Tall_Allen in reply to Hidden5 years ago

The only reason to change the plan is if distant metastases are discovered. Otherwise, the plan wasn't good enough to begin with. You are right that the treated pelvic LN area is often not wide enough. MSK has been advocating enlarging the treatment area and many ROs are following suit:

pcnrv.blogspot.com/2017/02/...

But none of that changes the fact that one has to radiate what one can't see as well as what can see. For men with low PSA, mets will not be visible with even the best scans. The best scan for finding cancerous LNs would be the Combidex scan, only available at Radboud University in Nijmegen, Holland. But even that one cannot find mets smaller than 2 mm:

pcnrv.blogspot.com/2017/01/...

As you will see if you read the article that Dan cited, it is a dangerous game to wait for the PSA to rise to a level where a PET or MRi can detect it. By that time, the cancer may be systemic and incurable. Certainly, if one has PERSISTENT PSA above 0.2 ng/ml, it makes sense to do a PSMA-based scan to look for distant mets which would obviate the need for SRT, but to wait for the PSA to rise until those mets become detectable is unconscionable.

Hidden in reply to Tall_Allen5 years ago

No comment. Read the references I mentioned.

Reply (0)Report

Tall_Allen in reply to Hidden5 years ago

I have seen them all, thanks. Not one advocates delaying SRT by waiting for PSA to rise so the met will be big enough to be detected. We want to treat while they are small and before they have a chance to spawn.

Reply (3)Report

Hidden in reply to dans_journey5 years ago

There are no data showing that to wait to a PSA of 0.2 has a worst outcome than doing the RT with a PSA <0.2.

In the blog article you mentioned, the ranges the use to compare patients' outcome is <0.2 vs 0.2-0.5 and > 0.5.

In the actual summary of the article by Ahmed Abugharib the reduction in mortality when radiotherapy is done with PSA <0.2 is 4% if compared with the group with a PSA range of 0.2-0.5.

jurology.com/article/S0022-...

We should not forget that this article is a retrospective study and multi institutional. We are basing our discussion in a retrospective study,!!! The scientific value of this type of studies is not the same than a prospective randomized study.

In this study patients were collected since 1986 when equipment and procedures for diagnosis, PSA measures and radiotherapy were complete different than in recent times.

They do not mention the characteristics of the groups ( <0.2, 0.2-05 etc), so we do not know if these groups were comparable in age, Gleasons score, surgical margins, number of positive lymph nodes just to mention a few variables.

You do not have to wait until the PSA is 0.5 or higher since you can get a GA 68 PSMA PET/CT done with a PSA of 0.2 and be sure there are not distant metastasis and if there are local lymph nodes metastasis in the pelvis they are going to be included in the radiation planning.

Tall_Allen in reply to Hidden5 years ago

I agree with you that randomized clinical trials are always preferred, and we have 3 that show that adjuvant radiation is better than a wait and see approach. There are problems with all 3, and we await the outcomes in several years of a few more RCTs that may provide further clarification. Meanwhile, we have to make judgments based on what we have. The Hwang et al. study I cited is the best I've seen so far, and it does indeed confirm that FOR MATCHED PATIENTS treatment before PSA reaches 0.2 has better outcomes.

Reply (0)Report

Hidden in reply to Tall_Allen5 years ago

Again, the study by Hwang is a retrospective study done by reviewing charts from 1986 to 2013.

Even when matching patients this is not a prospective study and to me does not reach the scientific level needed to change medical norms.

Besides it was not done with all patients in possible BCR and it was done with a population of T3N0 patients only, so whatever the findings, they apply only to that population.

Retrospective studies are preliminary studies and they should be confirmed by prospective studies before we start changing the treatment of patients.

The meta analysis of the 3 prospective studies you mentioned did not show a survival advantage according to Hwang et al..

Reply (0)Report

Tall_Allen in reply to Hidden5 years ago

The Hwang study did NOT limit itself to men with T3. All patients had adverse pathology, however.

