn't sure if insurance was going for it shortly after approved due to the cost? But because of all the benefits you mentioned, including pill instead of shot, it seems like you could make a compelling case to get approval.

I've heard horror stories on the low-T side effects - hot flashes, no strength/energy, muscle wasting, erectile dysfunction. On the other hand I heard other people made it a point to be in best shape possible before, do strength training and keep exercising, which sounded like it mitigated the side effects to an extent. Plus as you point out since the onset/offset is so rapid you therefore can rebound back to 'normal' from it more quickly.

That's an interesting decision point Oncologists have to grapple with. Let PSA go up to detect where the cancer is versus early pelvic radiation to try to prevent metastases in the first place.

I have the traditional Medicare and TRICARE For Life. The latter functions as Part D. A 90 day supply of Orgovyx has my co-pay at $68, so not an issue for me. I know for others with various insurance it is, both gaining approval and cost.

Side affects, the usual, hot flashes, mild fatigue, muscle and joint stiffness, genitalia shrinkage, some weight gain, about 8-9 pounds this go round. Bothersome, irksome, but not life altering. I still work which involves travel, most days I exercise, indoor bike, weights, swim. On weather cooperative days I ride my bike outdoors. For the last three years I have done the Garmin Unbound, a 50 mile gravel bike ride with my daughter or sister. Wife and I did two vacations this year, Iceland and Oregon. In January I went skiing in Colorado

It is an interesting decision point about when, with what and for how long when faced by clinical data such as a rising PSA only from an USPSA test. As with each of us, the decisions we make must be kept in context of our clinical history. My decision this time to wait until the PSA rose to .5-1.0 was based on my clinical history, surgery, SRT and triplet therapy. Were this a rising PSA after surgery in March 2014, I may very well not have waited and acted sooner, but...I would still have expanded the treatment zone to the PLNs, all of them, and added 6-18 months of ADT. In fact, at the time I chose SRT, I did act on two consecutive rising PSAs, .2 in September 2015 and .3 in December 2015 (there was no USPA at the time, or if there was, not mainstream clinical practice). Combined with my GS 8 and only 15 months to BCR, I knew SRT was the next step. There was no imaging at the time which would locate where the BCR was, my urologist and radiologist were welded to the SOC - SRT to the prostate bed. I had seen various data from CTs nd Mayo about the increasing evidence in guys like me, GS 8, short time to BCR, that PCa had spread to the PLNs and thus doublet therapy was warranted, extend the radiation treatment field gto the PLNs and include ADT for systemic therapy. I saw the data that said initiating SRT at lower PSA, some .3 or less, others .5, resulted in either "cures" or longer PFS. It makes sense.

Today we are faced with more or less the same dilemma for a rising PSA after surgery, treat at the first sign or, wait until PSA reaches a point that greatly improves the probability of imaging locating the recurrence, thus informing the treatment decision. The differences now and in December 2016, imaging, USPA, better software and hardware in radiology, ARIs....you get the idea, lots of differences!

So, a decision to do SRT as .05 is not "wrong." What may be "wrong" is not accounting for micro-metastatic disease and including systemic therapy and an expanded radiation treatment field other than just the prostate bed.

In my journey which is coming up on 10 years, my takeaway is to be proactive, have your specific clinical based criteria when deciding on when, with what and for how long.

In the four times I've treated, only wrong decision I've made is letting my urologist and radiologist talk me out of adding the PLNs and short term ADT to SRT. When we tested PSA 90 days after completing SRT and it had climbed to .7, they both apologized. The lesson learned was not wasted, never again would I passively let my medical team make the SOC my treatment and they became more active listeners to their patient.

I went to see the DIrector of Urology at a NCCN Center after that to discuss imaging with C11 Choline, then informed by that the use of triplet therapy, ADT, Docetaxel and radiation. He dismissed the idea, said he would out me on monotherapy, ADT for life...yep, I left, never went back, went to Mayo, had the C11 Choline scan done, did the triplet therapy and had 4-1/2 years off treatment. I have the same radiologist and brough a new oncologist on board, they both support my treatment decision this time, SBRT to the PLN identified in the Platify scan, 12 months of Orgovyx, then stop and monitor.

Kevin
Kevin

There's some more recent studies that show going before 0.2 has statistically better outcomes. Strangely one report cites an average SRT PSA of 0.08? Huh? Did these guys pay out of pocket or was this that low because they were doing ADT just prior? (I don't have the time right now to go over the report with a fine tooth comb I'll see if I can find the URL.)

