Another short article on benefits of local therapy for advanced PCa

[snoraste]

Local treatment of metastasis improves oncological outcome in men with prostate cancer undergoing cytoreductive radical prostatectomy (cRP) for metastatic prostate cancer (mPCA)

eusupplements.europeanurolo...

[Dayatatime]

Jeffrey Karnes name is attached to this and he practices what he preaches. I see his name frequently attached to European Urology publications associated with prostate cancer. He will use unconventional treatment and the man saved my life by doing so. Outstanding surgeon and one of the best Urologists a guy can have in his corner.

[Tall_Allen]

As far as I can tell, this was NOT a test of surgical debulking in men with oligometastases. ALL the patients in this study had surgical debulking with RP+ePLND. In the men who had been surgically debulked, they only compared removing mets with surgery or with SBRT. This was a small, non-randomized study in which mets were removed surgically in 9 men, with surgery and EBRT/ADT in 6 men, with SBRT in 11 men, and with EBRT/ADT in 10 men. He found that ONLY surgical removal of oligomets increased survival - radiation of metastases had no effect.

[Dayatatime in reply to Tall_Allen]

I'm not sure what part of that I missed but I'm pretty sure the case shows excellent overall survival benefit at 7 years and suggests a multimodality of treatments should be considered. You probably forgot more about this disease than I will ever know but my opinion is that this type of aggressive therapy is needed. It's gaining momentum and the cutting edge doctors are working on treating to cure as opposed to the 70 year old method of suppressing it. Any research doctor that looks beyond the ideology of palliative treatment needs to be commended. They are working for every man on here and God bless them for pushing the boundaries.

[Tall_Allen in reply to Dayatatime]

No. It definitely did NOT show a 7 year survival benefit. ALL the men in the study survived a median of 7 years which is not surprising.

[snoraste in reply to Tall_Allen]

Allen - sorry for misspelling ..

[Dayatatime in reply to Tall_Allen]

I know your opinion TA, if it's not "proven" or if localized treatment doesn't involve Brachytherapy boost it's not happening. We all have our opinions. It's all about choices and thankfully there are doctors that offer more than "proven" therapies.

[Tall_Allen in reply to Dayatatime]

Everyone is entitled to his own opinion, but facts are indisputable.

[snoraste in reply to Tall_Allen]

Alen,

I think you're reading it incorrectly. 121 patients "underwent cRP" clearly states on first line of the "Materials and Methods" section. It does not seem to be randomized, and I do agree the language could use a little more clarity. Judging by the conclusion of the study, which is an authoritative YES to cRP, and MAYBE to Met directed therapies, I'm guessing the body of the article was a second thought for the author.

[Tall_Allen in reply to snoraste]

I’m not reading it incorrectly. ALL 121 patients underwent cRP. So this study was not designed to compare survival among those who got cRP vs those who didn’t. It finds a benefit IN THOSE MEN to using surgical excision of their metastasis rather than SBRT of their distant Mets.

[snoraste in reply to Tall_Allen]

I see your point. The first part of the conclusion was what caught my eyes - the claim of "excellent long term" outcome for cRP patients. This could be an empty claim, or there maybe some validity to it. This is where we need the full text instead of a poorly drafted executive summary.

[Tall_Allen in reply to snoraste]

That’s what we have randomized trials for. Sadly Mayo is not doing one on this important subject. You’d think they would.

[Dayatatime in reply to Tall_Allen]

Fortunately Mayo does offer debulking or localized therapy with a curative intent when sadly most facilities do not.

[Tall_Allen in reply to Dayatatime]

No one has ever shown a cure is possible. I think they do patients a disservice by overpromising.

[Dayatatime in reply to Tall_Allen]

My experience there I was never promised anything. Actually I was made very aware of the possibilities of failure. With a Stage IV diagnosis what does anyone have to lose? You just might be the lucky one that ends up in a better place. Believe it or not TA some men have put this thing back to bed. As far as cure, with new multimodal approach and aggressive therapies only time will tell. One thing is absolutely certain without trying anything other than standard of care therapies there never will be a cure.

[Tall_Allen in reply to Dayatatime]

I have no doubt that some men have achieved remission of their cancer. The question that no one (including Karnes) knows the answer to is whether it has increased survival, let alone cure. The recent STAMPEDE trial found that there may be a benefit to prostate-directed radiation in oligometastatic men. This small study found no benefit to radiation of oligometastases. There are larger trials in the works.