SWOG S8794 certainly did show a survival advantage to adjuvant RT over a wait-and-see approach. Based on that, the AUA/ASTRO guidelines since the three RCTs on the subject has been to provide adjuvant radiation rather than wait. No one want to do that. So all the retrospective studies since then have been to find out what is the earliest PSA that reliably predicts failure, so that we don't overtreat by treating too soon, but treat soon enough to effect a cure.

While I would like to live in a world where all kinds of money is spent on RCTs and patients have perfect info with which to make a decision, that is not the real world. Researchers have come to a general agreement about what constitutes good evidence. Levels of evidence range from (1) RCTs to (5) professional opinions. On top of that, professional organizations (like AUA, ASTRO, NCCN) grade the evidence on both quantity and quality to arrive at their guidelines and the strength those guidelines have in dictating practice. You would be amazed at the wide range of practices that have never been shown in an RCT.

The Hwang study is notable, not only because of the prestigious institutions (Massachusetts General, Cleveland Clinic, University of Michigan, Duke University, Washington University, Mayo Clinic, University of Chicago, University of Miami, Virginia Commonwealth University, and Thomas Jefferson University) that contributed data, but because of the care they took in analyzing the data. It constitutes level 2a evidence and does indeed inform the practice at top institutions. I know many top ROs, and they all advocate salvage radiation for men with adverse pathology while the PSA is below 0.1 but above 0.03. For men without adverse pathology, they all want to see a convincing pattern of PSA rises.

The gulf between ROs and Uros about when to treat is large. ROs are the ones who actually treat and follow patients who need salvage radiation. They know the heartbreak of treating too late. The Uro's job is pretty much over after surgery, and is mostly limited to treating side effects of surgery. perhaps to justify the surgery gone wrong, they tell patients to wait. I make every effort to get patients talking to ROs rather than Uros as soon as the PSA pattern becomes convincing and over 0.03 ng/ml. They don't always have to treat as low as that (although sometimes they should), but they should be in discussions and considering all the pros and cons.

Reply (1)Report

Emak1 in reply to dans_journey5 years ago

I read a lot of those studies as well. The data is conflicting. I've seen numbers from 70%+ success to don't even try, not worth it. Logically, if your margins are negative, why would it be in the bed vs distant. But there a number of cases where that happened and people were treated. A number of studies are dated, with new equipment and possible ADT combination, not available at the time.

For me it is a coin flip, but one that offers a potential 'curative' road or a long term remission.

The alternative, is your doubling time stays very long and it could buy some more years. But the PCa will remain and could become more aggressive.

The whole thing stinks, esp after 54 months of being in the clear.

Good luck with any choice you make.

Tall_Allen in reply to dans_journey5 years ago

Dan-

I am certainly not against using a PET scan, as you can see in this article:

pcnrv.blogspot.com/2017/12/...

What I am against is deferring therapy to wait for a positive PET scan - I don't think any sane RO would advocate that. In a recent study, 12 year freedom from biochemical failure increased from 43% among men who waited for PSA to rise to 0.2 to 69% among men who were treated before that PSA level was reached;

pcnrv.blogspot.com/2018/01/...

If you want to see a nomogram to help you understand whether SRT is likely to be successful for you, this one is probably the best (be careful about using Wals's book -it is hopelessly out of date):

pcnrv.blogspot.com/2016/08/...

You wrote, "Are there any data yet that show progression-free statistics for those starting SRT at those very early or early levels? Unless I'm missing something, what you presented appears to be just a relative comparison between SRT start times, and doesn't show the overall progression-free success rate of SRT at those various PSA levels." The Abugharib study you cited does just that. They looked at 4 measures of progression: freedom from biochemical recurrence (PSA> 0.2 ng/ml) after SRT, freedom from starting salvage, life-long androgen deprivation therapy (ADT) after SRT, freedom from detectable metastases after SRT, and prostate cancer specific survival. On all measures, those who were treated while their PSA was below 0.2 had MUCH better outcomes (twice as good!) compared to those who weren't treated until PSA was in the 0.2-0.4 range, and four times as good as those treated when PSA exceeded 0.05.