I think it's safe to say doing SRT before 0.1 would be "aggressive" and "problematic" with the insurance company is my guess. Edit: Scratch that statement. Getting confirmation from multiple people SRT at < 0.1 should not be a problem with insurance. Looking at some graphs of studies showing PSA progression in cases of BCR after RP, if one is undetectable < = 0.03 the first year, although of course it varies between individuals, getting to 0.1 let alone 0.2 is very very unlikely going to happen in a year. Even at very short 4-month doubling time, for one year. a 0.02 would only end up at 0.08 after a year. So suffice to say, I've got a long time to think about things even if it comes to that.

I have the traditional Medicare and TRICARE For Life. The latter functions as Part D. A 90 day supply of Orgovyx has my co-pay at $68, so not an issue for me. I know for others with various insurance it is, both gaining approval and cost.

Side affects, the usual, hot flashes, mild fatigue, muscle and joint stiffness, genitalia shrinkage, some weight gain, about 8-9 pounds this go round. Bothersome, irksome, but not life altering. I still work which involves travel, most days I exercise, indoor bike, weights, swim. On weather cooperative days I ride my bike outdoors. For the last three years I have done the Garmin Unbound, a 50 mile gravel bike ride with my daughter or sister. Wife and I did two vacations this year, Iceland and Oregon. In January I went skiing in Colorado

It is an interesting decision point about when, with what and for how long when faced by clinical data such as a rising PSA only from an USPSA test. As with each of us, the decisions we make must be kept in context of our clinical history. My decision this time to wait until the PSA rose to .5-1.0 was based on my clinical history, surgery, SRT and triplet therapy. Were this a rising PSA after surgery in March 2014, I may very well not have waited and acted sooner, but...I would still have expanded the treatment zone to the PLNs, all of them, and added 6-18 months of ADT. In fact, at the time I chose SRT, I did act on two consecutive rising PSAs, .2 in September 2015 and .3 in December 2015 (there was no USPA at the time, or if there was, not mainstream clinical practice). Combined with my GS 8 and only 15 months to BCR, I knew SRT was the next step. There was no imaging at the time which would locate where the BCR was, my urologist and radiologist were welded to the SOC - SRT to the prostate bed. I had seen various data from CTs nd Mayo about the increasing evidence in guys like me, GS 8, short time to BCR, that PCa had spread to the PLNs and thus doublet therapy was warranted, extend the radiation treatment field gto the PLNs and include ADT for systemic therapy. I saw the data that said initiating SRT at lower PSA, some .3 or less, others .5, resulted in either "cures" or longer PFS. It makes sense.

Today we are faced with more or less the same dilemma for a rising PSA after surgery, treat at the first sign or, wait until PSA reaches a point that greatly improves the probability of imaging locating the recurrence, thus informing the treatment decision. The differences now and in December 2016, imaging, USPA, better software and hardware in radiology, ARIs....you get the idea, lots of differences!

So, a decision to do SRT as .05 is not "wrong." What may be "wrong" is not accounting for micro-metastatic disease and including systemic therapy and an expanded radiation treatment field other than just the prostate bed.

In my journey which is coming up on 10 years, my takeaway is to be proactive, have your specific clinical based criteria when deciding on when, with what and for how long.

In the four times I've treated, only wrong decision I've made is letting my urologist and radiologist talk me out of adding the PLNs and short term ADT to SRT. When we tested PSA 90 days after completing SRT and it had climbed to .7, they both apologized. The lesson learned was not wasted, never again would I passively let my medical team make the SOC my treatment and they became more active listeners to their patient.

I went to see the DIrector of Urology at a NCCN Center after that to discuss imaging with C11 Choline, then informed by that the use of triplet therapy, ADT, Docetaxel and radiation. He dismissed the idea, said he would out me on monotherapy, ADT for life...yep, I left, never went back, went to Mayo, had the C11 Choline scan done, did the triplet therapy and had 4-1/2 years off treatment. I have the same radiologist and brough a new oncologist on board, they both support my treatment decision this time, SBRT to the PLN identified in the Platify scan, 12 months of Orgovyx, then stop and monitor.

Kevin
Kevin

I find this discussion very relevant.
My most recent PSA was 0.08 on 1/5/2024. It was at 0.02 four weeks earlier 12/11/2023.
It was < 0.01 on 8/28/2023 when I just finished a 6 month clinical trial using Orgovyx and Erleada (with five rounds of radiation to a metastasis to a lymph node in my chest half way thru).
RRP was 3/25/2021. PSA 11.6
Post surgery lowest PSA was 0.37.
On 9/9/2021 PSA was 0.69 stared 34 rounds of Salvage radiation 9/27/2021.
On 12/10/2021 PSA was up to 1.29.
I was on active surveillance for the next 12 months until PET/CT found the metastatic lymph node in my chest. That is when I got into the METACURE trial.
My oncologist said that at 0.08 nothing would show up on a scan. My next PET/CT is in 8 weeks. So it looks like more treatments or trails are on the horizon for me...

