Australian study on radiation to mets.

Interesting, is this challenging the the TOAD study in some way? That trial concluded
"Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention"?

Tall Allen probably understands this and maybe will comment.

For those interested here is a link to the full study results:
Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial

In this country, long before the Varian True-Beam LINAC seen in the photos was available, the insurance companies decided spot-treating mets was not effective and they refused to pay for it....But now, with this new equipment available, and the fact that it can zap multiple mets with one treatment, this opens up a whole new approach to cancer treatment...

Snuffy Myers----- "Find it and kill it"

That was his advise for treating advanced prostate cancer.....I think that's as good a plan as any but the devil is in the details and of course, and who is going to pay for it...I bet the Aussies keep that True-Arc operating 24 hours a day..

Jerry,

here is another study with very similar results: https://euoncology.europeanurology.com/article/S2588-9311(18)30044-0/fulltext

Since the treated patients always seem to recur after about one year, I think one should combine this treatment with an intermittent ADT. This may result in holidays of several years though if you repeat the radiation to lower the PSA value again.

George

Thanks George. Kind of a mixed bag there, it seems.

Really, by the criticisms, both TOAD and ELAAT seem to have little value in guiding decision-making. With the accrual problems and limited results, with short follow up, neither one is very helpful. And it seems that combining them is even worse. So it seems one needs to look elsewhere. There are other studies that have shown for certain types of cases, especially G9+ diagnoses or those recurring with short doubling times, immediate ADT is beneficial. I have a couple of links I'll try to find later today, though maybe they're not all that great either.

That EU study suggesting delaying ADT is asking us to roll some big dice.

First, they suggest looking at local salvage therapies. The side effect profiles of all of them are simply unacceptable to me. Cryo, surgery, HIFU, all are likely to have serious QOL impact especially post primary RT. No thanks. ADT does too, but I have experience with ADT. In my particular case, a G9 cT3a, it's unlikely that any recurrence will be sufficiently local to warrant those treatments. Maybe they'd make sense for others.

Second, they're saying early ADT would slow the development of detectable metastases. Thus if you happen to be oligometastatic you wouldn't know it. Rather, they suggest no ADT, let the cancer grow until detectable, in the hope of being oligometastatic and then zapping the identified tumors with localized therapy to avoid ADT. Man, I don't know. What percent of recurrences are oligo types? That's a serious gamble, IMHO.

Third, they make a similar argument for earlier abiraterone and docetaxel. Those are typically for metastatic cases, so unless you let your cancer progress until it's detectable by radiography those aren't available. Well doesn't that raise obvious questions? Which approach would yield longer survival? Early ADT, slow the development of detectable tumors, with eventual use of those therapies? Or, just let the cancer run up until it's detectable, then use those therapies earlier? If one is truly terrified of ADT, then maybe the latter approach would be preferred. (I didn't like ADT, really didn't like it, for 3 years I didn't like it, but I'm not afraid of doing it again.)

It seems impossible to find clear, reliable studies. So many factors, so many agendas, so many limitations, so many interpretations of the tea leaves. How the cohort is selected, how the cases are grouped, how the statistical analyses are done, all shape the eventual conclusions. If we like the conclusions, why then it's a good study. Very hard to find anyone anywhere that is objective; after all, he who pays the piper calls the tune. We inescapably view the world from our own eyes, our own preferences, biases, experiences.

Redwing,

to my knowledge there is no good study which tells you what the right time to start lifelong ADT is. Of cause it depends on the individual situation of the patient.
Dr. Mitin, who presented the pooled TOAD and ELAAT abstract at the recent ASCO, said you could find some orientation using the Crook trial of intermittent ADT: https://www.nejm.org/doi/full/10.1056/NEJMoa1201546

This started ADT at a PSA value between 10 and 15.

George

Here are a couple of links on this topic. These aren't necessarily great studies. They're based on cases from quite a while ago, and some are retrospective (inherent biases). In some of the older studies, it's possible that ADT was more effective due to the lower radiation doses they could safely deliver back then. It may not be such a big deal today. Also, if one has the "triple play", the very high effective dose to the prostate may really help reduce the need for ADT. They've learned a lot about the alpha/beta ratio, or radiation dose rate sensitivity, of prostate tissue. Today's radiation protocols may hit the prostate with a lot higher dose in a shorter time as a result. Again, for localized PCa, such effective radiation should reduce the rate of recurrence.

Anyway, for what it's worth, these are a few studies I've found along the way talking about early or late ADT, and continuous vs intermittent ADT, for high risk cases or short doubling times on recurrence.

Treat earlier with ADT or not:
2003 study:
Validation of a treatment policy for patients with prostate specific antigen failure after three‐dimensional conformal prostate radiation therapy
" In the group of men with PSADT < 12 months, the median time to distant failure was significantly longer in the men who received AD therapy (6 months vs. 25 months; P = 0.02)."

2007 study:
Rising PSA in Nonmetastatic Prostate Cancer
"While both studies suffer from the limitations of retrospective series, and thus, the delayed and early hormonal therapy arms may not have been balanced, both studies did suggest that early therapy is better—at least in high-risk men."

And, as long as we're kind of on the topic: Intermittent vs Continuous ADT:
2014 study:
Intermittent versus continuous androgen deprivation therapy.
". If using ADT in the setting of biochemical relapse, intermittent ADT should be strongly considered over continuous ADT, except perhaps in patients with Gleason score of 8 or higher. "

2012 study:
Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy, with an appendix indicating:
Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy, non-inferior to continuous, but some asterisks for G8-10: "...the approximately 14 month greater median survival for Gleason 8-10 receiving CAD (continuous AD) suggests caution in this group."

Once again, the media makes claims that the researchers never did. So the 2-year distant met free survival was 39% - what would it have been without zapping the mets? I would guess - just about the same. PC progresses very slowly at this stage anyway. Ost found that 3-yr distant met free survival (on 119 patients) was only 15% at 5 years. One can't conclude that there was a benefit from this.

Ost recently published a small (n=62) controlled study in which he found that zapping mets allowed him to delay ADT by 8 months, but only if one is willing to accept 80% confidence (it is almost always 95%), and use of ADT was defined as one new distant met in those who did not get zapped, while 3 new mets were required for those who did get zapped.

/pcnrv.blogspot.com/2017/12/metastasis-directed-therapy-for.html

Dr. Ost wrote to me, "MDT does not replace ADT and our results should not be interpreted in that way." See also Stephen Strum's comments.

The TOAD and ELAAT studies are irrelevant here - in those studies, men with detected mets were mostly excluded (The TOAD study (n=293) did include a very small cohort of 32 men who were not recurrent and may have had asymptomatic mets). Detection of mets is always considered a reasonable cause for starting ADT. Also, note the divergence of the combined Kaplan-Meier after 5 years (Fig 2). 5 years is just not long enough to draw conclusions about survival after recurrent PC. We know that median survival is 13 years.

Back in 2010 I had Proton therapy which resulted in biochemical failure. Signed up for the Avastin+ATD2 trial which resulted in low but gradually increasing PSA for several years. Last year PSA reached 3.6 and it was time to do something. I got a DCFPyl PET/CT scan that indicated hot spots in my iliac lymph nodes. On to the ORIOLE trial where they zapped (at technical term) my lymph nodes via SBRT.

My current PSA is 0.3 and still dropping. Haven't had ADT since early 2012. Now, I know I'm a data point of one, but I'm happy!

Complete details including Gleason, staging and PSA history are in the "View Image" below.

...Jerry