Just curious as to what dose you guys go to for definitive prostate, and if you're in the 79.2+ camp, do you cheat at all around rectum? We treated to 81 Gy to PTV with the caveat that posterior coverage was constrained to ensure max dose of around 81-82 to prostate/rectal interface.
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deleted4401
75.6 for low risk, 77.4 for intermediate risk with 6 months ADT, 77.4 with 2.5 years ADT for high risk. Arbitrary, somewhat. In residency, did 75.6 Gy for almost all cases. And, all the dose escalation trials, the highest dose was 79.2, but that was to isocenter, so even my 75.6 gets me there.
When you do 81+, is that to PTV? How much of the PTV gets prescription? Why go so high? Not saying you shouldn't, just wondering rationale. Some of my colleagues are going higher, too.
Looking biologically, the failure pattern for high risk patients is predominantly distant, so I just wonder why go much higher.
Honestly, prostate sort of bores me. I mean, for low-risk, I could recommend skiing or playing the bongos, and the prostate cancer specific survival will be very high at 10 years.
When you do 81+, is that to PTV? How much of the PTV gets prescription? Why go so high? Not saying you shouldn't, just wondering rationale. Some of my colleagues are going higher, too.
Looking biologically, the failure pattern for high risk patients is predominantly distant, so I just wonder why go much higher.
Honestly, prostate sort of bores me. I mean, for low-risk, I could recommend skiing or playing the bongos, and the prostate cancer specific survival will be very high at 10 years.
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The dose per fraction is also an important factor to take into account.
Lots of people (probably the majority in the US?) give 1.8 Gy/d, while in Europe we often give 2 Gy/d.
If one believes in the theory describing very low alpha/beta values for prostate cancer cells, then 2 Gy rather than 1.8 Gy /d would mean something like an extra 3-4 Gy BED.
We currently give 74 Gy in 2 Gy fractions/d and don't cheat anywhere.
Lots of people (probably the majority in the US?) give 1.8 Gy/d, while in Europe we often give 2 Gy/d.
If one believes in the theory describing very low alpha/beta values for prostate cancer cells, then 2 Gy rather than 1.8 Gy /d would mean something like an extra 3-4 Gy BED.
We currently give 74 Gy in 2 Gy fractions/d and don't cheat anywhere.
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For low and low-intermediate risk I use 70 Gy in 2.5 Gy fractions. For intermediate and high risk I use 78 Gy in 2 Gy fractions.
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Some of us in the US are concerned regarding late rectal toxicity (albeit that's 3D rather than IMRT data) with using > or = 2 Gy/day for treating prostate.
Some however are like GFunk. I know that MD Anderson likes those bigger 2-2.5 Gy fractions. The hypofx data (70 Gy/28 Fx) looks pretty reasonable. But I guess we're just a product of our training and comfort zones 🙂
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I've rotated on prostate several times at a few different institutions. It's interesting to see the range of treatments. For those with access, I thought Efstathiou and Horowitz had a great summary talk at ASTRO last year:
http://www.softconference.com/ASTRO/sessionDetail.asp?SID=312525
There is a survey of 20 different cancer centers, their doses, constraints, IGRT, etc...
We have a very active HDR brachytherapy service. But, for external beam alone, we go to 79.2Gy for low risk, 81Gy for high risk based on the highest dose in the Zelefsky dose escalation series (http://www.ncbi.nlm.nih.gov/pubmed/9635694) with VMAT and IGRT (usually fiducials, sometimes CBCT). I think 78 based on Kuban or 79.2 based on Zietman are also perfectly reasonable. MSKCC is doing 85.6Gy routinely, but the data so far has not shown benefit to that high a dose. I think we could get away with it if we needed to with VMAT.
CTV includes 1cm of prox SV. Our PTV is 0.5 cm posteriorly, inferiorly, and superiorly and 0.7 cm anteriorly, and laterally. We usually have 98% PTV coverage to that dose. We keep hot spots off the rectum obviously. Personally, based on the ARRO Zelefsky talk I like to keep high dose (say 75.6Gy) to half of the rectum on a given slice.
