Decision: 2 or 3 Years on Lupron? (or longer?)

My doctor has given me a choice. I've been on Lupron for 2 years (1 shot every 3 months) and finished 44 radiation treatments (IMRT/IGRT) Dec. 2013;. The cancer was not confined to the prostate, but was considered localized (i.e. it had spread to the lymph nodes), so I was told the chance of a cure is between 20-40%. My PSA has remained undetectable since radiation finished. And I'm coping with the usual side-effects, so they don't play a significant role in my decision.

The doctor thinks it is fine to stop the shots now, but says I can continue getting Lupron shots, if I want them. He says there is not sufficient data to say whether 3 years is better than two. On the one hand (assuming the cancer will return), it feels like an extra year of shots will buy me an extra year of life. On the other hand, again assuming my cancer will return, it feels like resuming the shots after waiting until the PSA rises will delay the onset of castrate resistant prostate cancer (CR-PCa), so that could buy me another year of life, also. On the other hand (yeah, 3 hands), the fewer cancer cells there are, the fewer mutations, so staying on Lupron, will slow the chance of CR-PCa mutations.

I've told my doctor this, but he repeated that there isn't any data to help me make an informed decision, about which option gives a higher chance at a longer life. He says that if all I will do is worry about the cancer coming back, then maybe I'd be happier with another year on Lupron.

What should I do? Why not just stay on Lupron until CR-PCa develops?

ksargent ...

I'd encourage you to watch the High Risk Dr. Kwon video that Cicero and Hawaii posted this week. It talks about the need to take advantage of the situation when you get the PSA down and cancer on its heels. I don't think there are 'studies' to support this aggressive approach, because each case is different. But it sure makes sense to go after it before it's differentiated and / or resistant.

In my case, I'm planning to go off of the Lupron/Zytiga in a couple of months. My thinking is that we'll be able to see where any cancer is left, and kill it while it's still young. I don't think of it as a 'holiday', but as a 'feint' in my ongoing battle with the cancer. I'm withdrawing my troops (Lupron), but keeping my spies (monthly PSA test; C11 Choline scan when needed) -- if it comes back, i'll find it's new outpost ... and deal with it conclusively. Wash, rinse, repeat ...

Ray

You might want to make sure your PSA hits 0.01 before you consider stopping Lupron. Our oncologist for example, continues therapy until PSA is <0.01, and stays that way for a number of months.

There are enormous variations with different people, but your idea of keeping on therapy until you've wiped out as many PC cells as possible, is probably the most logical and safest approach.

If Lupron alone can't get you down to 0.01, then perhaps adding Casodex and/or Avodart will most likely do it. If Lupron gets you there, then there doesn't seem to be a reason to add anything else.

Arthur

Arthur

ksargent,

Your doctor is quite right. The optimal length of ADT for high risk men getting initial radiation is yet to be determined. What we know is that 28 months is better than 4 months, and it also may be true that 18 months is no better than 36 months.

You can read about the research on this so far here:
Androgen deprivation therapy and escalated dosing in radiation therapy

The reason why you don't want to stay on it longer than you have to is because the side effects of ADT treatment accumulate over time.

If your RT +ADT worked, it will have worked already, so there's no benefit to staying on ADT longer. If it didn't work (i.e., the cancer was not really local), there is also no known benefit to staying on ADT longer. In fact, in that case, it is an open question about the best time to re-start ADT. No one has seen a benefit to re-starting it earlier when there are no detectable mets, no symptoms, or PSA is not rapidly rising. And as you suggest, it may put more selective pressure on developing castrate resistance.

Your PSA<0.04 is excellent and means it's undetectable. It is no worse than Arthur's - it just means the labs report it differently. This is exactly what you'd expect being on Lupron. You will have to see how high it rises when you come off of it. Hopefully, it will stay under 2.0.

- Allen

What should I do? Why not just stay on Lupron until CR-PCa develops?

Is your doc an RO or a prostate oncologist? Given your age and that you are high risk, your should see a prostate oncologist such as Myers-Scholz-Kwon. They know systemic treatment better than ROs or surgeons.

Yes, Lupron can cause bone density issues in the long term, along with the other "problems".

Age 63
PSA 2.9 12/02, age 51
BX/DX, 9/03, G6, 4 of 12 cores
Brachytherapy 9/03
PSA nadir 1.1 5/08
PSA 1.8, 12/08
BX/DX, 2/09, G8, 1 of 12 cores
Hyperthermic, Hormone (one Lupron), IMRT (10) spring 2009
PSA nadir < 0.1 10/09 through 01/12
PSA 0.2 4/12
PSA 2.9 5/14
C11 Acetate PT/CT, found 2.0 cm lymph node 5/14
Lupron/Casodex 5/14
Nadir <0.01
2/15 SBRT to node
3/15 PSA 0.02,T=0
6/15 PSA<0.015,T=1

When combined with RT, HT masks whether the RT was effective or not...Your PSA drops to undetectable and everyone is happy...But to keep men on HT any longer than what provides a benefit is criminal the side effects are that bad...After 3 years of HT, a full recovery (from the effects of the HT) becomes difficult if not impossible...The effect becomes permanent...I stopped the HT at 24 months and enjoyed 6 months of zero club membership, thought I was home free....But no...9 months after I quit the HT my zero club membership was revoked and I was back on the lupron for the duration....