Yes, one thing is for sure, you need do your own homework and analysis and not just rely on what the "experts' think. It's sort of a team effort and you are the leader of the team, not your Oncologist or Radiologist. They are just team members (with valuable input.)

If I have to do SRT, including the Pelvic area is a tough call given that I was Gleason 3+4 with PSA < 0.02 up to 16 month after surgery and no adverse post-RP pathology (clean margins, 14 negtive lymph node removed, etc.) BUT, and that's a big BUT, there seems to be an emerging trend in treatment that your chances of a cure, especially at your secondary treatment, is to essentially hit it with everything you got as early as possible.

If the go hard and early is the ticket, that would mean SRT including the pelvic area at PSA between 0.03 and 0.1 (SBRT is showing it is just as effective with only 5 treatments instead of the traditional 30 lower dose treatments), with ADT (6 months), and followup chemotherapy.

The other side of the coin reads "overtreatment/side effects with no benefit" Which translates to higher chance of Grade 3 side effects on the RT if you include the pelvic area, some unpleasant side effects from the ADT, and even more unpleasant I imagine from chemo. But the theory is, your best chance of eradicating the cancer is BEFORE it spreads and when micrometastases are at a minimum. It seems this common thinking that, "it's early" lets just start with "this" and then if it gets to the point we can see something on a scan we'll do "this also." By the time you can see something on a scan outside the prostate/prostate bed, I suspect the chances of a cure pretty low. You're just trying to slow it down.

So "on paper" (assuming you have support from your MO and Radiologist and no battle with insurance), it seems like it should be an easy decision to throw the kitchen sink at it as early as possible. Feel a lot crappier for longer in the short term, but with a higher chance of being cancer free in the long term. At age 55 am I going to completely lose erective function from SRT, no. Is ADT going to make my penis fall off? No. In fact my girlfriend would probably enjoy seeing me on ADT so I can experience what she's been going through with menopause the last 4 years. Will Chemo kill me at this age with this stage of cancer? No. Will all this stuff boil down to accelerating my aging for a while, probably.

So does it boild down to there's just not enough trial data on what I would term "early aggressive" treatment protocols to justify insurance paying for it all that early? (I'm guessing insurance won't pay for Doxatel if you have no tumors on your PSMA PET scan??? ) I'm sure of course there's also just not wanting to deal with bad side effects unless you're sure you need the treatment. Not a lot of people want to volunteer for chemo with a 0.1 PSA and their oncologist says they have no confirmation of metastatic disease?

I believe within the next 10 years, the medical technology will either have a cure or like HIV will be able to indefinitely keep the cancer at bay for the rest of your life which is already the case for man of those diagnosed within 10 or 15+ years or so of their life expectancy.

Yes, one thing is for sure, you need do your own homework and analysis and not just rely on what the "experts' think. It's sort of a team effort and you are the leader of the team, not your Oncologist or Radiologist. They are just team members (with valuable input.)

If I have to do SRT, including the Pelvic area is a tough call given that I was Gleason 3+4 with PSA < 0.02 up to 16 month after surgery and no adverse post-RP pathology (clean margins, 14 negtive lymph node removed, etc.) BUT, and that's a big BUT, there seems to be an emerging trend in treatment that your chances of a cure, especially at your secondary treatment, is to essentially hit it with everything you got as early as possible.

If the go hard and early is the ticket, that would mean SRT including the pelvic area at PSA between 0.03 and 0.1 (SBRT is showing it is just as effective with only 5 treatments instead of the traditional 30 lower dose treatments), with ADT (6 months), and followup chemotherapy.

The other side of the coin reads "overtreatment/side effects with no benefit" Which translates to higher chance of Grade 3 side effects on the RT if you include the pelvic area, some unpleasant side effects from the ADT, and even more unpleasant I imagine from chemo. But the theory is, your best chance of eradicating the cancer is BEFORE it spreads and when micrometastases are at a minimum. It seems this common thinking that, "it's early" lets just start with "this" and then if it gets to the point we can see something on a scan we'll do "this also." By the time you can see something on a scan outside the prostate/prostate bed, I suspect the chances of a cure pretty low. You're just trying to slow it down.

So "on paper" (assuming you have support from your MO and Radiologist and no battle with insurance), it seems like it should be an easy decision to throw the kitchen sink at it as early as possible. Feel a lot crappier for longer in the short term, but with a higher chance of being cancer free in the long term. At age 55 am I going to completely lose erective function from SRT, no. Is ADT going to make my penis fall off? No. In fact my girlfriend would probably enjoy seeing me on ADT so I can experience what she's been going through with menopause the last 4 years. Will Chemo kill me at this age with this stage of cancer? No. Will all this stuff boil down to accelerating my aging for a while, probably.