In my experience it's impossible to compare one site to another as far as constraints and dose volumes. Everyone contours prostate, SV, and rectum differently. Our constraints are tighter than RTOGs, but we contour a smaller rectum. We get 81Gy to the anterior rectum on most plans, but certainly try to avoid higher than 82Gy. I've seen other guys contour rectum practically up to prostate (and without MRI how can you really tell?) and their constraints are a little different.
ADT data in intermediate is weak. They were included in several trials, but the treatment doses were low. We don't treat with ADT for most intermediates. There is a range of opinion on this of course. I liked this recent article (Zelefsky) on the topic: http://www.sciencedirect.com/science/article/pii/S1470204512700840. RTOG 0815 is addressing this topic (modern radiotherapy +/- 6 months ADT), but we won't have that data for a long time. Either ADT or not with external beam seems reasonable at this point.
For high risk beam alone I don't think anyone argues with 28 months - 3 years ADT (RTOG 9202 or EORTC/Bolla). Whether to radiate pelvic nodes to 45Gy is still up in the air though (RTOG 9413 seems to have morphed into 0924).
http://www.softconference.com/ASTRO/sessionDetail.asp?SID=312525
There is a survey of 20 different cancer centers, their doses, constraints, IGRT, etc...
We have a very active HDR brachytherapy service. But, for external beam alone, we go to 79.2Gy for low risk, 81Gy for high risk based on the highest dose in the Zelefsky dose escalation series (http://www.ncbi.nlm.nih.gov/pubmed/9635694) with VMAT and IGRT (usually fiducials, sometimes CBCT). I think 78 based on Kuban or 79.2 based on Zietman are also perfectly reasonable. MSKCC is doing 85.6Gy routinely, but the data so far has not shown benefit to that high a dose. I think we could get away with it if we needed to with VMAT.
CTV includes 1cm of prox SV. Our PTV is 0.5 cm posteriorly, inferiorly, and superiorly and 0.7 cm anteriorly, and laterally. We usually have 98% PTV coverage to that dose. We keep hot spots off the rectum obviously. Personally, based on the ARRO Zelefsky talk I like to keep high dose (say 75.6Gy) to half of the rectum on a given slice.
In my experience it's impossible to compare one site to another as far as constraints and dose volumes. Everyone contours prostate, SV, and rectum differently. Our constraints are tighter than RTOGs, but we contour a smaller rectum. We get 81Gy to the anterior rectum on most plans, but certainly try to avoid higher than 82Gy. I've seen other guys contour rectum practically up to prostate (and without MRI how can you really tell?) and their constraints are a little different.
ADT data in intermediate is weak. They were included in several trials, but the treatment doses were low. We don't treat with ADT for most intermediates. There is a range of opinion on this of course. I liked this recent article (Zelefsky) on the topic: http://www.sciencedirect.com/science/article/pii/S1470204512700840. RTOG 0815 is addressing this topic (modern radiotherapy +/- 6 months ADT), but we won't have that data for a long time. Either ADT or not with external beam seems reasonable at this point.
For high risk beam alone I don't think anyone argues with 28 months - 3 years ADT (RTOG 9202 or EORTC/Bolla). Whether to radiate pelvic nodes to 45Gy is still up in the air though (RTOG 9413 seems to have morphed into 0924).
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deleted4401
Good information! Thanks, Neuronix. Still can't get myself to do the 70 Gy/28 fx. Anyone doing x'treme hypofx - 5 fractions? Any new data out on that, yet?
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We introduced daily CBCT 4 years ago for prostate cancer treatment in our clinic.
Since then we have seen rather big mean errors in positioning, with the prostate shifting several mm (often more than the typical 1cm margin). We match on the prostate (not the bone!). I am rather confused by this and questioning myself how often I have actually treated the rectum and not the prostate, when delivering standard 3D-RT without CBCT or fiducials, matching simply on the bone on weekly portals 4-7 years ago.
The question rises thus:
Are the results in better biochemical progression free survival through dose escalation based on the dose escalation itself over the "standard levels" of 70-74 Gy or is it just that you have more chances to actually hit the tumor itself with more fractions? Please remember that all the data on dose escalation coming from randomized trials are based on non-CBCT / fiducials trials.
Thus the question may be, if "standard dose" EBRT with 70-74 Gy, delivered with daily CBCT / fiducials / Calypso may be as good as "blind"
EBRT to 80+ Gy in terms of bPFS, because (for a change) we actually hit the tumor every day...
