How long will Lupron work before prostate cancer becomes resistant?

Posted by bruningk @bruningk, Apr 30 7:19am

After radiation my PC is considered incurable and I’m on Lupron for the rest of my life. I realize it will become less effective over time and just want some ideas about how long will the Lupron work. It is able to send my PSA back to .05. I get an injection in the belly every 3 months and after the third injection, Oncologist gave me a short break off the treatment. After three months off psa still .05. After six months off still .05. I just checked again after 9 months off and I’m now .39, a substantial increase from three months prior. I’m back on the Lupron and hoping it sends me back to where I was before the break. I guess since my Oncologist is hesitant to give any timing on all this, I would like to know how long before I have to add some other type of treatment to extend my life. No metastasis yet thankfully.

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

We are on new ground here. ADT with the ARSI's along with triplet therapy are new. The doctors really do not know how to estimate OS because those of us on triplet therapy are the new active metrics.

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@russ777

I understand your anxiety bruningk and empathize with you. Unless I missed it I didn't see anything about your staging. Where was the cancer located when you were scanned prior to going on ADT? I presume not confined to prostate? And what was the radiation field?

I've tried to understand the answer to this question and have come across several interesting facts, anecdotal evidence and opinions. Most of this is from memory from things I've read in studies or seen/heard oncos say at conferences or in youtube vids.

1. Disease burden matters. The more extensive the mets, the more mutated the cancer cells and less like the "mothership" they become. Thus they become less susceptible to drugs designed to starve cancer cells of the fuel, DHT or testosterone. I've spoken with guys who've had mets and have been battling PCa for many years, 25+ in one case. I think they had a relatively low, though advanced, disease burden when diagnosed.

2. PSA doubling time is a strong predictor of eventual metastasis and the subsequent transition to CRPC 2-3 years later (though you can become CR without metastatic disease). There is a point of inflection in the curve showing probability of developing distant mets versus PSADT. That occurs around a PSADT of 7 months and increases as PSA decreases further. My PSADT when my PSA took off after RP was around 8 months, so it was aggressive but possibly controllable over the long term. You should ask your onco what your calculated PSADT is based upon it shooting up from 0.05 to .39. There may be some nuances in the calculation I'm not aware of but on the surface it appears you have a pretty short PSADT. Of course this particular graph is probably not directly applicable to your question, but its a morsel of data.

3. Dr Mark Scholz made a very puzzling statement on one of his videos a couple of months ago regarding how long ADT treatments work. He didn't explain the exact context, but his comment was that these days with newer treatments the time to CR has been estimated to be around 17 years. I rewound the tape and relistened to it several times, but that was basically what he said. I'm not even sure how that is possible when the latest ARSIs have only been on the market about 5-7 years, though it is certainly possible to estimate parameters like that given data collected over a shorter period of time. I even called their (PCRI) support staff and asked about it but they had no answer.

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Thank you for the info but my head is spinning! That’s a lot to absorb but shows I’m not up to speed on my situation. I think if I understand my situation, no Mets yet. They mentioned lymph nodes but bones seemed clear. So if I understand you, my cancer doesn’t become CR until it spreads? Not while it’s contained in the prostate?

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@russ777

I understand your anxiety bruningk and empathize with you. Unless I missed it I didn't see anything about your staging. Where was the cancer located when you were scanned prior to going on ADT? I presume not confined to prostate? And what was the radiation field?

I've tried to understand the answer to this question and have come across several interesting facts, anecdotal evidence and opinions. Most of this is from memory from things I've read in studies or seen/heard oncos say at conferences or in youtube vids.

1. Disease burden matters. The more extensive the mets, the more mutated the cancer cells and less like the "mothership" they become. Thus they become less susceptible to drugs designed to starve cancer cells of the fuel, DHT or testosterone. I've spoken with guys who've had mets and have been battling PCa for many years, 25+ in one case. I think they had a relatively low, though advanced, disease burden when diagnosed.

2. PSA doubling time is a strong predictor of eventual metastasis and the subsequent transition to CRPC 2-3 years later (though you can become CR without metastatic disease). There is a point of inflection in the curve showing probability of developing distant mets versus PSADT. That occurs around a PSADT of 7 months and increases as PSA decreases further. My PSADT when my PSA took off after RP was around 8 months, so it was aggressive but possibly controllable over the long term. You should ask your onco what your calculated PSADT is based upon it shooting up from 0.05 to .39. There may be some nuances in the calculation I'm not aware of but on the surface it appears you have a pretty short PSADT. Of course this particular graph is probably not directly applicable to your question, but its a morsel of data.

3. Dr Mark Scholz made a very puzzling statement on one of his videos a couple of months ago regarding how long ADT treatments work. He didn't explain the exact context, but his comment was that these days with newer treatments the time to CR has been estimated to be around 17 years. I rewound the tape and relistened to it several times, but that was basically what he said. I'm not even sure how that is possible when the latest ARSIs have only been on the market about 5-7 years, though it is certainly possible to estimate parameters like that given data collected over a shorter period of time. I even called their (PCRI) support staff and asked about it but they had no answer.

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«Dr Mark Scholz made a very puzzling statement on one of his videos a couple of months ago regarding how long ADT treatments work. He didn't explain the exact context, but his comment was that these days with newer treatments the time to CR has been estimated to be around 17 years.»

They must be trying to fit a bell curve to their early results (e.g. 6 years since FDA approval for Apalutamide, plus some info from pre-approval studies). Anyone who works with data knows that that curve-fitting is only slightly more accurate than asking a Magic 8-ball, but still, the observations and instincts of the top PC oncologists seem to be telling them they''re in the middle of a seismic shift — they're trying to sound cautious with us because you can never be sure about a major change like that until it's already in the past, but they're not great at hiding their new optimism.

