Secondary Analysis of RTOG 9408

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Chartreuse Wombat

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In case anyone had to double-check their definition of UIR disease:

"Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥50%, or multiple intermediate-risk factors (IRFs; cT2b–c, prostate-specific antigen [PSA] 10–20, or Gleason score 7). "
 
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Confirms what we were all (probably) doing (and what NCCN recommended). It's a useful confirmation of our practice.

UIR is the same as it was in the original Zumsteg/Zelefsky retrospective analysis.

*waits for scarb to talk about confirmation bias for 6 paragraphs*
 
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Is anyone concerned that the prescription dose on this trial was 66.6 Gy in 1.8 Gy fraction to an isocenter 2D? In other words has nothing to do with contemporary XRT. I don't think this answers the question (and no ACM difference btw). Need to wait for RTOG 0815.

Plus how can there be more PCSM than DM in the UIR group (Figure D and E)?
 
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Is anyone concerned that the prescription dose on this trial was 66.6 Gy in 1.8 Gy fraction to an isocenter 2D? In other words has nothing to do with contemporary XRT. I don't think this answers the question (and no ACM difference btw). Need to wait for RTOG 0815.

Plus how can there be more PCSM than DM in the UIR group (Figure D and E)?

" Notably, given Gleason score inflation,6 improvements in radiation delivery, and advances in imaging over the last
25 years, it is likely that ADT would have even less benefit to contemporary patients with FIR than those enrolled in RTOG 9408.
"

Maybe ADT made up for suboptimal radiation. Maybe not.
More evidence to avoid it but still don't think you can make a blanket statement that it is inappropriate for all FIR at this point. PCSM of 9% with ADT vs. 14% without ADT was interesting.
 
@Chartreuse Wombat
If your argument is that UIR also doesn't need hormones and the dose-escalation above 66.6 is what's necessary to prove that, then OK, fair enough, let's wait for results of 0815.

I imagine, since this trial was conceptualized in 1994 and has taken 25 years to reach this point, we'll have a potential answer to that question in 2008 + 25 = 2033.

Unless something else comes out before then that changes our practice for UIR patients in the next 13 years.

But I suppose my point was that hormones in FIR should be dead in the water... at least in my practice.
 
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@Chartreuse Wombat
If your argument is that UIR also doesn't need hormones and the dose-escalation above 66.6 is what's necessary to prove that, then OK, fair enough, let's wait for results of 0815.

I imagine, since this trial was conceptualized in 1994 and has taken 25 years to reach this point, we'll have a potential answer to that question in 2008 + 25 = 2033.

Unless something else comes out before then that changes our practice for UIR patients in the next 13 years.

But I suppose my point was that hormones in FIR should be dead in the water... at least in my practice.
My point was that the patients on the no ADT arm do horribly. Given the time of accrual grade and stage migration surely play a role but compare the PCSM at 8 years (eyeballing) in either group (13% FIR 23% UIR) to the PCSM at 8 years reported on RTOG 0126 (2% in 79 Gy arm 4% in 70 Gy arm). Maybe scarb can work his magic and overlay the curves.

To reiterate patients with UIR did horribly and the event rates are nowhere near what we would expect with contemporary techniques.
 
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Fair enough - I can get behind that, and knowing what we know about benefits of dose escalation above 66.6Gy, I'm not completely surprised.
 
More evidence to avoid it but still don't think you can make a blanket statement that it is inappropriate for all FIR at this point.

What criteria do you use when recommending (or not) ADT in FIR?
 
What criteria do you use when recommending (or not) ADT in FIR?

All of it.

For instance if you have a healthy young patient with borderline FIR vs. UIR disease or anything else that may suggest more aggressive disease (with whatever criteria you want, PSA near 10, samples near 50%, cT1c but significant bilateral disease on biopsy, an MRI demonstrating questionble T3 disease, etc), I think it's reasonable to have the discussion, especially if they indicate a desire to do everything possible. And probably not unreasonable to have discussion for all FIR. I may not strongly recommend it, but I'm not sure I would refuse it if a young healthy man with a grade group 1 and PSA of 15 came to me and said he really wanted it because his father and all his brothers died from prostate cancer. I could be wrong. I don't know.
 
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