😕
Perhaps 81 Gy with daily CBCT / fiducials / Calypso are an overkill? There were some data showing that the dose-response curve over 80 Gy actually becomes flat in prostate cancer (if I am not mistaken), but can't recall that publication.
Since then we have seen rather big mean errors in positioning, with the prostate shifting several mm (often more than the typical 1cm margin). We match on the prostate (not the bone!). I am rather confused by this and questioning myself how often I have actually treated the rectum and not the prostate, when delivering standard 3D-RT without CBCT or fiducials, matching simply on the bone on weekly portals 4-7 years ago.
The question rises thus:
Are the results in better biochemical progression free survival through dose escalation based on the dose escalation itself over the "standard levels" of 70-74 Gy or is it just that you have more chances to actually hit the tumor itself with more fractions? Please remember that all the data on dose escalation coming from randomized trials are based on non-CBCT / fiducials trials.
Thus the question may be, if "standard dose" EBRT with 70-74 Gy, delivered with daily CBCT / fiducials / Calypso may be as good as "blind"
EBRT to 80+ Gy in terms of bPFS, because (for a change) we actually hit the tumor every day...😕
Perhaps 81 Gy with daily CBCT / fiducials / Calypso are an overkill? There were some data showing that the dose-response curve over 80 Gy actually becomes flat in prostate cancer (if I am not mistaken), but can't recall that publication.
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Well, technology has changed since 9406 was published. We all use IMRT and some form of advanced IGRT (CBCT, fiducials, U/S, radio waves). Also, I find that our rectal/bladder constraints are routinely superior to RTOG published guidelines.
Neuronix said:
This article was referenced at the ASTRO Spring Refresher last year for when to add ADT in intermediate risk and I stick with those guidelines. Basically primary Gleason 4 or > 50% of cores positive.
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That's true. I remember when I first started training, we tried to keep our 70 Gy constraint to under 25% of the rectum. Now it's <20% and routinely I see plans well under that even.
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Agree with Palex that a component of the benefit of dose escalation is more opportunities to hit the target.
I do fiducial marker match and fuse an MRI in tx position for planning. Most commonly prescribe to 79.2Gy/44 with 98% PTV coverage, but will drop one or two fx to improve rectal DVH in a minority of cases. I don't believe in "cheating" on PTV margins, even posteriorly. Most prostate cancer is in he posterior-lateral gland, so you are essentially cheating on the area most likely to harbor disease. Without cheating, It is nearly impossible to reproducibily keep the rectal max <81-82Gy if prescribing to 79.2Gy. That said, I'm not aware of any data correlating voxel max dose with late grade 2+ proctitis or ulceration/fistula risk. I constrain anterior rectal wall to max <84Gy, but admittedly it's a made up constraint. We are much more rigorous about keeping the V70 <15% (and <10% in vast majority of cases). Also look at V64 (target <17%) and V40 (target <35%), which are adopted from the Fox Chase constraints used in the Alan Pollack era.
Agree with GFunk about the rationale for hypofrac. We used 70/28 where I trained. I'm waiting for RTOG 0415 to be reported, but will readily adopt for low risk patients if equivalent in that trial. In the available trials of moderate hypofractionation, there doesn't appear to be an increased risk of late GI toxicity. The Fox Chase trial did, however, suggest an increased risk of GU toxicity with hypoactionation (70.2/26) for patients with IPSS/AUA score > 10.
I do fiducial marker match and fuse an MRI in tx position for planning. Most commonly prescribe to 79.2Gy/44 with 98% PTV coverage, but will drop one or two fx to improve rectal DVH in a minority of cases. I don't believe in "cheating" on PTV margins, even posteriorly. Most prostate cancer is in he posterior-lateral gland, so you are essentially cheating on the area most likely to harbor disease. Without cheating, It is nearly impossible to reproducibily keep the rectal max <81-82Gy if prescribing to 79.2Gy. That said, I'm not aware of any data correlating voxel max dose with late grade 2+ proctitis or ulceration/fistula risk. I constrain anterior rectal wall to max <84Gy, but admittedly it's a made up constraint. We are much more rigorous about keeping the V70 <15% (and <10% in vast majority of cases). Also look at V64 (target <17%) and V40 (target <35%), which are adopted from the Fox Chase constraints used in the Alan Pollack era.