As I mentioned elsewhere, the head of my onco team revised my possible time to castrate resistance to 10+ years, from just 1½ to 2-ish years when I was first diagnosed.

Grab an overhead strap and hold on tight, because the treatment train for stage-4 PC is moving forward crazy fast, wherever it ends up taking us.

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@wooldridgec

We are on new ground here. ADT with the ARSI's along with triplet therapy are new. The doctors really do not know how to estimate OS because those of us on triplet therapy are the new active metrics.

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Ok you mentioned two words I’m not familiar with. What is ARSI and triplet therapy. I understand ADT but I’m in Lupron and know nothing about what you mentioned. Thank you though!

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@bruningk

Thank you for the info but my head is spinning! That’s a lot to absorb but shows I’m not up to speed on my situation. I think if I understand my situation, no Mets yet. They mentioned lymph nodes but bones seemed clear. So if I understand you, my cancer doesn’t become CR until it spreads? Not while it’s contained in the prostate?

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The way my onco team explained it to me, prostate-cancer cells need testosterone to spread, but eventually they mutate and produce their own — that's when they become castrate-resistant. Androgen-reception inhibitors like Apalutamide (Erleada) slow that process down a lot (we're not sure just how much yet, but it seems to be by many years).

Since I was already stage 4 we didn't talk about earlier stages, but from other things I've read I think that applies in general (assuming you're not able to eliminate a localised cancer completely via a prostatectomy, radiation, etc).

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The "triplet therapy" is hitting advanced prostate cancer with three different attacks up front (e.g. radiation, ADT, and chemo). I think it's less common with castrate-sensitive, oligometastatic PC than it is with castrate-resistant and/or widely metastatic PC, but I am neither a medical professional nor a research scientist, so please verify with your own onco team.

ARSI (androgen-reception signal inhibitors) like Zytiga, Erleada, and Xtandi complement ADT (androgen-deprivation therapy) — the ASRI prevent the cancer cells from receiving the testosterone signal (even, to a certain extent, if once the cells have become castrate-resistant). I think it's becoming standard to prescribe both for advanced prostate cancer these days rather than just ADT alone, especially after the significant improvement demonstrated by big studies like TITAN, but they're also expensive (thousands of $$/month) if you don't have your government, private insurance, or a patient-access programme covering them.

https://www.nejm.org/doi/full/10.1056/NEJMoa1903307
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@bruningk

Thank you for the info but my head is spinning! That’s a lot to absorb but shows I’m not up to speed on my situation. I think if I understand my situation, no Mets yet. They mentioned lymph nodes but bones seemed clear. So if I understand you, my cancer doesn’t become CR until it spreads? Not while it’s contained in the prostate?

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Sorry, didn't mean to overwhelm you!

So if you have a few pelvic lymph nodes that were tracer-avid (i.e., took up the PSMA tracer agent on the scan) but no visible mets out of the pelvic region in bones or organs, you have locally advanced staging. Technically it's Stage 4a, but is not Stage 4b which means distant mets.

I suspect what your onco meant was that some if not most consider the disease "incurable" once it escapes the prostate. Radiation to the pelvic areas showing cancer presence and areas in the pelvis that do not show disease but where it could be present at the cellular or micro-met level can be curative. But being declared "cured" means no detectable disease for a period of 10 years. That's a tough criterion to reach.

But as has been discussed here, because of these 2nd generation drugs the battlefield is being reshaped, so to speak. Dr Mark Scholz is one of the prominent oncologists who believes the disease can be cured these days as long as it is oligometastatic (less than 5 distant mets) or confined to the pelvis.

I am unsure what to make of the idea that you're incurable because radiation failed to kill all the cancer. I'd engage your onco and get him to explain things better.

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@northoftheborder

The "triplet therapy" is hitting advanced prostate cancer with three different attacks up front (e.g. radiation, ADT, and chemo). I think it's less common with castrate-sensitive, oligometastatic PC than it is with castrate-resistant and/or widely metastatic PC, but I am neither a medical professional nor a research scientist, so please verify with your own onco team.

ARSI (androgen-reception signal inhibitors) like Zytiga, Erleada, and Xtandi complement ADT (androgen-deprivation therapy) — the ASRI prevent the cancer cells from receiving the testosterone signal (even, to a certain extent, if once the cells have become castrate-resistant). I think it's becoming standard to prescribe both for advanced prostate cancer these days rather than just ADT alone, especially after the significant improvement demonstrated by big studies like TITAN, but they're also expensive (thousands of $$/month) if you don't have your government, private insurance, or a patient-access programme covering them.

https://www.nejm.org/doi/full/10.1056/NEJMoa1903307

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Should mention that abiraterone is available as a generic now at a cost much less than the newer ARSIs. It has a fundamentally different method of action. It's a 2nd generation anti-androgen that interferes in the production of testosterone and DHT wherever in the body they're produced - testes, adrenal glands and PCa cells that have gone rogue trying to create their own adrenal glands.

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@bruningk

Thank you all for the great info. One last question, my doc said incurable now since radiation failed. Do you all agree with that and things like salvage prostectomy, cryoblation, and Brachytherapy are off the table?

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Dont hit your panic button. Listen very carefully to your doctor. Not curable does not equal terminal. OK?
Best go back to your doctor for recommendations of treatment. If not satisfied, go to another doctor. All we can do is share our experiences. That is very limited. The doctors have much wider experience. Some have thousands over decades.
Dont mind me. I am just another layman, and getting long winded.

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@northoftheborder

Is "Johns" Johns Hopkins Medicine? I'd love to read more from that source if you have the link.

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See if I can find it. I just keyed what is undetectable or what is cure something like that.

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