The way standard of care becomes standard of care is through clinical trials. There are some great clinical trials in process now of both debulking and metastasis-directed therapy. Sadly, Mayo has not announced any.

I continue to support treatment of metastases when it is safe to do so - why not? Debulking is another matter because the treatments are toxic. I don't think it should be done outside of clinical trials. In either case, systemic therapy should not be delayed after metastases are discovered.

[Break60 in reply to Tall_Allen]

TA

You say you continue to support tx of mets when it’s safe. Yet you say there’s no proof that it extends life. Do I interpret you correctly ?

Bob

[Tall_Allen in reply to Break60]

Yes, Bob. Like dietary changes and supplements, no one knows if there is a benefit to most of them, but why not if there is no indication that it is unsafe. But safety has to come first when there is doubtful benefit. In a recent study of SBRT radiation to oligometastases, 30% of the people getting SBRT suffered grade 3 (serious) side effects, and 3 of the 67 or so people died as a direct result of the radiation. Sometimes a "folie a deux" effect occurs when the patient, wanting to be helped, and the RO, wanting to be helpful, push the bounds of where radiation should be given, especially in the thorax.

[Break60 in reply to Tall_Allen]

Well I had sbrt to a met in femur in 2017 with no recurrence and now have one met in scapula and one in rib . My RO is now examining the CD from the PSMA ga68 scan to figure out if sbrt can be safely administered. He used the same machine (trubeam )he uses for IMRT. He also has a cyber knife machine which is reserved for other types of cancer as I understand it. Meanwhile I went back on xgeva and trelstar to see if It works or if I need to start Zytiga. I know you’re a proponent of using second line adt early right?

Bob

[Tall_Allen in reply to Break60]

Yes, a new analysis of STAMPEDE showed that Zytiga works equally well with few mets as with multiple mets.

[sammamish in reply to Tall_Allen]

Hi Tall, just reading this now. Belated question for you. What is the study you are referring to here so I may read it? I am toying with the idea of gamma knife for a few hard to excise para aortic PSMA positive lymphs. Actually, not super inclined to do since I have germ line ATM gene, but am considering.

thanks.

Samm

[Tall_Allen in reply to sammamish]

I'm not sure what you're asking about - STAMPEDE? With an ATM gene, I understand your hesitancy to have radiation so close to the vena cava and aorta. Have you talked to an RO about it?

[Tall_Allen in reply to snoraste]

I would also offer that in 1999 (see below), Johns Hopkins found that from the time of PSA recurrence to the time the first metastases were discovered on a bone scan/CT was a median of 8 years, and 5 years after that was the median survival. Because Mayo detected mets earlier using C-11 Choline PET/CT, they created a "lead-time bias" so that 7 years median survival is reasonable without any debulking. Plus, 1999 was before docetaxel, Zytiga, Xtandi, Erleada, Jevtana, Xofigo, or Provenge which we know adds to survival. Without a control group for comparison, he has no basis for making a claim that 7 years of survival is "excellent."

jamanetwork.com/journals/ja...

[snoraste in reply to Tall_Allen]

I do agree that we need a context for the term "excellent". Mind you that it is a relatively recent article, so the authors should be (theoretically) very familiar with recent survival studies and yet they are making this claim. I also don't understand the "lead time" argument. Nowhere in the article I'm seeing a reference whether the population has a recurrence, or just newly diagnosed. I agree that RCTs are the benchmark, all else equal (I think all rational people agree with that). But as we all know, all else is not always equal, and they too can suffer from "bias". What is lacking in medical publications is a rigorous peer review. But again, who makes money doing that.

[Tall_Allen in reply to snoraste]

The lead time argument means that because the metastases were diagnosed sooner (because they used superior imaging), it APPEARS that they survived longer than the median of 5 years. In fact, they may have survived with metastases just as long as in the Johns Hopkins study.

Perhaps an analogy will help. Imagine a train that crashes in D.C. (God forbid) and that began in Boston and stopped in NY on the way. Let's say that Boston to NY takes one hour, and NY to DC takes one hour. It appears that Boston passengers survived twice as long compared to NY passengers. One might conclude that living in Boston is 2X better for survival than living in NY. That is called "lead time bias."