As for being around in 15 years, that is undoubtedly true. And if you have comorbidities that might reduce your life expectancy to only 15 years, that might be an important consideration. Living with the systemic effects of cancer gets progressively harder, as I can assure you from painful experience. You get a window of opportunity in which a cure may be possible.

dans_journey in reply to Tall_Allen5 years ago

Thanks, Allen.

I didn't take it that you were against PET scans altogether, and I had seen that nomogram before. My score would come in 59-125 depending on ADT/no ADT or hi or low radiation dosage, putting my probability of SRT success in the 60%-80% range.

On the Abugharib study, I did see the four measures that they used, but I did see the improvements compared between each PSA range (the twice as effective and the four times as effective), but what I didn't see is the actual results for each of those items.

For example's sake, if current studies show that only 30% of SRT patients are progression free at 6 years after SRT, how does that translate for this study. Let's assume that the 30% number is from those who started SRT with a PSA of 0.5 or more. Does that mean that, according to the Abugharib study, 60% those who start SRT with their PSA between 0.2 and 0.5 will be progression free at 6 years? And 90% of those who start SRT with a PSA under 0.2 will be progression free at 6 years?

I hope that makes sense. I guess what I'm searching for is the baseline starting point. I get that one is 2 times better, and the other is 4 times better, but better than what?

And, yes, I take Walsh with more than a grain of salt. (Although I saw on the JH website that they had a teaser for the 4th edition of the book. I haven't seen it on Amazon yet, but it may be out soon. It will be interesting to see the updates.) As a general rule, I look at the currency of the articles that I read knowing how rapidly things are changing.

Thanks,

—Dan

Reply (0)Report

Tall_Allen in reply to dans_journey5 years ago

I don't understand how the baseline values affect your decision, since you are looking at the relative advantage of one approach over another. But I can oblige: They wrote:

"Increasing detectable pre-SRT PSA (0.01-0.2, 0.2-0.5, >0.5 ng/mL) predicted for worse 10-year biochemical recurrence-free survival (62%, 44%, and 27%, p<0.001), Freedom from Salvage ADT (77%, 66%, and 49%, p<0.001), distant metastasis free survival (86%, 79%, and 66%, p<0.001) and prostate cancer specific survival (93%, 89%, and 80%, p=0.001). On multivariable analysis, ‘early’ SRT (PSA >0.2-0.5 ng/mL) was associated with a 2-fold increase in biochemical failure, use of salvage ADT, and distant metastases compared to ‘very early’ SRT (0.01-0.2 ng/mL)."

Reply (0)Report

dans_journey in reply to Tall_Allen5 years ago

Allen,

Baseline values should be an important part of the discussion and the decision-making process. For argument's sake—and I'm using extreme made up numbers here to prove my point—let's assume a treatment option had a 5% success rate and the study proved a four-fold increase so now you had a 20% success rate. That, to me, is still a sucky (technical term) treatment option that I would have to consider long and hard before electing to subject myself to it, especially if there's risk of having life-long side effects from it that adversely impact my quality of life.

My surgeon was very direct with me prior to the surgery, telling me that there was a 20% chance that the cancer would come back. I landed in that 20%. As a result, I'm more than skittish about pursuing a treatment option that has a 20%, 30%, or 40% chance of putting me right back where I started, only now with life-limiting side effects. And, yes, I understand that the further down the path I go, the larger the risks are and that there are no guarantees. I get it.

