Men with biochemically recurrent prostate cancer, who defer hormone therapy until metastasis have overall survival that is quite long and the early initiation of continuous androgen deprivation therapy for biochemical relapse, may not meaningfully improve overall survival. Adequately designed prospectively randomized studies in patients with BCR testing the role of early vs deferred ADT remain critical to inform treatment decisions in this population and enhance patients’ and physicians’ understanding of the clinical significance of the nmCRPC pivotal studies.
These data provide context for patients with BCR and providers on whether to undergo ADT for years despite unproven benefit and quality of life impact. New imaging may help or further add to the controversy, since BCR patients may have metastases on newer imaging. Until definitive data are available, men with BCR should be counselled regarding the lack of data to support ADT benefit in nonmetastatic BCR.
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maley2711
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so, synopsized, the study is saying if your PSA goes up 2 points, thus making it a recurrence, then it doesn't matter whether you use ADT or not until full metastasis (however that is defined), your overall survival will be the same. Right?
I don't think your conclusion is one that this study makes? They do say that there is an average survival of > 10 years for that group who delayed ADT until metastasis detection. But always remember , average is not a prediction for any one man...could be 6 years for one man, and 20 years for another...unfortunately, we do not yet have a proven way to better determine one man's risk.
Also, see TA's reply in disagreement with the value of this study..though I don't necessarily agree with his disagreement.....maybe I'm just not properly equipped to determine value of studies? I acknowledge I have no training for doing so.
Another worthless retrospective study. You can easily see the selection bias- the single biggest factor predicting metastasis-free survival was whether patients were treated at Johns Hopkins (5 times as likely to be met-free) and African-Americans had twice the rate of metastases vs Caucasians - In fact, African-Americans were twice as prevalent in the Walter Reed cohort.
Three randomized trials have now proven the value of short-term early intervention with advanced hormone therapy (Zytiga, Xtandi, and Erleada). I expect that PSMA PET scans will virtually eliminate the category of non-metastatic castration-resistant PCa.
I am trying to understand your last sentence. Do you mean that we will find that by the time the cancer becomes castrate resistant, that in nearly all cases there are mets. Mets that previously we were unable to detect but can with PSMA-PET?
I'll communicate your conclusion to them? Selection bias because patients were treated at JH?? Many studies look at patients from one or a limited number of institutions? I think you've favorably cited a number of them? Do you believe these credentialed folks aren't aware of the randomized trials you mention??
You advise that the minute a BCR is detected, every man begin this high burden combo drug treatment ?
In any event, Ididn't read that there was a claim that delaying treatment was equivalent or better than earlier treatment.....just that those delaying treatment still had overall > 10 yr survival...and an implied delay in treatment SEs.
Granted , Walsh's 2018 version is now 4 years old, but still relatively recent, and he was not/has not been an advocate for immediate treatment after BCR.
" This underscores the need to reevaluate when to start primary ADT in this patient population. " I am seeing many Docs concerned about QOL impacts of treatments.... urging a faster development of better markers to further categorize men as to risk ...so as to expedite certain heavy-duty treatments for certain men and de-escalate for other men.
Selection bias because it is a retrospective study. They are well aware that it is a limitation of their study. The only way to avoid it is to do a prospective randomized study. The only problem is when patients like you who are ignorant of research methods draw unwarranted conclusions.
I did not say that every man with a BCR has to have therapy. Please don't put your words in my mouth.
Not trying to do that....simply trying understand your meaning. Are you saying that their review didn't find a group of non-metastatic men who experienced BCR and had > 10year survival, after BCR, until metastasis finally detected by conventional scanning? they also state " Adequately designed prospectively randomized studies in patients with BCR testing the role of early vs deferred ADT remain critical to inform treatment decisions in this population " You say that these MDs seem to be unaware of studies that answer the question they are posing?
I already told you what is wrong with it. No, I'm saying that patients like you go around quoting meaningless studies because you do not understand research methods and how to interpret such studies. If you understood that, you wouldn't have posted it - twice no less -- as if it were a landmark study!Those MDs know such studies should not be used for the purposes for which you are trying to use them. They do it to get published, which is critical in academia. They would be horrified that you are trying to use it for therapeutic decision making.
NOT trying to use for decision making...putting words in my mouth? I did err re MFS...it is from time of RP. The NCCN guidelines discuss need for further research re benefit of immediate ADT after recurrence..though on other hand seem to suggest salvage RT +/- ADT for M0? Question that came to my mind on 2nd read was,,,,,did they cherry pick the M0 men who delayed ADT after recurrence. I'm under the impression that most M0 recurrent men after RP have RT +/- ADT. Apparently these men studied were a VERY small subset of men.... "All men who had a radical prostatectomy from 1983 to 2014 and developed BCR with a PSA doubling time of <10 months were included, consistent with the eligibility criteria of the nmCRPC trials. Those who were started on ADT prior to metastatic disease were excluded which includes patients who received adjuvant or salvage radiotherapy with ADT. "
Editorial Comment ( 2nd link )...