The population is newly diagnosed with metastases. It is apt to compare them to the Johns Hopkins study because everyone in the JH study also had a prostatectomy just as at Mayo. At JH, some of the recurrent men would have had distant mets discovered during the 8-year period if they had had a C-11 PET scan. There is no reason to believe that the time that they survived after distant metastases was any different.

[snoraste in reply to Tall_Allen]

I get your point Allen. That's why a context for their claim is crucial in understanding their statement. Perhaps I send them an email!

[Dayatatime in reply to Tall_Allen]

For one thing it's not just "he" because there are a total of 9 doctors attached to that article. You can put down The Mayo Clinic and Karnes all you want but the fact is they are an exceptional facility that will push every protocol known to hopefully achieve a better outcome for the patient. I can speak from experience because they did exactly that for me. Have you ever been there?? Have you ever been told you had Stage IV metastatic cancer and told you'd possibly be dead in 5 years?? Then finally find a doctor that is willing to give you a chance when no others will and possibly pull it off. That my friend is Dr. Jeffrey Karnes.

[Tall_Allen in reply to Dayatatime]

So you are happy to get a promise, whether there is evidence or not? I think the better doctor is one who is honest about the odds, as difficult as it may be for him to say, and as difficult as it may be for us to hear. Both of my parents were told they had metastatic cancer and would be dead in months, so yes I know the feeling of grasping at straws. Fortunately, they had doctors who were tops in their field and were honest about their odds and what they could and couldn't do.

[Dayatatime in reply to Tall_Allen]

Karnes did not promise me anything. He was completely up front with everything and his initial goal was not curative it was to add years to my life. It just happened that things went better than planned and I came out of it the best anyone could ask for. He has not once said I am cured because the fact is it will be several years before that determination can be made. In fact when I bring up the possibility he just smiles and says we will talk in 10 years. I understand that but I am elated that he, when no one else would, got me to a place of possibility.

Great doctors push to figure out if they can do something others cannot incorporating new theories as well as learning from the old. They are completely up front with you about the odds but are thinking of how to get around them. Think of the men who could have possibly been saved in just the last 20 years if debulking was done with only limited mets in nodes alone. I shudder to think about the men closed back up simply because a positive node was found. New aggressive multimodal therapies are shedding some badly needed light that curative is now a reality. Dr's such as Karnes are the ones making it happen because he does not stop at outside the prostate your limited.

There are no guarantees with any cancer. Even treatable cancer can take a turn for the worse. Duke University cured a case of the most deadly Glioblastoma when the patient should have been dead in 2 weeks. It was a hail mary move that paid off. Not a proven treatment and didn't work in others when tried afterwards but it did save that young woman's life. So yes in my opinion sometimes you have to get past the proven and take chances while knowing all possibilities.

[snoraste in reply to Dayatatime]

I do agree with parts of what Dayatatime said here. I, too, had an RP a few months ago. It was at the recommendation of MSK. Since there is no level-1 evidence, it's a personal choice based on your overall condition, and balancing the pros and cons. I am not expecting a cure. But I'm positive that my internal organs near the prostate bed will thank me for it later. The question is: if you are stage4 and can tolerate the side effects, why not?

[Tall_Allen in reply to snoraste]

I agree completely. It boils down to the patient taking a leap of faith.

[Tall_Allen in reply to Dayatatime]

You have no idea if it improved your survival - unless you have a crystal ball that can show you what your outcomes would have been if you had chosen another course of action. Doctors make all kinds of predictions, both optimistic and pessimistic. The fact remains that the best they can do is quote odds based on the population statistics. Without those statistics, it's just a guess.

[Dayatatime in reply to Tall_Allen]

Yup. Actually I could've did nothing and I'm sure the Lupron would have worked for a few years anyway and oh how I love living with the side effects of that. Just a superb quality of life at 49 years old. I thank God every day for helping to guide me through this mine field of a disease. Every doctor I have spoke to from the beginning of this and current are shocked at what I accomplished and the work of Karnes. They now commend me for taking things into my own hands. Several in the beginning never thought it possible. Nope, no crystal ball but I don't need one because I know where I was and I know what got me here. It sure as hell wasn't the 5 other doctors who told me it couldn't be done.

[Tall_Allen in reply to Dayatatime]

You aren't taking Lupron?

[Dayatatime in reply to Tall_Allen]

Last shot was February and effects are slowly but surely going away. Growing hair again in all the right places and even need deoderant. Can actually wear a long sleeve shirt without feeling like I'm melting in it.