Lupron is nasty stuff. If the doc gives me the option of getting off early then I'm gone. Bye bye.

Tom

ksargent said...
With an undetectable PSA, my cancer has stopped growing, and there's not much in my body, if it's still there. If it's not growing, then there are no mutations that could evolve into castrate resistant PCa. Therefore, if I stay on it forever, I will live forever (sort of - at least I won't die of PCa). So, aren't the side effects worth a longer life?

Unfortunately, it doesn't work that way. The Lupron suppresses prostate cancer, but does not end it. If only it were true! Then we'd have a cure. The way it works in real life is PSA often goes to "undetectable" for some time, but then the remaining cancer evolves to become castrate resistant. There are always some cells in a tumor that are castrate resistant - they eventually come to predominate.

ksargent said...
Why should I take a chance, stopping lupron, just to see if I'm cured? If I'm not cured, that means the cancer will start growing and start mutating into castrate resistant PCa. Yes, I know, the therapy can be restarted, but the cancer cells now have a head start.

It's not "taking a chance" and you've got it backwards. Either you have been cured by the combined RT+ADT or you haven't. If you have been cured, there's no benefit to further Lupron, and harms accrue. If you have not been cured, there's absolutely no evidence that continuing to stay on it will enable you to live longer with it. In fact, it might even drive the cancer towards castrate resistance faster via a mechanism of selective evolutionary pressure.

- Allen

I was at a recent talk by Dr Lam about treating PC with HT and he said that data didn't show much difference between intermittent HT and continual HT in terms of cancer progression. (It may have even shown no difference...)

Of course, this is only relevant if you haven't been cured. As Allen points out, you may have been cured by the combined RT+ADT. Seems to me there's only one way to find out and that's stopping the Lupron.

BTW, I did 18 months of it and I sure feel better off than on it, but even after more than a year my testosterone has still not fully recovered.

Tall Allen said...
ksargent,

Your doctor is quite right. The optimal length of ADT for high risk men getting initial radiation is yet to be determined. What we know is that 28 months is better than 4 months, and it also may be true that 18 months is no better than 36 months.

You can read about the research on this so far here:
Androgen deprivation therapy and escalated dosing in radiation therapy

The reason why you don't want to stay on it longer than you have to is because the side effects of ADT treatment accumulate over time.

If your RT +ADT worked, it will have worked already, so there's no benefit to staying on ADT longer. If it didn't work (i.e., the cancer was not really local), there is also no known benefit to staying on ADT longer. In fact, in that case, it is an open question about the best time to re-start ADT. No one has seen a benefit to re-starting it earlier when there are no detectable mets, no symptoms, or PSA is not rapidly rising. And as you suggest, it may put more selective pressure on developing castrate resistance.

Your PSA<0.04 is excellent and means it's undetectable. It is no worse than Arthur's - it just means the labs report it differently. This is exactly what you'd expect being on Lupron. You will have to see how high it rises when you come off of it. Hopefully, it will stay under 2.0.

- Allen

This is so complex and frustrating.

What supports this statement "If your RT +ADT worked, it will have worked already, so there's no benefit to staying on ADT longer."? Isn't that kind of the whole question here? RT+ADT is better than RT alone, but how long does the ADT need to be continued?

The 2009 Bolla study (www.nejm.org/doi/full/10.1056/NEJMoa0810095#t=article)said 36 months is better than 6 months for high risk (T2c or higher cases) treated with EBRT (50 Gy pelvic, 70 Gy to prostate). The statistics specifically couldn't prove that 6 months was non-inferior to 36 months, so not "as good". That was with radiation techniques ancient by today's methods, though. So, one data point says 36 months is better than 6.

Dr. Nabid's ASCO presentation in 2013 (www.ascopost.com/issues/april-15,-2013/similar-outcomes-for-18-vs-36-months-of-androgen-blockade-in-high-risk-prostate-cancer-treated-with-radiation.aspx) said 18 months was as effective as 36, so maybe going more than 18 months is not of any further benefit. He didn't break out subgroup results I was looking for, e.g. "very high risk" cases like mine.

My MO is Dr. Maha Hussein at Univ. of Michigan. She isn't fully convinced about Nabid's study, and leans still on Bolla's since it's still the most solid available, albeit pretty old now. She thinks since this is my primary therapy we need to go for the full course of 3 years. I'm still not convinced, personally. Her point is she'd rather find 10 years from now that 3 years was too much, than find out 2 years was not enough. The data really don't exist yet to prove it, unfortunately. My radiation was much better than what they used in the Bolla study. That's what makes me very much inclined toward shorter ADT.

As usual Tall Allen makes good points, and it sure seems to me that if not 18 months then 2 years should be enough. How much incremental benefit at this point am I likely to get vs. the incremental risks from the accumulating side effects? Nobody can define the benefit with data, but the side effects are quite perceivable! I've been on ADT2 for 26 months now, due for another 4 month shot in July. I'm thinking I may refuse that one and just call it good at 28 months.

The side effects are hard to live with. I'm just not "me" anymore.