Agree with GFunk about the rationale for hypofrac. We used 70/28 where I trained. I'm waiting for RTOG 0415 to be reported, but will readily adopt for low risk patients if equivalent in that trial. In the available trials of moderate hypofractionation, there doesn't appear to be an increased risk of late GI toxicity. The Fox Chase trial did, however, suggest an increased risk of GU toxicity with hypoactionation (70.2/26) for patients with IPSS/AUA score > 10.
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Thank you, I was unaware of that study. I also ran into the same risk factors in a new report from MSKCC in press in the red journal:
http://www.ncbi.nlm.nih.gov/pubmed/22981709
May be time to rethink that position for me.
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Good group for RTOG 0815.
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How do you guys consider medical comorbidities in determining the recommendation for length of ADT (or to do ADT at all). Cardiac disease seems to be the big concern for the possible risk of ADT. Does it make you just consider doing 6 months as opposed to 2-3 years in the high-risk folks or just avoiding it altogether, even in the high-intermediate risk groups?
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I think the risk of cardiac toxicity with ADT was/is massively overblown. In older RTOG studies there was an OS benefit with long-term ADT in the high-risk group.
Also, this article in JAMA (2011) definitely answered the question.
The only caveat is when you have a patient that is extremely high risk (e.g. s/p CABG, HTN, DM2, obese); you have to weigh the potential OS benefit with his expected natural life span and the morbidity of ADT.
Also, this article in JAMA (2011) definitely answered the question.
The only caveat is when you have a patient that is extremely high risk (e.g. s/p CABG, HTN, DM2, obese); you have to weigh the potential OS benefit with his expected natural life span and the morbidity of ADT.
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If they're not already on 0924
We haven't even touched on whole pelvis yet...I've seen different people do different things. I think with the JAMA meta-analysis it seems reasonable to give ADT regardless of comorbidities as long as someone is monitoring for the other side effects like rising blood glucose in diabetics or osteoporosis. To me the D'Amico trial (http://jama.jamanetwork.com/article.aspx?articleid=1149299) makes sense that cormobidities affect survivial benefit. First, it was a smallish trial that was likely underpowered in that subgroup analysis (p was still trending in Figure 2...), second, those patients die of their comorbidities more often, so the benefit of treating their prostate cancer will be less.
So for patients who are high risk and have significant comorbidities, they still deserve treatment. I have a quality of life discussion with them. If they have no sexual function and desire as it is and they want to maximize their chances of not dying of prostate cancer, I figure I might as well give them the 32 +/- 4 months of hormones. If QOL by way of sexual function and freedom from hot flashes is super important, I would still consider no ADT at all be reasonable in that subgroup. I do consider 6 months as something of a misnomer considering in the elderly it often takes 6 months to 1 year for return of testosterone to low normal levels. You're really assigning them 12-18 months of ADT related side effects. It's still reasonable to do so, but thinking about it that way makes me more apt to accept no ADT in that select case.
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Recent JAMA meta-analysis showed no increased risk of CAD/fatal MI with ADT. I think that the D'Amico//Harvard study was an outlier. Cardiac risk isn't reproducibly increased in RTOG experience or in other cooperative group trials. Also, no apparent difference in risk of MI based on ADT duration in RTOG 9202, EORTC 6mo vs 3yr, or in combined analysis of Harvard/TROG/Canadian trials. RTOG 0815 collecting ACE-27 comorbidity indices on all patients to see if that is predictive of benefit and ADT morbidity in larger, cooperative group trial.
For patients with severe CAD (STEMI in last 6mo, NYHA class 3-4 CHF, etc), will omit ADT for intermediate risk. Otherwise, I offer eligible IR patients enrollment on 0815. If they decline, I think that 4+3, >50% of cores or multiple intermediate risk features (high risk based on MSKCC stratification) are reasonable criteria.
I never omit ADT in high risk. For elderly paients (>70) with clinically-localized, low volume, low PSA, Gleason 8 dz, will do 6mo ADT. For all other high risk or locally advanced pts, doing 2-3 yrs ADT regardless of cardiac RFs.