I'll say, too, that I don't necessarily subscribe to the theory that we have to do all that we can to prolong our lives at all costs. If the treatment has you curled up in a ball with depression and mood swings; tied to a toilet because you have to have a dozen bowel movements a day; either catheterized or running to the ER because of strictures blocking urinary flow; unable to perform sexually, is that really living? Or is that merely existing? Do you exist for 20 years because the treatments are keeping you alive, or do you LIVE for 10 years doing the things that you enjoy for as long as you can? None of us are getting out of here alive, so if we have some control in how we spend our remaining time, I'm all for it. (If I live another 13 years, I will have out-lived both of my parents and 3 of my 4 grandparents. I'd say that's pretty decent.)

I hope that you now understand and respect that I'm in an extraordinarily difficult position at the moment—like so many of my fellow patients—and all I'm trying to do is 1) come to terms in my own mind with where my personal balance point is between treatment side effects, quantity of life, and quality of life, and, once I have that figured out, 2) determine the best path to get there by assessing the risks as best I can knowing there are no guarantees.

My next project will be to try to find as many studies as I can that report on the long-term side effects of SRT. What percent of men who had an RP and subsequent SRT are affected and to what degree are they affected in the areas of urinary control, bowel control, and sexual function? Is it merely a nuisance, or is it a complete loss of function? If you know of anything out there along those lines, please send it my way.

Thanks again. —Dan

Reply (1)Report

Tall_Allen in reply to dans_journey5 years ago

I misunderstood, I thought you were looking at the relative advantage/disadvantage of treating earlier rather than later. I now understand that you are trying to assess the survival advantage of going for the cure at all, which is a totally different question, and one not at all addressed in that study.

Of course QOL is important, but you seem to be letting your fears run wild and blowing the risk out of proportion. There are definitely side effects to salvage radiation, but compared to the potential side effects of surgery, they are relatively mild and almost always transient. There are also many side effects to living with cancer that grow progressively worse. When people say that most people with prostate cancer die of something else, they are missing the fact that prostate cancer drives lethal comorbidities.

In fact, just today I came across the following study that showed that those who had A/SRT had only a 4% higher overall incontinence rate, and only a 1% higher rate for severe incontinence (>3 pads/24 h) compared to matched RP-only patients. RP + A/SRT was associated with an 18% lower rate of potency compared to RP alone, but that was related to how soon after RP they had the RT. In most studies, bowel function detriments are small and return to baseline within the first year. With your long recovery period after RP, the additional risk should be small.

sciencedirect.com/science/a...

Reply (1)Report

dans_journey in reply to Tall_Allen5 years ago

Thanks for sharing that article, Allen. It's helpful and does put some of those fears to rest. But you know me, I'd like to see more.

I'd love it if researchers shared the distribution of their data when reporting out. I'm going to make up numbers again for illustrative purposes, but let's use the 4% higher incontinence rate as an example. How was that derived? If there were 100 patients in in the survey, did 80 of them report no change in incontinence and 20 of them report a 20% increase in incontinence to get an average 4% increase? If so, it would suck to be in the 20% group (been there, done that, don't want to do it again). But if only 2 of the 100 had a 20% increase in incontinence and all the rest had a 0% to 5% increase, that would tell a completely different story.

So yes, my fears are running a tad rampant at the moment, hence me trying to collect all of this information from reliable, reputable sources to allay those fears. But then I read patient stories like the very first response to this thread—10+ bowel movements a day. It may or may not be a nuisance to him, but I would consider that to be a substantial impact on my quality of life and something that I would want to avoid.

I also recognize that being in these online support forums is a bit of a double-edged sword, too. You can learn much from people like yourself, Raul80, and other patients, but it can also feed your fears when you read of the complications that so many men are dealing with. What we don't know is how many men are outside of the forums who have been successfully treated or who have had minimal lasting side effects. Is it five men outside the forum for every one man in it? Ten to one? Twenty to one? Again, it goes back to that distribution of data.

At this point, I'll continue to research and work on controlling my legitimate fears before my next PSA test and doctor's visit in April. Some days I'll succeed better than others.

