HealingWell
Search Close Search
☰

AS success does not equal long term G6 indolence

Support Forums
>
Prostate Cancer
✚ New Topic ✚ Reply
12
❬ ❬ Previous Thread |Next Thread ❭ ❭
Posted 4/15/2016 4:06 PM (GMT 0)
Hi all,

I have reposted this reply to a different thread as a separate topic, primarily because it detracts from the original posters intent. I invite ASAdvocate and JackH to repost their replies if they wish.


I don't post often but I do read the forum frequently. I first want to say that I am apparently an AS success story (time will tell, but I am very optimistic). I completely agree that AS should be strongly considered for any man who qualifies.

I do think that sometimes the success of AS studies is used to infer that low grade PC is indolent, and does not progress or metastasize, and perhaps should not be considered PC (G6).
I do not think the studies support that philosophy.

In the most often used Klotz Sunnybrook study, by year 10 almost 41% of men initially meeting criteria had met clinical indicators of progression to the point of intervention, and by year 15 that had gone up to 45%.

The fact that these progressions were marked at 5 year intervals
argues against initial sampling error.

So, while the overall survival rate of this study is excellent, it includes a large percentage of men who had to be treated to maintain that success.

Another long term (30 years) study (referenced by Klotz) by M Popiolek suggest that
overall PC mortality (in untreated low risk patients) is 11% at 15 years and 28% at 20 years. That is far from zero.

I know 15 or 20 years is a long time, and not that important if a man is in poor health or later in years. But, in a man in his 40's or 50's, the odds are that low grade PC will become an issue to be dealt with.

I don't mean to step on toes, but there is always more in the details.
Diagnosed in August 2010 (age 46)
AS for 3.5 years
Biopsy October 2013 found more G6
re-read by Bostwick 3+4=g7
Davinci LRP 1/2/14
post op pathology organ confined G6, all margins negative,
30% volume, both sides involved (much more than clinically indicated)
climacturia
No ED.
PSA zero 4/14
PSA<.01 7/14, Testosterone 178 (hmm?)
10/24 <.01, T. 147
Posted 4/15/2016 4:09 PM (GMT 0)
from ASAdvocate on different thread.
Dan, the history of Johns Hopkins AS program has far better results than that.

https://prostatecancerinfolink.net/2015/09/01/new-data-from-johns-hopkins-on-outcomes-after-active-surveillance/
DOB: May 1944
In AS program at Johns Hopkins
Five biopsies from 2010 to 2014. The third and fourth biopsies were positive with one core and three cores <5% and G 3+3. Fifth biopsy was negative.
OncotypeDX: 86 percent chance of PCa remaining indolent
August 2015: tests are stable; no MRI or biopsy this year for my AS program
March 2016 PHI = 28; a good result for AS
Back to Top



ASAdvocate,
I see that you are in the AS program at JH. Good for you. That is perhaps the best designed and well run AS program in the world. It is worth noting that the criteria for the JH program is also the most stringent.
Even with strict requirement, the rate of upgrade is 26% by 10 years and 31% by 15 years. Also, by 10 years, almost 50% had met certain clinical triggers for intervention (not necessarily an upgrade). That number also increased at 15 years.

I hope that my point was clear. I am also and advocate of AS for men who qualify. But these studies are designed not only to identify indolent (or very slow) cancers, but to also catch cancers that are progressing, before the opportunity to cure is missed. And they do find many of the latter. The success of those (treated) is factored into the total, thus skewing the numbers toward very low mets and mortality rates (which is the aim).
We do not know what the numbers would be if those men had not been treated.

Be well.
Diagnosed in August 2010 (age 46)
AS for 3.5 years
Biopsy October 2013 found more G6
re-read by Bostwick 3+4=g7
Davinci LRP 1/2/14
post op pathology organ confined G6, all margins negative,
30% volume, both sides involved (much more than clinically indicated)
No ED.
PSA zero 4/14
PSA<.01 7/14, Testosterone 178 (hmm?)
10/24 <.01, T. 147
PSA's <.01, still very low T.