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If they're not already on 0924
Whole Pelvis !?!?
Gimme a break....how many negative randomized trials does it take?
Currently at 3 and counting...
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Thanks for the replies!
Didn't know about the ADT meta-analysis in JAMA (funny that some of those authors are from the same institution as D'amico)
Didn't know about the ADT meta-analysis in JAMA (funny that some of those authors are from the same institution as D'amico)
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Does anybody else struggle with ADT duration recs for clinically localized, high risk pts?
The NCCN recommends long term ADT for high risk patients, so it is definitely a defensible practice. That said, the trials comparing short term vs long term (RTOG 9202 and Bolla) were limited to patients with locally advance or node positive (Bolla) disease. RTOG 85-31 included only T3 or node positive. The first EORTC/Bolla trial using 3yrs of ADT included pts with T1-2 WHO grade 3 dz, but only 9% of the 415 pts (37) were enrolled based on this criteria. All others had locally advanced dz. Meanwhile, the data showing a survival benefit with short term ADT in T1-2 Gleason 8-10 is fairly robust, as these patients were included in Harvard, RTOG 94-08 and TROG.
The group that I struggle with are patients with low volume, high grade disease with PSA <10 and age >65-70. Older patients take considerably longer to recover to their baseline testosterone levels based on the post-hoc analysis of the Harvard study, thereby the true duration of androgen suppression is longer in this group anyway. And even if cardiovascular morbidity isn't increased, the risks of diabetes, sarcopenia, bone density loss, fatigue and mood change/irritability are very real. Not to mention chronic erectile dysfunction.
It's easy to just reflexively recommend long-term in these patients, but I'm not sure that it is entirely data driven... At least not based on the randomized trials. Anyone else have any thoughts or insight into this issue?
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That's just it though, clinically localized (T1c-T2b) high risk were not eligible for 9202 or Bolla 2. As such, there are actually no data demonstrating a benefit of LT vs ST ADT in this subgroup. Survival benefits have been shown for both ST and LT (although limited to a very small number of pts in Bolla 1) ADT compared to RT alone in these patients, but the data is far more robust for short term based on number of these patients treated on randomized trials.
I have seen the Beaumont and Seattle data omitting ADT for high risk patients getting combination therapy. Wouldn't do that in practice though, as there are no cooperative group phase II or randomized data suggesting that you can safely do this.
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Just wondering what everyone's experience has been like with the 70Gy fractionation scheme in terms of toxicity?
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Well tolerated overall. This was our standard regimen where I trained.
I try to limit rectal V70 <5% and V64 <10%. The constraint from the well known Kupelian study using this regimen was V70 <10%. I think that they had 1 or 2 cases of rectal ulceration/fistula in that study, so I have tried to be more rigorous with rectal constraints in the small number of patients I have treated with this regimen since entering practice.
GU toxicity appears to be slightly increased among patients with moderate-severe BPH symptoms at presentation. There are data suggesting increased GU toxicity among patients with pre-tx IPSS/AUA scores >10 from the Fox Chase randomized trial.
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So, this means you are adjusting your PTV accordingly to fulfill this constraint?
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No. Use 5mm uniform margin with prostate drawn on MRI. Daily center-of-mass fiducial marker match. No PTV alterations. Haven't had significant problems meeting these constraints using those planning parameters. I think that I approved one plan with a V70 of 6%, but otherwise have been able to keep to <5%. This is feasible because of MRI-based target delineation. There is data from Mack Roach @ UCSF suggesting that the prostate is ~20% smaller when contoured on MRI compared to CT, thereby allowing for better normal tissue avoidance.
In my previous post, I was incorrect re the rectal constraint from the Kupelian study. In that study it was V70 <10cc (not 10%). That said, the vast majority of patients have rectal volume <100cc if prepped appropriately. As such, V70 <10% is actually a more conservative restraint.
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Very interesting.
How do you prep them? I've seen all kinds of schedules.
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Enema 2hrs before sim, bladder full. If rectum is inadequately prepped in first attempt (uncommon), we reschedule sim and do two enemas (8hrs before & 2 hrs before). Try to keep it simple so that it is routine and reproducible for sim techs, nurses, etc.
