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Another "duration of ADT during RT" question

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Posted 8/27/2017 3:30 PM (GMT 0)
Recent threads reflect common duration times for post-RP HT to be between six months and three years, with an 18 month optimum duration coming out on top for cases of ADT and SRT. Initially I was predicted to be on Lupron for six months, which was extended to nine months due to incontinence, then finally up to one year now that I have finally started ART. All of these time frames basically spanned two months prior to, two months during RT and two months following the conclusion of RT.

Many articles I've found reference a study at U of M which found "Among the factors yet to be learned are the optimum duration and timing of the added ADT. In a retrospective study, Jackson et al. at the University of Michigan reported 5-year incidence of distant metastases was 6% if they received more than 12 months of additional ADT after SRT, but 23% if they received less than 12 months of additional ADT. In fact, every month of ADT was associated with a 10% reduction in biochemical failure, distant metastases, and mortality."

My RO has stated that some studies support six months and others twelve months, but to me it seems that an additional six months might be beneficial, bringing me up to 18 months. Currently I am scheduled for a total twelve months, or three months following the conclusion of RT. I hate the SE's of ADT but have learned to cope. Do you think that perhaps I should encourage my RO to extend my ADT to 18 months? Frankly I am torn on this and would appreciate others' opinions. Thank you!
Posted 8/27/2017 4:15 PM (GMT 0)
RobLee-

I've run into the same issue for my SRT.

The RO I initially met with at Sylvester wanted 3 years. I chose Cleveland Clinic and that RO thought 6-9 months would be enough. However, after I completed SRT the RO Cleveland Clinic changed his tune and said 2-3 years.

I'm still seeing the RO at Cleveland Clinic every 3-4 months but am also seeing an MO at Sylvester who is saying about 3 years.

Good luck!

Bobby Mac
Posted 8/27/2017 4:54 PM (GMT 0)
Thanks Bobby Mac. I've also heard two years and three years, with my RO being the one who says six to twelve months. I'm inclined to think that longer is old school thinking and shorter is the newer thinking.
Part of me suspects that a little longer may be better for my own personal outcome, while the other side of me says just let the doctor do what he does.
Posted 8/27/2017 5:16 PM (GMT 0)
RobLee-

This issue is discussed in the following article. It includes the UMich study (which was not a randomized trial) as well as several others.

/pcnrv.blogspot.com/2016/08/combining-androgen-deprivation-therapy.html

As you see, there are no standard answers. Your pathology and your initial PSA with its doubling time have to be considered.

18 months is not "optimum" - we have no idea what optimum is, and it will likely be different depending on patient disease characteristics. 18 months came up in a study by Nabid et al. that showed that outcomes of primary radiation therapy were no different with 18 vs 36 months of Casodex (not Lupron). It does not apply to your case. However, one can conjecture that if 18 months of Casodex was no worse when used for primary radiation, maybe 18 months of Lupron is no worse when used with adjuvant/salvage radiation. It sounds plausible to me, but arguments for not applying it sound plausible to me too.

I think you have to go with whatever makes you feel most comfortable. You used bold type in your signature to highlight your T3b stage and Gleason score, and you are right that those are troubling risk factors. So are your high and rising initial PSAs. Based on those, and if the side effects are tolerable, I think you are justified in wanting a longer course of adjuvant ADT, and two years is certainly within what many ROs would consider to be reasonable.
Posted 8/27/2017 5:21 PM (GMT 0)
Rob,

the 18 months start when the RT begins. So you would have to stop ADT in February 2019. ADT before radiation is called neoadjuvant ADT and following RT is adjuvant ADT. The 18 months are suggested for adjuvant ADT.

Radiation damages the DNA of the tumor cells and these will die when they try to split again. This can take more than a year to happen. However, tumor cells in part can repair the DNA. One possible reason for the benefit of ADT combined with RT has recently been reported in a study. The researchers write that ADT can block this DNA repair. So you should be on ADT for 18 months after RT.

George
Posted 8/27/2017 5:21 PM (GMT 0)
RobLee-

Yes, it seems SRT and length of ADT is not black and white. I am a GS7 (4+3), persistent PSA of 2.4, with a positive lymph node found on a 68 Gallium PSMA scan so I guess for me more is better. How long? Not sure, but I figure at least 18 months and see how I feel then.

Bobby Mac
Posted 8/27/2017 6:17 PM (GMT 0)
No recommendation, just a comment my nationally-prominent MO (a name many here might recognize) made when I was wanting to quit at 2 years. Keep in mind this was in mid 2015, and some studies have been published since then. Notably, a Dr. Nabid has done a lot on the topic, so his work may be good enough to trust. Others can comment on that. Here's one of his recent items, take it for what it's worth. Looks pretty encouraging though:

ADT+RT duration can safely be shortened in high risk PC.

She said, "I'd rather find out 10 years from now that 3 years was too much, rather than that 2 years wasn't enough." She also pointed out that there is a lot of discussion about HT duration in breast cancer. But, they're debating how much longer to continue it!

I'm not sure if HT is worse for men than for women. It really devastates who and what we are as men, though. I didn't like it, won't like it if I have to do it again. My G9 is a worst case scenario, and most likely to benefit from longer ADT.

Still, to this day, the point is argued by many.
Posted 8/27/2017 6:35 PM (GMT 0)
Redwing,

in the article you cited: "ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months".

So the Nabid study is not based on Casodex only!

George
Posted 8/27/2017 7:08 PM (GMT 0)
You're right, but that study was for high risk patients only - not for adjuvant/salvage RT. The RT included whole pelvic radiation, and only 70 Gy (80 Gy is now standard for high risk patients.)

meetinglibrary.asco.org/record/80086/abstract

I was thinking of RTOG 9601, which was a randomized clinical trial of casodex + SRT vs SRT only, and the Casodex was given for 2 years. Recurrence-free survival, metastasis-free survival, prostate cancer specific survival, and overall survival were all improved by the 2 years of Casodex. However, the radiation dose was only 64.8 Gy. Would it have the same benefit if 70 Gy were used? If Lupron were used? If it were used for a different duration? If it were used for ART rather than SRT?

www.nejm.org/doi/full/10.1056/NEJMoa1607529#t=article

The only randomized trial on duration of ADT for SRT we've had so far is the one in that article - so all we know is that 6 months is better than nothing with the sub-optimal radiation doses they used. The UMich and King's analyses suggest that longer might be better, but there is no definitive data. This is very much a judgment call.
Posted 8/27/2017 10:33 PM (GMT 0)
How often do they test PSA after radiation is done? If the hormone therapy is stopped, is there a rule for when it should be restarted? My new RO is in favor of the intermittent plan, saying continuous deprivation is old thinking, but he didn't show me any papers to study.
Posted 8/28/2017 12:47 AM (GMT 0)

George_ said...
Redwing,

in the article you cited: "ADT included a 50 mg initial dose of bicalutamide daily for 1 month plus 10.8 mg of subcutaneous goserelin every 3 months".

So the Nabid study is not based on Casodex only!

George

I'm probably missing something; was someone suggesting Casodex only? That's not done as a monotherapy, at least not in the USA. Casodex at 50mg/day is usually to stop the initial flare of testosterone when starting Lupron or similar LHRH agonists, and it's not always needed.
Posted 8/28/2017 6:18 AM (GMT 0)
Redwing,

I mentioned this since Allen wrote regarding the Nabid study: "...with 18 vs 36 months of Casodex (not Lupron)". He corrected that in the following post.

George
Posted 8/28/2017 11:04 AM (GMT 0)
Oh i see. Thanks. I don't see all of the posts on the forum.
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