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The Best Therapy for Gleason 10s

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Posted 7/9/2018 12:32 AM (GMT 0)
Gleason 10s (at diagnosis) don't get a lot of attention. They are rare (fortunately), and there is seldom enough of a sample size to deal with it as a separate entity. Even in this subset analysis, there were only 112 of them, and this is the largest analysis of this subgroup ever. Unsurprisingly, they seem to respond best to brachy boost therapy. 5-year adjusted distant metastasis-free survival was 64% for RP, 62% for EBRT, and 87% for BBT:

/pcnrv.blogspot.com/2018/07/the-best-therapy-for-gleason-10s.html
Posted 7/9/2018 2:42 AM (GMT 0)
That's an impressive number for BBT.

Andrew
Posted 7/9/2018 4:18 AM (GMT 0)
I agree - and I think it will get even better if the contemporary PET scans are approved for use in high risk patients. I'd bet that most of the remainder is due to undiscovered micro-metastases.
Posted 7/9/2018 4:33 AM (GMT 0)
I would have thought that micro-mets in the G10 would have been more common.

Still, BBT is a great choice.

Andrew
Posted 7/9/2018 7:11 AM (GMT 0)
i'm a firm believer that BBT is superior to surgery + SRT. in fact I believe many of the recurrences we see here after failed surgery and salvage radiation were avoidable.

ed
Posted 7/9/2018 11:22 AM (GMT 0)
Good results. The numbers should be comforting to those facing that diagnosis. The survival stats are very encouraging.

It's extrapolating a little bit, but the Grade Group 5 classification (G9-10) used to some degree now, could suggest G9 cases might expect similar results from those treatment options. Probably even a little better.
They're lumped together in one Grade Group due to similar risk profiles in other studies.

The follow up period is pretty short for the study, but was there any discussion of side effects from the various options? Five years or so of follow up should be enough time to get a pretty good assessment.
Posted 7/9/2018 4:43 PM (GMT 0)
Redwing-

They already did their analysis on those who were GS9-10, which is referenced in the first line of my write up. This was the GS 10 subgroup. It's confusing (I know it is to me, anyway) but Grade Groups are not a risk stratification scheme - it is merely one of several risk factors. Having done GS 9-10, and now GS 10, I anticipate they will look at the entire high risk group (GS 8-10, or T3/4 or PSA>20).

I think they were lucky to get all these top institutions to contribute data on oncological results, let alone side effects. From what we've seen from other direct comparisons, EBRT alone has the fewest side effects.
Posted 7/9/2018 8:41 PM (GMT 0)
Despite the better outcomes for EBRT+BT there is a shift towards surgery and away fot BBT for high risk cases in US. I found these numbers (don't know how accurate they are).
Between 2000 - 2005, 24% had surgery, 44% had EBRT and 31% had EBRT+BT
Between 2010 - 2013, 53% had surgery, 32% had EBRT and 15% had EBRT+BT
Why is BBT declining?
Posted 7/9/2018 9:12 PM (GMT 0)
Economics. The reimbursement rate is far lower for BT than for IMRT. It has not attracted many new ROs.
Posted 7/10/2018 5:36 AM (GMT 0)

Tall Allen said...
Gleason 10s (at diagnosis) don't get a lot of attention. They are rare (fortunately), and there is seldom enough of a sample size to deal with it as a separate entity. Even in this subset analysis, there were only 112 of them, and this is the largest analysis of this subgroup ever. Unsurprisingly, they seem to respond best to brachy boost therapy. 5-year adjusted distant metastasis-free survival was 64% for RP, 62% for EBRT, and 87% for BBT:

Allen, I looked at the article you mentioned of the results from the GS10 multi-institutional consortium study where they looked at the 112 patients, but didn't find numbers for the 5-year adjusted distant metastasis free survival (DMFS). I'm looking at just the summary, so I'm sure its in the full text (which you have to pay for). In the results, they seemed to emphasize more the 5-year survival vs metastasis free survival:

The propensity score–adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT (BBT) group. The corresponding adjusted 5-year prostate cancer–specific survival rates were 87%, 75%, and 94%, respectively.The EBRT-BT group trended toward superior DMFS when compared with the RP group

So for RP and EBRT-BT (BBT), both overall survival and 5-year prostate cancer-specific survival was close (87% vs 94%), but much poorer for EBRT alone (75%). Is that correct?

Since the 5-year distant metastasis free survival of the BBT vs RP group is much better (per your numbers), but prostate cancer-specific survival is similar, will it take 10 years before we know whether 10-year prostate cancer survival was better for the BBT group. Or can we already assume that since metastasis free survival at 5 years is much better that their prostate cancer-specific survival at 10 years will also be similar?

Was the lack of longer term overall survival why the conclusion was quite open, not recommending one therapy over another? Also are there any implications for SBRT?

