Should long-term ADT be added to RT for high risk PC?

Yes! (this applies to initial treatment only - not salvage. For intermediate risk, probably not)

Finally we have a randomized clinical trial (DART 01/05) of high dose EBRT (3DCRT) comparing Long Term ADT (LT=28 mos. total) to Short Term ADT (ST=2 mos neoadjuvant+ 2 mos. concurrent). We have known there was a benefit when lower doses (70 Gy) were given, but there was a question about whether it was still needed with higher doses (median 78 Gy).

For the high risk patients, there was statistically significant improvement by adding long term ADT:

• 5-yr biochemical disease-free survival: 88% LT vs 76% ST
• 5-yr met-free survival: 94% LT vs 79% ST
• PC-specific mortality: 0% LT vs 3% ST (up to 9 yrs f/u)
• 5-yr Overall Survival:96% LT vs 82% ST

• acute Grade 2+ rectal and urinary toxicity were not different for LT vs ST
• late Grade 2+ rectal and urinary toxicity were not different for LT vs ST. Same for late Grade 3

So if a patient is high risk, the addition of long-term ADT to high dose radiation improves all outcomes without incurring extra rectal and urinary toxicity as compared to a short course of ADT.

This does not answer:

• How does high dose RT ± ADT (LT and ST) affect erectile function? (I think this was collected but not yet shown)
• What is the effect on urinary, rectal and sexual function of LT ADT vs no ADT?
• Are there subgroups (e.g., age, comorbidity) for whom ADT confers no benefit?
• Is 18 mos. of ADT just as good as 28 mos.?
• Does RT+LT ADT give better/same/worse outcomes vs brachy boost therapy or SBRT without ADT?
• Does adding ADT (LT or ST) improve outcomes in high risk patients receiving SBRT or or brachy boost therapy? And how does SBRT or brachy boost±ADT affect urinary and rectal toxicity?

Post Edited (Tall Allen) : 9/25/2014 1:55:21 AM (GMT-6)

Thanks Tall Allen.

I think the first couple of those unanswered LT questions are automatic given Lupron's aility to totally destroy libido.

Irrespective of RT or SBRT or brachy I thought there was a conclusion recently that for high risk continuous ADT was better than intermittent.

LupronJim

Allen,

Any data on ADT with adj radiation? Meaning surgery followed by radiation with and without HT.


Jim - for those that need HT (aside from this study) yes, studies show continuous is better than Intermittant. Also that chemo+ adt out of the gate is superior. Both, however, are a tough sell to guys who probably prefer to be off HT and try to avoid chemo. I think Allen's point though is that you are going for the curative approach and hopefully won't need either at some point. If I understand that correctly...Awesome...

Jerry

Allen

Thanks for the information. This is exactly my situation. My RO wants me to stay on the ADT for the full 28 months. My Med. Onc says 6 mo or so is probably enough. I go see my RO on Monday and he was at the ASTRO meeting. I imagine we will have another discussion about this. I am not having much problem with the ADT except for the doable hot flashes. They are a small bother. Hopefully this treatment will get me another 10 or so years without having to mess with it. Guess I will go the full long term.

Carl

I appreciate seeing this study...it doesn't quite capture my situation as I had HDR brachy and IMRT with my ADT. That said, it seems logical that there would be similarities in outcome. That said, I did the shorter 18 months of ADT...Dr Lam felt that was appropriate given the additional use of Zytiga as part of my treatment. (Fingers crossed.)

BTW, I had posted this on the G9 thread a few days ago, but five months after finishing my HT, my testosterone is up to 179 and my PSA is 0.08.

I am not sure I agree with the study’s chosen end point. Shouldn’t the end point be different for the two treatment groups? ADT has been shown to be effective, at least for a while, in most men. Assume radiation fails to be curative in a subset of the men. Adding ADT to this group will delay biochemical reoccurrence but it will not necessarily be curative. It seems this might account for the 10% difference. If the group with 24 extra months of ADT were measured 24 months later than the other group, and there was still as statistically significant difference, this would be impressive.

There is some new insight also into my question of whether ADT benefits high risk men who are treated with a brachy boost. It was only a small study from Moffitt, and needs to be validated in a larger randomized clinical trial. They gave 28 vs 0 mos. of ADT for high risk, and 4 mos. vs 0 mos. of ADT for intermediate risk. Median f/u was 5 years (and up to 12.8 yrs).