Post Edited (Dan0) : 4/15/2016 10:13:02 AM (GMT-6)

Posted 4/15/2016 4:13 PM (GMT 0)
Couldn't agree with you more DanO..
Posted 4/15/2016 4:53 PM (GMT 0)
This is really quite straight forward. While it is correct that Gleason 3+3 does not metastasize, there is nothing from preventing other cells with Gleason pattern 4 from developing elsewhere in the prostate in the future. This is why we have AS FUNDAMENTAL #4, that men on AS need ongoing monitoring...to see if more advanced disease develops in the future or was missed in earlier biopsies.

As your thread title implies, some men can stay on AS for the rest of their lives, but not all. AS is not a promise of no treatment ever needed; rather, it is a deferral until treatment is needed (if ever).
Posted 4/15/2016 4:59 PM (GMT 0)
"While it is correct that Gleason 3+3 does not metastasize...."

JackH, with respect, I do not believe that has been unequivocally proven. But I completely agree that men on AS need ongoing monitoring.

Be Well.
Posted 4/15/2016 5:10 PM (GMT 0)
Dan0, you are correct, and thanks for holding me accountable. One cannot prove a negative, and as a daily practitioner of statistics I should know this.

Please allow me to re-state (in this case, I'll just reuse Dr. Sperling's words: There is increasing evidence that G6 does not increase to G7, or eventually metastasize.
Posted 4/16/2016 1:45 AM (GMT 0)
Right on Dano…you pretty savvy for a young guy...
Posted 4/16/2016 2:43 AM (GMT 0)
I think we are missing the most important point of AS. We know that a % of patients will progress, wether that is the often quoted 30% or 45% doesn't matter. The true purpose of AS is to identify those who will progress and treat then, and not treat the 55% or 70% that will not progress,
Treatment does not mean cure 100% wether treated immediately or delayed. There will always be some failures. Data shows that there is a similar % of failures for delayed treatment vs immediate treatment. The upside is that in AS a majority of men will never be treated, never progress and never suffer any side effects.
Posted 4/16/2016 4:38 AM (GMT 0)

John T said...
I think we are missing the most important point of AS. We know that a % of patients will progress, wether that is the often quoted 30% or 45% doesn't matter. The true purpose of AS is to identify those who will progress and treat then, and not treat the 55% or 70% that will not progress,
Treatment does not mean cure 100% wether treated immediately or delayed. There will always be some failures. Data shows that there is a similar % of failures for delayed treatment vs immediate treatment. The upside is that in AS a majority of men will never be treated, never progress and never suffer any side effects.

What % of G6 men progress even if treated? And G3+4 treated men?

It is clearly not zero.

Next question in reference to this: "Another long term (30 years) study (referenced by Klotz) by M Popiolek suggest that
overall PC mortality (in untreated low risk patients) is 11% at 15 years and 28% at 20 years. That is far from zero.".

This seems high to me, but maybe I am misinformed. Anyone? If that is true, then they do as bad or worse than high risk men treated mostly with surgery only, according to several studies.
www.ncbi.nlm.nih.gov/pubmed?term=%28%28%28%28%28Pokala%2C%20Naveen[Author]%29%20AND%20Radical%29%20AND%20Prostatectomy%29%20AND%20High%29%20AND%20Risk%29%20AND%20survival

Somebody said...
Cancer-specific survival was 96.4, 89.5, 82.0, 72.9, and 68.8 % for 5, 10, 15, 20, and 25 years, respectively.



But, I guess the only question that counts: what % of untreated AS men, counting the ones who later get treatment when shown to be progressing, survive 20 years or whatever # is preferred? And how does this compare to men treated upon diagnosis? Because if that PC survival # is similar, then even if 100% end up being treated 5 or 10 years later, that is still 5 or 10 years with no SEs from treatment. But in reality the majority will never be treated.
Posted 4/16/2016 11:26 AM (GMT 0)
Dan0, while I thank you for wishing me well on the other thread, I have to disagree with your viewpoint here.

This conflict in perspectives may be due to the fact that we were 22 years apart at time of diagnosis, and apparently our expectations of AS were shaped by that. You were almost 20 years too young for the formal AS programs when you decided to give it a try. I salute your trying and your success at having several more untreated years. But, the odds were never that favorable for a 46 year old to expect not to be treated at some point.

In my study cohort, where the registration age is about 67, the retention rate is 66 percent. Clearly, the odds favor older men as the best candidates for staying in AS.