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I've always wondered about the benefits of doing an extensive rectal prep before the sim when you (presumably) aren't going to be doing it before every Fx. Unless you actually prep them before every Fx?
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I don't prep them before every fx, although I think that a couple institutions do. I would, however, for 5 fx SBRT if we were doing that treatment. I also don't think that a single enema is an "extensive" rectal prep for sim, nothing compared to colonoscopy prep!
Your point is well taken about questionable benefit, especially in era of fiducial-based IGRT. MDACC first reported the observation of inferior biochemical control outcomes (and lower rectal toxicity) in patients with distended rectum at sim. This study was in the pre-IGRT era. There is a more recent study from MDACC among patients treated with fiducials or CBCT-based IGRT, again demonstrating a higher rate of progression among patients with rectal distension. Not sure that I believe this data, but it is out there.
The main reason that I continue to prep patients is because it gives you a more accurate rectal DVH. In patients with distended rectum at sim, the rectal DVH is artificially improved (as rectal volume is increased). With prepped rectum, you get more challenging geometry and a resultant IMRT plan which is better optimized for rectal avoidance IMO
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Agreed that with the rectum prepped it results in a more challenging and conservative IMRT plan, with no artificial DVH improvements. However, it doesn't seem as reproducible. If they were simulated with an ideally empty rectum, when they come in for tx with the rectum not completely empty, the geometry changes with anterior displacement, and even with image guidance the rectum will get more dose than the plan initially indicated.
I like the rectum being empty, but whatever I tell them at sim is what I usually tell them for treatment.
I like the rectum being empty, but whatever I tell them at sim is what I usually tell them for treatment.
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Internal pelvic anatomy is a "unique anatomic situation" for each fraction independent of whether the patient is prepped for sim or not. This is due to minor (or not so minor) variations in rectal and bladder filling. Bladder filling is more controllable/reproducible, but rectal volume is not (without doing a daily pre-tx enema, which is pretty barbaric for a conventionally fractionated course IMO). Several studies have shown that measurable daily variation is present in the vast majority of patients: ie the pt who is prepped for sim will have a distended rectum for some fractions, and the patient who is not prepped will have an empty rectum for some fractions. That is the benefit of IGRT, it allows you to accurately localize the target independent of these variations and thereby utilize smaller margins. IMRT allows you to better avoid adjacent OARs and reduce late toxicity, particularly for the rectum. Because simulation with an empty rectum results in a more ideally optimized IMRT plan with better posterior avoidance/dose fall-off, it confers superior rectal sparing regardless of the rectal volume that day. Neither technique is wrong, I just think that the rationale for prepping patients for sim is stronger, and likely contributes to the clinical benefits observed in the MDACC studies.
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I'd like to stress out two points:
1. IGRT does allow you to perform couch adjustments to compensate for prostate movement due to bowel/bladder filling. I have however sometimes found myself correcting the couch position by >1cm at the prostate base to compensate for a full rectum, only to discover that I am missing the target in the apex region by performing such a couch adjustment. I don't know how many of you guys have Hexapod couches, but we don't.
2. IMRT has been widely introduced into treatment of prostate cancer, but let's be honest: The main reason was not because people wanted to spare patients from excessive toxicity, the main reason was purely financial. I am not certain, how robust these prostate IMRT plans are, when you are dealing with totally different anatomy on daily basis. Surely 3D-conformal plans are quite more realistic and less influenced by daily filling status of bladder & bowel. Bearing in mind that more and more people are pushing the dose to the limit in prostate cancer EBRT, creating very steep dose-falls to the rectum, can we be certain that dose-escalated IMRT without reproducible filling status in bowel & bladder is a safe treatment?
Surely people are going to point out to the thousands of patients treated by Zelefsky, etc. without any (mentioned) prepping before EBRT, but I think we should still be cautious.
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Sorry. Getting in on this discussion a little late. Regarding the length of ADT, there is an interesting multi-inst abstract from ASTRO 2008 looking at this question. http://www.redjournal.orgu/article/S0360-3016(08)01148-6/fulltext Take away is that there is a benefit to long-term over short term, but it becomes smaller over time (somewhat obvious). 1 year of ADT gets you 83% of the total bNED rate seen with 3y of ADT. When I'm in practice I will strongly encourage patients to complete 2y4m of ADT with high risk features, but if they are older, experiencing significant side effects (metabolic syndrome, severe fatigue, loss of libido, etc), and have completed >1+ year of ADT then I would consider stopping early.