They found "There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. "

It may be that brachy boost therapy reaches the upper limit for cancer control and adding extra ADT contributes nothing more. There are larger studies in the works to confirm this.

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer.

This is my situation-high risk. I had 36 months of HT at my urologist's urging. My med onc said a minimum of 18 months was needed. Both agreed on HDR Brachytherapy and IMRT. Their HT suggestion was based on the best information at that time (2010) the BOLLA Study from SWOG.

In choosing treatment I favored my uro as he has had a lot of experience with high risk and says in his experience the actual severity is most often worse than the clinical and biopsy findings show. My med onc who also has worked with a lot of high risk cases agreed, but at that time was favoring intermittent HT. Neither wanted me on Casodex long term, just Lupron/Eligard and Jalyn. Both continue to want me to stay on Jalyn for maintenance.

Tall Allen's information bolsters my confidence in the treatment decisions we made. As my HT side effects diminished the longer I was on, I am not so sure there would have been a meaningful difference between 28 and 36 months in my case.

Allen,
I have no idea how this would apply to me except for a small one that it doesn't. I was just looking at the long term ADT being defined as 28 months while I've been on ADT for 88 months and counting. At Dx I had 2 small bony mets that were shrunk by ADT and after all this time and 5 CT and bone scans nothing has shown up. My MO has me signed up for a govt. Clinical trial whenever the mets do show and it consists of more hormones, no radiation or chemo. No complaints it's just that I can't find a single case on this board that matches my own so I have no idea where I'm headed . . . Qp

Yeah you're right as usual Allen. The G9s are still lacking in a case similar to mine though. I guess I'd better do a search for mCRPC and see what turns up . . . Q

PS: No luck with the search function, just got threads for a different alphabet soup disease. I'll continue down the thread.

Post Edited (quincy17) : 9/27/2014 3:21:05 PM (GMT-6)

Allen,

Thanks. No, I didn't ask for an ultrasensitive PSA, the URO and MO did. Guess I thought that was the truest one?

I mentioned Avodart because Dr. Myers says it is the DHT not T that tells PC cells to grow or not so it should be kept below 5.0. He an Dr. Scholz stress maintaining a durable remission with Avodart or Proscar...like JNF mentions above with Jalyn. All this is another subject.

Robert

I felt the same way fairwind.....but my Onc explained to me even if I became Hormone refractory....it would still be a good idea to stay on HT as it will work with much of the cancer. I also was concerned with burning up two things at once.....but I started HT first and it was the HT that brought the PSA down.....not so much the IMRT. So they felt hitting it hard with multiple treatments was the best way to go for a younger guy with good health.

Not sure if thats the best way to go but it seems multiple treatments at once is the thing a lot of Oncs believe in. Im now on Lupron/Xofigo/Xgeva and Xtandi.

Only regret is that I waited too long before I started Provenge so I never qualified for it as I was on pain meds. I believe Provenge should be one of the first treatments with high risk ....not wait for Mets. By the time I knew I had Mets....I was in severe bone pain and have been on narcotics ever since. They wont treat you with provenge while on them.

I just took a look at the presentation itself, and the discussion afterwards by D'Amico of Harvard Medical school. I think there might be some evidence in that research that extended ADT helps intermediate risk patients, not just high risk patients, even though the effect is not statistically significant.

The full presentation at ASTRO can be viewed online. There is no pay-wall. Go to this page: /www.astro.org/Meetings-and-Events/2014-Annual-Meeting/Virtual-Meeting-Preview.aspx. Click on "view the plenary session" then skip forward to about 18 minutes.

Here is the issue: For intermediate-risk patients there is no advantage to long term ADT over short term ADT until you get out to the point of 7 years after treatment. But at that point, the two curves diverge noticeably on all the measures tracked (BPFS, PCSM, and OS). I think that as the researchers continue to track the patients over a longer terms, this will become significant. In addition, Dr. D'Amico of Harvard did a commentary, and in his commentary he split the intermediate patients into favorable and unfavorable segments and said the unfavorables would probably be better off with extended ADT.

I've posted screen grabs here of the relevant slides so you can see for yourself.

Post Edited (proscapt) : 9/28/2014 6:55:18 PM (GMT-6)