Regarding G6 becoming G7, I have read a article by Dr. Carter, who founded the AS Program at JH, stating that he has only confirmed two cases of a G6 cancer genetically morphing into G7. That's less than one in a thousand.

There are now additional tools like the OncotypeDX and Prolaris tests, which analyze the genomics of prostate cancer cells, in order to predict which patients are best suited for long term AS.

Your point is basically correct that some men doing AS will later have unfavorable biopsies, and need treatment. But, that does not invalidate the fact that many men, including the majority in my study group, will not experience that progression.
Posted 4/16/2016 2:07 PM (GMT 0)
My point was never to question the validity of AS programs. And I think the new tools available will make those programs even more successful.I had just grown weary of seeing statements on this forum that diminish the seriousness of low grade PC. I think it would behoove us all to avoid absolutes in regard to G6 or G7 (3+4).Encouragement is always a good thing, but we should be careful with our words less we convey a false sense of security.

Be Well
Posted 4/16/2016 2:46 PM (GMT 0)
Dan0, being a man of science, I agree that the data should--and does--speak for itself.

And patient education about the data and what they mean in context is improving, too. The shift away from one-size-fits all rushed (over-)treatment is one of the favorable outcomes, thankfully. I encourage men to make a data-driven decision versus an emotion-driven decision.
Posted 4/16/2016 3:09 PM (GMT 0)
Dan, your point is well taken. I've seen it also, where there are absolute statements made here that should not be made. Not every G6 stays G6 forever--and whether G6 turns into G7, or whether G7 springs up on it's own is one for the expert pathologists to define. AS is a tool we have to detect that move from G6 to G7 (or higher).

We need to be cautious and be careful we don't tell the vulnerable what they 'should' do beyond suggesting questions to ask and presenting factual information. Telling someone what treatment they should pursue--whether it's because we had a good experience with that treatment or whether it's because it's the treatment we wish we had pursued--is going too far.
Posted 4/16/2016 4:14 PM (GMT 0)
As a "youngish" AS guy... the point for me isn't whether I will need treatment in 5 years, or 10 years, or 20 years, it's that I get all of those years with ZERO SEs with practically no risk (in my case) of an adverse outcome because of my choice. I get that there is some risk, but it's a risk I gladly take.
Posted 4/16/2016 4:25 PM (GMT 0)
Billy Bob,
I read all of Klotz's reports years ago, so I'm quoting from memory. As I recall there was a 5% difference in low risk cases that were not treated compared to those that were treated at 20 years. There was no difference in immediate compared to deferred treatment.The progression rate as about 30-35% and the vast majority of progressions occurred within 3 years.
There was a 1.6% death rate for low risk patients in 3 years, whether treated or not. This was due to variants that appeared to be low risk, but obviously were something more serious.
The basic point that Klotz was making is that at 20 years "watchful waiting" meaning doing nothing had a 5% greater risk than an AS program in which progression was treated. There was also a 1.6% risk of death regardless of any choices made.
Posted 4/17/2016 2:08 PM (GMT 0)
"The progression rate as about 30-35% and the vast majority of progressions occurred within 3 years."

JohnT, with respect. The data show that at 5 years, 24.5% of men had been treated, at 10 years 37.5%, and at 15 years 45%. I do not agree that 24.5 % equals a "vast majority". The progression, after an initial spike which could be attributed to sampling error, seems to be consistent throughout the timeline of the study until year 10 and then increases slightly.
It is also documented in that study that the cohort includes many intermediate risk men (70 years old, G3+4, PSA 15 or less) with life expectancy of less than 10 years, which certainly would allow for an initial spike in progression rates. And that these men would die of something other than PC skews the PC mortality rate to the low end because men who might have metastasized and succumbed after 10 years were no longer alive to be included in the study. In all, only 206 (of 993) were observed for at least 10 years and only 50 for 15 years.


Also, the study started in 1995 and the latest data was locked for review in 2013 (18 years), so your comment concerning Klotz' basic point seems unsupported by his own documented parameters.The WW study from Popiolek, referenced by Klotz, suggest the mortality rate in untreated low risk patients is 28% at 20 years. Can you clarify your comment please?
Posted 4/17/2016 3:15 PM (GMT 0)
JohnT may or may not respond later, but I can help with some of your questions, Dan0.