Do any of the more senior contributors recall this abstract being presented? Any ideas why it is not in manuscript form (at least that I can find)?
Do any of the more senior contributors recall this abstract being presented? Any ideas why it is not in manuscript form (at least that I can find)?
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Thanks for bringing up this abstract RadSki. I attended this oral presentation at ASTRO Boston while still in residency. Not sure why it hasn't been published, as it is very interesting and relevant data generated from a large cohort (~4000) of patients.
The abstract appears to demonstrate a declining benefit of androgen deprivation over time. A closer look at the abstract, however, supports the point that I am making about patients with clinically localized disease.
In this study, the reference standard duration of ADT is 3yrs. Using this duration as a reference, 54%, 83% and 96% of the bNED benefit was conferred in the first 6mo, 12mo and 24mo, respectively. This would suggest that 6mo is inferior to 3yr, right? On closer look, however, the duration-benefit association is significatly more pronounced in patients with T3 dz (vs T1-2) and there is a trend toward association among patients treated to lower doses (<69Gy). There was no measurable benefit of long-term ADT in pts with T1-2 disease and, among patients treated with neoadjuvant and concurrent ADT, there was no appreciable benefit beyond 7mo. So again, this is another study showing a benefit on long term ADT for locally advanced (T3), with no demonstrable benefit for clinically localized disease.
This boils down to stage migration. RTOG 92-02 and Bolla 2 were performed in an era, or part of the world (in the case of Bolla 2), in which locally advanced (T2c-T4) disease is/was more common. These studies show a benefit of LT vs ST ADT; but the patients that we most commonly see with high risk disease would not have been eligible for either of these studies (or RTOG 85-31 for that matter). A typical "high risk" patient in 2013 has T1c, Gleason 8, PSA 9.7. In this example patient, there are no data to suggest superiority of long-term over short-term ADT. I think that this point has been overlooked by the rad onc community and by the NCCN. This fact is surprising given the accumulating data describing the morbidity of long-term ADT.
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I agree completely with both of these points. Neither issue, however, would be mitigated by doing rectal prep for sim (or not doing prep), as internal pelvic anatomy still varies day-to-day. These issues do illustrate the importance of using adequate PTV margins (some institutions have published reports using PTV margins of 2-3 mm around the prostate with IGRT +/- calypso beacons... Which seems a little skimpy to me). Is it possible that the greatest benefit of dose escalation, is that we more reliably get 72-74Gy to 100% of the prostate gland? I think that was suggested earlier in this thread, and very well may be the case.
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The only solution to this dilemma is probably performing daily prep, both for sim and treatment.
D
deleted4401
More on hormones for intermediate risk prostate CA in this month's Big Red:
http://www.redjournal.org/article/S0360-3016(12)00856-5/abstract
"Conclusions
Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF."
http://www.redjournal.org/article/S0360-3016(12)00856-5/abstract
"Conclusions
Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF."
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Below is a brand new article (Red J in press) from U of Mich looking at (mostly) clinically localized high risk patients treated with dose-escalated RT combined with no ADT vs ST-ADT vs LT-ADT. Patients with gleason 8-10 disease getting LT-ADT had better MFS, PCSM and ACM compared to those getting ST-ADT. There was also a demonstrable benefit on these endpoints for each additional month of ADT. Only 234 patients, but the first study to show a benefit of longer duration ADT in high risk, clinically localized patients. The authors acknowledge, however, that this benefit may not apply to the patients at highest risk due to comorbidity (hx of MI or CHF), but the numbers in this group are small. Will be interesting to see if other groups report similar findings.
Feng F, et al: Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer. Red J 2013
Also, I was able to find the Australian study which was previously referenced re: relative benefit of ADT according to duration.
PMID: 20472361
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Didn't RTOG 9202 do that too?
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I think it boils down to which era of "high-risk" we are looking at. Stage-migration has created a different set of patients now than when 92-02 was drafted and opened. TarHeel alluded to this earlier in the thread.