So does it boild down to there's just not enough trial data on what I would term "early aggressive" treatment protocols to justify insurance paying for it all that early? (I'm guessing insurance won't pay for Doxatel if you have no tumors on your PSMA PET scan??? ) I'm sure of course there's also just not wanting to deal with bad side effects unless you're sure you need the treatment. Not a lot of people want to volunteer for chemo with a 0.1 PSA and their oncologist says they have no confirmation of metastatic disease?

I believe within the next 10 years, the medical technology will either have a cure or like HIV will be able to indefinitely keep the cancer at bay for the rest of your life which is already the case for man of those diagnosed within 10 or 15+ years or so of their life expectancy.

I see your perspective, but I would like to suggest some other possibilities. My experience has been that cancer doctors are among the most optimistic MDs around and research cancer doctors are among the most optimistic cancer doctors. Therefore, I treat the new reports of "breakthrough" possibilities as just that, and the clinical standards of care as more sober realities. [They also get paid for treating, not for waiting :-), and for addressing their clients concerns and fears, even if they're not entirely rational.]
I think you're right that the "right time" to do salvage treatments after RP is drifting down. My urologist says around 0.10 (using ultrasensitive PSA assays) is probably the best guess. In my assessment his judgment is sober and well-informed.
The arguments about when to treat include health-related quality of life as well as longevity. Having just watched my sister die of a different cancer, I can testify that quality of life can vary a lot along the journey with cancer. These are hard issues to think about, much less know how we will feel when the time actually comes.
So I would say the "best hopes" will usually get scaled back and knowing that should also be taken into account when deciding on courses of treatment. For instance, I like to remind people that no one once diagnosed is ever "cancer free," that's just a convenient euphemism for "we can't find further evidence of your cancer at the moment with our current diagnostic tools." Instead, once my cancer reaches a certain stage (mine is stage 2, I believe) I will never be reversed to stage 1, much less stage 0. To be crass, I have a bell in the garage and I can ring it whenever I want. When I "ring the bell," I'm just hoping I won't have to come back again for a good while. But sometimes that's because there is no longer any effective treatment available today--in 10 years, maybe, but I was alive 30 years ago and the hope was exactly the same. And yes, we do have better treatment strategies and techniques and longer lives with higher hrQOL, but also yes, people are still dying from prostate cancer.

Here's some "light" reading... " https://www.urotoday.com/library-resources/mhspc/147798-the-current-state-of-treatment-implementation-for-mhspc-in-north-america.html?utm_source=newsletter_12452&utm_medium=email&utm_campaign=the-underutilization-of-treatments-and-testing-in-advanced-prostate-cancer

For those who don't want to wade through he charts and data...

Conclusions:

Although there appears to be increasing utilization of treatment intensification in the real-world setting, less than half of mHSPC patients receive guideline concordant care. While there may be altruistic reasons to avoid treatment intensification secondary to concerns for patient financial toxicity or concerns for the tolerability of these agents, the proven survival benefit conferred by this treatment paradigm should make this approach the clear standard of care. Based on the current evidence, it appears that patients with synchronous, high volume mHSPC benefit from early treatment intensification with triplet therapy in the form of both an ARPI and docetaxel, whereas the remaining mHSPC subgroups benefit most from doublet therapy with ARPI addition to ADT. Radiotherapy to the prostate is also associated with improved overall survival in mHSPC patients with synchronous, low-volume disease and should be considered in these cases.

Here's some "light" reading... " https://www.urotoday.com/library-resources/mhspc/147798-the-current-state-of-treatment-implementation-for-mhspc-in-north-america.html?utm_source=newsletter_12452&utm_medium=email&utm_campaign=the-underutilization-of-treatments-and-testing-in-advanced-prostate-cancer

For those who don't want to wade through he charts and data...

Conclusions:

Although there appears to be increasing utilization of treatment intensification in the real-world setting, less than half of mHSPC patients receive guideline concordant care. While there may be altruistic reasons to avoid treatment intensification secondary to concerns for patient financial toxicity or concerns for the tolerability of these agents, the proven survival benefit conferred by this treatment paradigm should make this approach the clear standard of care. Based on the current evidence, it appears that patients with synchronous, high volume mHSPC benefit from early treatment intensification with triplet therapy in the form of both an ARPI and docetaxel, whereas the remaining mHSPC subgroups benefit most from doublet therapy with ARPI addition to ADT. Radiotherapy to the prostate is also associated with improved overall survival in mHSPC patients with synchronous, low-volume disease and should be considered in these cases.