Brachy boost cuts mortality in half for high risk patients

This is their follow-up study based on 1,001 high-risk patients treated at some of the top cancer treatment centers in the US. As expected, the differences are statistically significant with the larger sample size.

/pcnrv.blogspot.com/2017/02/for-very-high-risk-patients-ebrt-bt-is.html

Thanks for sharing! Question: the study states three different median follow-up periods...why the three different medians? Also, how does it work with the follow-up period being shorter than the 10-year rates they were studying? (Clearly, I wasn't a science major in school...)

Interesting. It's possible too that something a little more subtle may have happened, perhaps less definitive than saying "EBRT+BT is superior to EBRT", which is what this is clearly implying. That is perhaps something of an oversimplification.

The study says the median dose for EBRT only, in other words half had less, was 78 Gy. I believe it's been shown that older lower dose levels, limited due to toxicity, weren't as effective as today's escalated doses. In other words, doses of 75 Gy and less don't provide as much control as doses of 79.2 or 81, common today.

Here's a study, as recent as 2009, showing common RT doses at the time.

Radiation dose escalation for localized prostate cancer

That study stated: The median radiation doses were 68.4 grays (Gy) for 3D-CRT and 75.6 Gy for IMRT. That's pretty low by today's standard, and it wouldn't be surprising that BT would help by significantly increasing the local dose in the prostate.

So for the study referenced in this thread, on one hand, what percent of the EBRT only group actually had doses that would be considered inferior today? Certainly quite a portion would have, if the median is 78 Gy. The patients were treated between 2000 and 2013, so a huge range of RT capability and dose levels. All of those get lumped into the aggregate results from EBRT.

On the other hand, no doubt the EBRT+BT group had higher median dose of 90 Gy. So, half were more, half less. But, if there's a lower threshold for RT effectiveness, say 75 Gy, far fewer of them would be below that threshold. In that sense, sure, BT really helps, since it gets the whole cohort above that threshold especially with older lower dose EBRT protocols. As we've seen too, adding BT comes with a significantly increased risk of side effects like urinary strictures.

It would be interesting to further stratify the EBRT group, and compare only the ones above the effective level, say only those with 79.2 Gy and higher, vs the EBRT+BT group.

Those who believe in, and provide, brachytherapy treatments may be subject to pro-BT biases. That would be natural. It is simply worth noting that in any study one needs to consider such potential biases, particularly in retrospective studies.

I don't mean to question anyone's treatment choices. I do question studies, every one I see. It's all too easy to inadvertently draw conclusions aligned with one's confirmation biases. The good news of course is this "triple play" clearly does provide very good results.

I take the risk of being attacked for even bringing this up, but it seems worthwhile to question group-think on occasion.

For anyone interested, this article actually supports my alternative assessment:

Survival Outcomes of Dose-Escalated External Beam Radiotherapy versus Combined Brachytherapy for Intermediate and High Risk Prostate Cancer Using the National Cancer Data Base

In that article, one finds this interesting conclusion, which is directly to my point:
However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). We do know BT causes added side effect risks. So, are those risks worthwhile? Tough call.

Clear conclusions? I don't know. I do know things aren't always as they appear to be.

Michael_T:

This was a retrospective study, and not a prospective clinical trial. That means that they had as much follow-up info as they had in their records. The 10-year outcomes come from Kaplan-Meier survival curves, which show how survival changes over time, while allowing for loss of patients to follow-up. The authors also showed 5-year survival, which are more statistically robust, but I feel are a little too optimistic. The sample size was large enough in this expanded study for the differences at 10 years to be statistically significant.

Redwing-

Keep in mind that all patients were treated at blue-ribbon treatment centers that actually led the way in dose escalation. Certainly, dose escalation is the point here. The researchers are telling us that higher doses (obtained by brachy boost) was associated with better outcomes - much better outcomes.

It is certainly true that increasing the dose by a couple of Gray might improve outcomes, but would anyone seriously expect survival to double because of that? Kalbasi et al. found that for every 2 Gy increase in radiation dose, there was a 6% reduction in survival among high risk patients - certainly far from enough to explain the difference observed here.

As for your cynicism...Kishan works for King (who only does external beam), not Demanes. I doubt that he or any of the co-authors who are top doctors at many of the top teaching hospitals in the US (UCLA, Cleveland Clinic, Fox Chase, Mt Sinai, Schiffler) would risk their integrity to form a cabal just to present figures that get them more patients. Demanes wants to retire and doesn't particularly want a lot more patients. Your insinuation is offensive and paranoid.

We are meeting with Kishan and King next week to discuss these options for my husband (dx G9 Less than two weeks ago, bone scan clean and MRI didn't show evidence of metastasis, PNI pos).