Just to be clear, this is the article I'm looking at
/www.redjournal.org/article/S0360-3016(18)30611-4/fulltext
Posted 7/10/2018 6:19 AM (GMT 0)
You are right that I was working off the full text. 5-year PC-specific survival and overall survival are high because almost everyone, even with GS10, survives for at least that long. The 5 year met-free survival curves diverged at 5 years, so it's a pretty safe bet that that trend will continue. It takes awhile for mets to translate into survival.

The timeframe was too short to translate into overall survival differences - it would take 15-20 years to see a difference. That's why met-free survival is used as a surrogate endpoint.

SBRT is another way to boost the prostate dose, but that is still experimental in high risk men.
Posted 7/10/2018 1:57 PM (GMT 0)
25% of the GS10 EBRT patients succumbed to PC after 5 years vs 13% for RP and just 6% for BBT. It's a very small sample, but that would suggest to me that EBRT is significantly worse for GS10 treatment. Do you know from the paper's details if the RP patients received ART (Adjuvant Radiotherapy)?

It's actually counterintuitive to me that such high risk GS10 patients, with very high chance of EPE and local spread should even be treated with RP at all. And I would think that if they had RP, they should probably want ART as well. So it's quite surprising that the 5 year PC survival rate for RP exceeds EBRT alone unless they had ART.
Posted 7/10/2018 3:20 PM (GMT 0)
While not a G10, my otherwise high risk dx prompted three different surgeons to decline to operate. This is in line with the question from Weight Loss.

This continued information regarding the combination of EBRT and BT gives me personal confidence in the effectiveness of my initial treatment. And it continues to dispel the surgery "gold standard" myth especially for high risk.
Posted 7/10/2018 6:24 PM (GMT 0)
As I wrote, post-RP radiation (adjuvant+salvage) was given to 34%, pre-RP systemic therapy (ADT or chemo) was given to 35%.
Posted 7/14/2018 2:50 AM (GMT 0)

Gemlin said...
Despite the better outcomes for EBRT+BT there is a shift towards surgery and away fot BBT for high risk cases in US. I found these numbers (don't know how accurate they are).
Between 2000 - 2005, 24% had surgery, 44% had EBRT and 31% had EBRT+BT
Between 2010 - 2013, 53% had surgery, 32% had EBRT and 15% had EBRT+BT
Why is BBT declining?

Gemlin,
I came across this article, which described a similar pattern, that use of EBRT and BBT are falling relative to RP

/www.renalandurologynews.com/prostate-cancer/radical-prostatectomy-use-for-high-risk-prostate-cancer-rises-sharply/article/672855/

The author suggested:

A number of possible reasons could explain an increase in the use of RP for high-risk localized PCa, the authors noted. Findings from population-based studies have suggested an improved cancer-specific survival benefit with RP compared with radiation. “Although these studies were limited by their retrospective design and unmeasured confounding variables, they were likely influential on patients and physicians,” said Adam Weiner, MD, of Northwestern University in Chicago, the study's primary author.

Among the studies suggesting better cancer-specific survival with RP compared with radiotherapy is a systematic review and meta-analysis of 19 studies by Christopher J.D. Wallis, MD, published in European Urology (2016;70:21-30). The researchers concluded that radiotherapy was associated with a 2-fold increased risk of death compared with RP in adjusted analyses.


The idea that surgery and radiation have the same outcome isn't something which is signed and sealed by medical research. It does, however, seem that research is driving the market towards surgery and away from radiation!
Posted 7/14/2018 4:14 AM (GMT 0)
I don't think it's the flawed research studies that are driving it. The problem with most retrospective studies is that men who get RP are ten years younger than men who get RT. Because virulence increases with age, and older men have an increased risk of death compared to younger men, one can't compare the raw data as they do in the study you cited. I think the problem is that most high risk men never get opinions beyond the first urologist they talk to, and that there are too few practitioners of BBT.
Posted 7/14/2018 12:19 PM (GMT 0)
Weightloss, for the link you posted I looked up the author.

From the "UChicago Medicine", "Find a Physician" info page:

Scott Eggener, MD

Scott Eggener, MD, is an experienced robotic and open surgeon who specializes in the care of patients with prostate, kidney and testicular cancers.

Urologists are surgeons, and surgeons prefer surgery; it's what they do, they believe in it, they're good at it. They're likely to recommend it. It's up to the patient to learn about options, and decide what may actually be best in their particular case.

With any study it's useful to look at who did it - institution, authors, funding, and so on. This will help to identify a study's influencing factors. This is most important with retrospective studies, since they're subject to selection bias by their very nature.
Posted 7/14/2018 12:56 PM (GMT 0)
On Scott Eggner, his primary area of focus now seems to be MRI guided focal laser abalation

/www.jurology.com/article/S0022-5347(16)30917-X/abstract

It's an interesting option for lower risk patients
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