" The question of how best to manage BCR remains controversial. Marshall et al contribute to this debate by examining outcomes for patients with high risk BCR (defined as PSA doubling time <10 months after radical prostatectomy) from 2 large institutions and who did not receive ADT until developing metastasis. They contrast outcomes with data from phase III trials of androgen receptor-targeted therapy in nonmetastatic castration resistant PCa (nmCRPC). Although different populations, outcomes of high-risk BCR patients who delayed treatment compared favorably to nmCRPC on intensified therapy; median metastasis-free 192 months and OS 204 months from time of local treatment. These data provide context for patients with BCR and providers on whether to undergo ADT for years despite unproven benefit and quality of life impact. New imaging may help or further add to the controversy, since BCR patients may have metastases on newer imaging. Until definitive data are available, men with BCR should be counselled regarding the lack of data to support ADT benefit in nonmetastatic BCR. "
Do you disagree with the editorial comment? Unqualified MDs? I don't think anyone is questioning that 2nd line treatment is beneficial for failed initial salvage or adjuvant ADT when men become castrate resistant?
Certainly, PSMA PET will reduce the number of men who appear non-metastatic after PSA recurrence with older scan tech.
Meanwhile , I see that my PSMA PET results are available, and I'm terrified to look!!
Your sincere dummy member of the PCa club.....Dale
"You advise that the minute a BCR is detected, every man begin this high burden combo drug treatment ? {I, of course, said nothing of the kind]In any event, I didn't read that there was a claim that delaying treatment was equivalent or better than earlier treatment.....just that those delaying treatment still had overall > 10 yr survival...and an implied delay in treatment SEs."
If that's not trying to make a treatment decision based on a meaningless study, what is?
In fact, you still seem to be looking for meaningful direction from a meaningless paper. Give it up and move on, Dale!
Yes, I disagree that it provides anything useful. You can't make a silk purse out of a sow's ear. This is especially true when the study is only of 2 institutions and the patient base is so glaringly different between them. Clear selection bias ruins this study.
If you want less chance of selection bias, you have to include many more institutions and the patient characteristics have to be matched. This is what was done in the following:
As you see, Van den Broeck studied 20,406 patients at 77 hospitals, and his results were later validated separately by Tilki (1125 patients), Preisser (2473 patients) and Pompe (1821 patients). None of those are prospective trials, but, lacking that, they are the most reliable data we have.
That is a good study. and finds results that make sense I think. The multivariate analysis of study I lnked was in line with some of Van den Broeck 's results...... I think the JH/WR study did not in any way conclude that all men should just delay any treatment after BCR.....you are reading my mind incorrectly, just as you said I did with respect to interpreting what you said. To me, the JH study simply pointed out that just the fact of a BCR is no reason to demand or feel the need for immediate salvage...and they were acknowledging the QOL impact that ADT often/always brings with it. Just the way I read it. Anyway, I gave none of my personal opinion in the post...anyone who read it could form their opinion. I don't agree with your that these MDs are just a group of hacks.....knowingly publishing meaningless garbage to satisfy some academic demands, but at least I'll acknowledge that I could be wrong....don't expect you would.
The JW study is garbage and should not be used to draw any conclusions, I showed you the reasons, but you seem locked into it. That is your choice. Just don't expect me not to call the garbage you posted as garbage.
So basically, non-metastatic castration resistant PCa doesn't really exist. It's there, just not showing up. Is that a fair statement? I'm new to the term nmcrPCa.
I doubt that there is really such a thing as CRPC without any metastases, The term "metastatic" when used in staging means that it has been detected on a bone scan/CT. It is denoted by M1. Some think there should be a substage for metastases detected by a PSMA PET scan only, like PSMA M1. But even that has a size limitation - metastases smaller than about 5mm are undetectable by any kind of imaging we have now.
NMCR apparently refers to men who agreed to ADT after PSA recurrence post initial treatment(surgery or radiation), but for some reason PSA rises without metastatic findings...the usual reason for PSA recurrence is missed organ-confined PCa .....or metastasis to reginal LNs, or distant organ or skeletal PCa metastasis. As TA states, advanced newer imaging should reduce the number of those men with undetected metastasis...but not to zero! A big problem is that almost all treatment studies that have guided treatment guidelines have been based on results from older imaging methods.
Yes, for sure !! Benign prostate tissue that is not destroyed by radiation, and same for tissue left behind by surgery.though much rarer. Also, either treatment can be unsuccesful in killing/removal of all local pCa tissue..then patient proceeds to slvage treatment....typically radiation +/- ADT after "failed" surgery, andseveal options after initial "failed " radiation. also, there may be metastasis that still remains in lymph nodes that was not dealt with by initial treatment.....salvage treatment for that situation may be successful. With radiation, apparently it can take up to 2 years until PSA stabilizes at a nadir..hopefully very low nadir.....that's one thing some men like about surgery, much shorter time until probable success/failure is known....though recurrences can happen even 20 years later!!helpful?
You remind me of the "intelligent" guys in the alcohol treatment program many years ago. Most of them failed treatment. It was confirmed by the dr.'s that the smartest amongst us always can outsmart themselves into failure. If you want to avoid recommended treatment or only do treatment you are comfortable with I'm sure you can find the information (unreliable as it may be) to match your rationalizations. Not sure why you look here for more rationalization in the guise of learning from us.
I assume your reply was directed towards me? If so, why do you say " If you want to avoid recommended treatment " ? what did I say that led you to such a conclusion?? I certainly do not " look here for more rationalization in the guise of learning from us.
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