Dr. King is currently running a clinical trial involving SBRT (instead of EBRT) along with the brachytherapy boost. Hubby had a long conversation with Kishan on the phone about that yesterday, and we are expecting him to get his first Lupron shot at the appointment. Treatment can't actually begin for two months after that initial shot, so we will have more time to consider options .

I hope this isn't a stupid question given that this is a clinical trial and it's still being researched and studied, but how can we find the information that we would need to make us feel informed between EBRT and SBRT?

Michael_T-

Yes - I wrote the following in my commentary on their earlier study:

Allen said...
Prostate cancer-specific mortality rates were cut in half by combining EBRT with a BT boost. While the combination therapy did not make a statistically significant difference in prostate cancer-specific survival, the study was probably underpowered to detect that with statistical significance. The survival curves between EBRT + BT and the other two therapies did consistently diverge throughout the follow-up period, so the difference might well be statistically significant on a larger sample size or longer follow-up.

/pcnrv.blogspot.com/2016/08/for-very-high-risk-patients-ebrt-bt-is.html

When they enlarged the sample size from 487 to 1,001, the differences became statistically significant.

You're right, Tall Allen. I just re-read the clinical trial parameters, and the trial he's running for SBRT does not include the brachy boost. I misunderstood that (in fact, including the brachy boost would deem us ineligible for the trial).

Studies like the one you posted at the start of this thread had us so sold on the brachy boost, I worry about not including that in the treatment plan. I'm hoping that our meeting with King and Kishan will help clarify some of these choices, but if there's any information (re SBRT vs EBRT+BT boost) you think would be helpful for us to consume prior to the meeting, I'd be grateful for that.

WifeofPie-

Unfortunately, what you're looking for is a randomized trial between an all-SBRT therapy vs a brachy boost therapy, and that does not exist and perhaps never will.

The point that this study is making is that the escalated dose to the prostate is what improves outcomes. Whether that escalated dose is supplied by a brachy boost or an SBRT boost probably doesn't matter much. There may be a difference in toxicity. So far, the toxicity of the all-SBRT approach seems very favorable:

meetinglibrary.asco.org/content/178299-197

The radiation dose to the prostate is very similar (Demanes uses 42.5 Gy, King uses 40 Gy) and the whole-pelvic dose is exactly the same on a bioequivalent basis. I believe the margins are the same as well, as are the doses to organs at risk. The difference between IMRT and SBRT (other than number of treatments) is that SBRT is more precise because it tracks intra-fraction motion (they use the same machines to deliver both).

Interestingly, I'm having coffee with a G9 tomorrow morning that just completed the HDR brachy portion of his Triple Play, since he's interested in how his recovery is comparing to what mine was. He's not really active here at HW so I'm sure he'll appreciate some new info. Thanks TA...

Redwing-
Thanks for editing out your aspersions about those doctors.

The reason why the study you cited is less useful than this multi-institutional analysis is because it's drawn from the National Cancer Database (NCDB), which is good for some things, but not for others. Chief among its drawbacks is the lack of detailed patient information. There is no info on the dose of brachy used. Patients were treated up to 2006 vs. as recently as 2013 in the Kishan study. The NCDB includes community hospitals whereas the Kishan study reflects care at the top treatment centers.

Furthermore, only "overall survival" is given in the NCDB and not "metastasis-free survival" or "prostate cancer-specific survival", as Kishan reports. Based on overall survival, it is not at all in conflict with Kishan, who also found no differences in overall survival (median age for radiation patients was 70 at the start). At 10 years post treatment, brachy boost patients were 42% less likely to have metastases and 44% less likely to die of prostate cancer compared to those who had EBRT only. That's an enormous difference, and is not contradicted by any data that I'm aware of.

TA - thanks for clarifying.

That is a crying shame. As one who has benefited greatly from the treatment I would have hoped to see many more men use it. Interestingly, HDR brachytherapy is increasing for other cancers so more ROs are using it.

One business that has added HDRBT to PCa in the last few years is Cancer Treatment Centers of America. I am not plugging them, just pointing out they are now using it.

Here in Atlanta we have at least three major providers for HDRBT including the Winship Cancer Center at Emory, the Cancer Treatment Center of America and, the center I used, Atlanta Oncology Associates. They have several ROs that perform HDRBT.

On the permanent seeds side of brachytherapy we have the Radiation Center of Georgia that through their founder Dr. Frank Critz started the brachy boost method by combining external beam with seeds about 40 years ago. The trade name is ProstRcision. They are a premier seeds operation and have treated tens of thousands of men from every state and many countries.

So here in Atlanta, brachy boost appears to be alive, well and growing, unlike other areas.