—Dan

Reply (0)Report

Tall_Allen in reply to dans_journey5 years ago

They are measuring INCIDENCE rates of incontinence and also degree of incontinence. The 4% higher rate is in the incidence of incontinence of at least 1 pad. The 1% higher rate is in the incidence of incontinence of at least 3 pads. I'm sorry - I've read so many studies that I forget to explain such things.

There is a cognitive bias that we all suffer from, called the "availability heuristic." This means that we overemphasize things like the anecdotes we read on these pages, and undervalue statistics. We overvalue especially those things that have emotional impact - like the suffering of someone we know. Even though I've worked with statistics professionally for over 20 years, I still catch myself doing it. What you have to do is remind yourself that each of the 13,150 men in that study had a story to tell. We also have to acknowledge that, while population probabilities are a best-guess at our outcomes, statistics never predict for individuals.

I've found the best way to control my fear is, paradoxically, to accept it. You seem well on your way to doing that.

Reply (1)Report

Concernedwife24 in reply to dans_journey3 years ago

Thanks dan. I hope to glean from your research. My brain works that way too. Is it worth the side effects to "live longer" if those years are crap!

Reply (0)Report

Hidden in reply to dans_journey5 years ago

Dans:

Your PSA evolution even when it is increasing it has a PSADT around 1 year or more, so you have time to research SRT and make a final decision consulting with your doctors.

I was in the same situation and it took me 1 year to make the decision and I consulted with 3 different doctors in Boston, San Diego and San Francisco. The factor that convinced me to do it was that it can be curative and the only way to know it is to get it done.

When to do it it is the point of discussion.

The article:

Very Early Salvage Radiotherapy Improves Distant

Metastasis-Free Survival

Ahmed Abugharib,* William C. Jackson,* Vasu Tumati, Robert T. Dess, Jae Y. Lee,

Shuang G. Zhao,† Moaaz Soliman, Zachary S. Zumsteg, Rohit Mehra, Felix Y. Feng,‡

Todd M. Morgan,§,k Neil Desai and Daniel E. Sprattk,

it is a retrospective study with 65% of the patients treated before 2005 (1986 to 2005). This was done by chart revue when electronic medical records did not exist. It is not the kind of study (prospective study, ideally randomized) that is used to set norms of treatment in medicine. I believe this is one of the reason that BCR is still define at a PSA of 0.2 or greater.

I wonder if patients with PSA<0.2 may have done better in this study because some of them may have not had a BCR.

I also wonder when those patients with a PSA< 0.2 were treated in the close to 30 years of the study. I think that the patient in the 80's, 90's and earlier 2000's were treated with higher PSA than the more recent patients. The more recent patients (probably treated with lower PSAs) received the benefit of better techniques and equipment.

Best wishes

Raul

dans_journey in reply to Hidden5 years ago

Thanks, Raul. You raise some interesting points that I hadn't thought of before.

I agree that I have time to come to a decision point on this. If the predictive powers of my spiffy little spreadsheet are accurate (they were the last cycle), my next PSA in April should come in around 0.115. We'll see what the real number is in a few weeks...

I chuckled at your comment about BCR being defined at 0.2 ng/ml. I came across a paper where the author had reviewed 145 other studies on BCR and came away with 53 unique definitions of BCR for those who had a prostatectomy. (For those who had radiation, 208 papers showed 99 different definitions of BCR.)

ncbi.nlm.nih.gov/pubmed/172...

That certainly makes it a challenge for someone like me who likes to put things into a spreadsheet and have definitive answers. Nothing in prostate cancer is definitive! Oh well. I've adapted.

Just curious if you have any thoughts on the Freedland study I mentioned earlier? The first link is a summary; the second is the full study.

urology.jhu.edu/newsletter/...

jamanetwork.com/journals/ja...

Thanks again.

—Dan

Reply (0)Report