Surgery vs RT mortality rate.

Well, kind of definitive. Radiotherapy has come a long way in just 2 or 3 years. External beam has been perfected as has brachytherapy..not to mention SBRT. Then there is the experience of the practitioners etc. etc. ...and we all know the limitations of observational studies.

randallrrs said...

Finally a definitive study.

Definitive?
No.
Hardly, randallrrs.

First of all, this is not a study. It's a paper published with analysis of the results of other studies that have been previously completed...that's called a "meta-analysis." Not a study. Did you read the paper (or just the brief article about the paper which you linked to)? And, do you understand the major shortcomings which were identified by the authors in the paper?

In my view, the three most important shortcomings were (i) differences in ages of the RP vs RT patients, (ii) age of the original studies and (iii) absence of the isolation of salvage therapies.

(i) It's no myth that radiation is more widely used by older men. Treatment for each and every case should be individualized, and the rigors of surgery can be inappropriately risky for some men as they age and develop other co-morbidities...leading to RT being increasingly common as men age. But the bottom line for the discussion at-hand, in each and every one of the studies analyzed the median age of the RT patients is older than the surgery patients...sometimes by quite a few years. This is going to have an influence on mortality.

(ii) As sheepguy mentioned, RT procedures have improved over time...but so have surgical techniques, so that in of itself is not necessarily significant. However, the RT studies analyzed included brachytherapy, EBRT and IMRT, but most studied the efficacy of EBRT, and today IMRT has largely replaced EBRT, and brachytherapy is on the decline...so certainly the meta-analysis results do not necessarily reflect the latest and greatest.

(iii) Lastly, the results do not include any isolation of salvage therapies. The studies all focused on primary treatments, but men who have failed surgery typically follow-up with SRT, and then systemic therapies, and follow-up for failed RT goes typically directly to a systemic therapy. No accounting for these even though some of the studies included--and others excluded--men with salvage therapy; even though the sole objective of salvage treatments is to extend life. Confounded results.



The most important take-away is the solidification of the understanding that no two cases are the same, and each require individual assessment of the patient's case characteristics before deciding treatment mode, or non-treatment, pros and cons. The analysis did break down the HR for different risk categories, but 80% of the men were in the low-risk category...and today most of those men and many men with intermediate-risk cases would follow an Active Surveillance protocol rather than immediate aggressive treatment.



While this report is NOT "definitive," there is a study in process now that will be quite definitive for men with clinically localized PC: the ProtecT trial. In fact, even the report on this meta-analysis specifically call this out, stating: "Implications for future research assessing the comparative efficacy of surgery and radiotherapy in prostate cancer will largely depend on the results of the upcoming randomized ProtecT trial." Data from ProcecT should be available in 2016, where consenting participants were randomly assigned to AS, RP or RT, with the primary endpoint of PC mortality at a median 10-year follow-up.

This brings me to address sheepguy's questions on hazard ratio. First of all, HR is the standard metric for this type of study and it stands alone. HR is an absolute measure of the difference in hazard rates between two groups, but the details sheepguy asks of--the % mortality for each study from which the HR is generated--are in the report...I'll leave it to you to actually read the report instead of having to "wonder."

Post Edited (JackH) : 12/24/2015 12:35:23 PM (GMT-7)

NP...Merry Christmas anyhow...!!!

Sure, it's interesting. I agree. Reading the report itself is more interesting. But it was your categorization of "definitive" that caught my eye.

I usually don't even read links that people post which don't include any sort of value-added comment, summary or criticisms in their post...but I made an exception here because I knew nothing "definitive" had come out...especially not on the Cancer Network first.

For the reasons JackH mentioned, this tells us nothing useful, and as sheepguy suggested, RT effectiveness is all about reaching adequate biologically effective dose levels. Dose was, and still is sometimes, reduced in older and infirm men in order to keep SEs low. The quality of evidence is low here. As Roach points out, the differences are greatest in the least reliable studies. There are a couple of RCTs that will be more useful than this stuff.

Radical Prostatectomy Versus Radiation and Androgen Deprivation Therapy for Clinically Localized Prostate Cancer: How Good Is the Evidence?

- Allen

Jack, Thanks for the link. I know what HR is..I can spell it. That is truly some wide ranging data with some wide ranging criteria. 1% risk to 1.5% wouldn't seem to worrisome...there are results all over the place..some high risk, some low..some localized only. Doesn't seem like we need to be too worried about HR overall based on this study.

I have seen this before and I am always surprised at it: higher all cause mortality with RT:

Somebody said...
The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54–1.73, p < 0.00001; I2 = 0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76–2.47, p < 0.00001; I2 = 48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.

So OK, this study may not yet tell us what we would like to know about relative cure rates when looking at the most current RT techniques, I get that. But still, whatever was being compared, they(RT) not only had 2 times greater hazard of dying from PC(regardless of risk direction was the same) than with surgery, but 1.6 times HR of dying from any cause. Why would that be?

Well, maybe it has already come to me as I ask the question. The RT guys probably have more co-morbidity, sicker overall, or just older, so naturally they are more likely to end up dead for any and all reasons. Is that it? I think it is.

Good for you, halbert; I think the light is coming on.

You've been in the abyss, perhaps now at your crucible moment, and will emerge to redemption, soon giving solid advice to others with familiar case characteristics.

sheepguy said...
But what would that solid advice be? The course of action he chose ,no doubt . In this particular instance his advice would be "solid" if one was inclined toward surgery, but otherwise there are equally "solid" alternatives.
As for younger men usually ending up with "almost impossible to treat" PCa...where's the science , Halbert?

Well one thing is for sure: the younger when you get it, the longer it has to try and kill you before the old heart attack, stroke, other cancer or jealous husband can. As for " wind up with the fast spreading, nearly impossible to treat variety.", I couldn't say.

sheepguy, I don't know about the science. What I observe is that we've had men under 50 show up here that are diagnosed G8-9 right off the bat. I observe the news not more than a few weeks ago about 'Hot Rod' Williams, former pro basketball player dying of PC at 53, maybe 2 years after he announced he had it.

Admittedly, a small sample, and a non-science and non-peer-reviewed study. However, I've seen others in here comment on it.

As for the rest, Jack, I've always tried to do three things in this space: Share my experience, my history, and my outcome; If there's something I don't 'get', I ask questions; I try to share the facts as I understand them and join the 'slow down' chorus to newcomers. There's also two things I try not to do: I try to stop short of advice giving in the form of "treatment X is the only one for you"; and I try really hard to say what I mean without meanness or sarcasm or hostility.

Not that I do any of it perfectly.

Gee i think you are all getting " it " and as usual in life the ones that think they have "it"... do... but lose more than they have in a lasso of snarkiness. While those who may not have "it" , gain "it" in grace. Me...I have not decided my place...will let others frame mine and happily wander the countryside within....Honk...Honk. Its a new horn my wife gave me for Christmas... black and silver...tho golden in sound. Do you hear it?..Its feint...but not of heart

Yeah, Bozo, but you need know what " it" really "is". No matter what "it" is I doubt it is gained in grace.

It is clear that you HAVE decided YOUR place..what "it" is "is" a different matter.:)