It appears you've misinterpreted one of his comments, and perhaps it could have been stated more clearly. (I'm familiar with the data JohnT referenced, too, and can clarify.)

First of all, please do note that there have been various studies of progression rates, and none of them are the same to the first decimal point of precision...but they do all follow the same general trends.

Moreover, to your comment, a consistent observation amongst the studies is that for the sub-set of men who do progress while on AS, the most significant number moves to active treatment within the first several years. Your case is an example of this. After that, the rate of conversion from AS to active treatment slows down. The data you provided illustrates this point in this way: After 5 years, 24.5555% progressed. After double that time, less than double the number of men had progressed; only 37.5555%. After 15 years, the slope of the curve flattened even more.

Hope this helps clarify for all.
Posted 4/17/2016 3:40 PM (GMT 0)
Dan0, I have been on AS for seven years, which is twice as long as your attempt at age 46. I now have to question why you are so adamant about arguing that there is a high level of progression. That is surely not the case for my study cohort, which began in 1994.

To me, the data that you cite is not adding anything that I and others were not long aware of, and have chosen to disregard in favor of data more specific to our pathologies and mindsets.

There are several predictive tests and tools that did not exist twenty years ago, and the filtering out of those men will impact the subsequent upgrades.

You can argue your point all you want, but the level of risk upgrading in AS programs is certain to decrease with each passing year and new selection tools.

BTW, I am now in Tibet, so don't expect a quick response to any reply.
Posted 4/17/2016 4:58 PM (GMT 0)
It all boils down to the definition of "success". The point of AS, as I understand it, is twofold: First, it is to differentiate between the "probably indolent" from the "probably need treatment" favorable risk men. Second, it is to track the progression of the "probably need treatment" group into aggressive treatment when warranted.

Success is not defined by how many men stay on AS for 5, 10, 15 years. It IS probably best defined in terms of the totality of long term outcomes, best answered by the question, "what is AS's effect, across all patients, of PC-specific mortality at various long-term mileposts?"
Posted 4/17/2016 5:24 PM (GMT 0)
AS FUNDAMENTAL #3: Some men who originally qualify for AS end up moving onward at a later date to a deferred treatment if signs indicate degradation in case characteristics. These men with deferred treatment are also “AS success stories!” (Please study and understand this PC Infolink article if you are confused by that statement: prostatecancerinfolink.net/2010/10/19/understanding-your-clinicians-mindset-about-active-surveillance/) The program worked for them, too, by showing them if and when treatment was appropriate. Complementary research has demonstrated that men on AS who move to deferred treatments have essentially the same outcome as those who sought immediate treatment.
Posted 4/18/2016 12:13 AM (GMT 0)
Why can't a guy argue till the the cows come home if he wants…Who made anyone an arbiter of another ones views when is a real possibility both are wrong…by adamantly arguing the negativity of another simply makes it easier for you do argue your pov... tricking yourself into believing you are on the "correct" side of an argument..
A parable…don't get nervous folks…your traditions are safe…any way two alpha males…rams in this instance are butting horns over who gets to mate with the female…As they lock horns in this silly battle… a 3rd male ram quietly proceeds to the female and mates with here... turn
Posted 4/18/2016 12:15 AM (GMT 0)
JackH, thanks for clarifying.
JohnT, the tone of my response to you was harsher than it seemed at the time. No offense intended.
ASAdvocate, I did not mean to ruffle your feathers, my apologies. We are all on the same side. Enjoy your trip

be well all

back to lurking...
Posted 4/18/2016 12:46 AM (GMT 0)
Dan,
no offense taken,
This is the Klotz data from 2014 taken directly from his report. I don't know where the 28% mortality rate came from, but his data shows 1.5% mortality at 15 years, the same as low risk patients treated immediately.

Here are the results as reported in the most recent publication:
844/993 patients (85.0 percent) were still living at the time of the analysis.
149/993 patients (15.0 percent) had died of all causes.
15/993 patients (1.5 percent) had died of prostate cancer.
Among the 819 surviving patients for whom precise data are available, median follow-up time from initial biopsy to date is 6.4 years (range, 0.2 to 19.8 years)
The 10-year actuarial prostate cancer-specific survival rate is 98.1 percent.
The 15-year actuarial prostate cancer-specific survival rate is 94.3 percent.
13/978 additional patients (1.3 percent) who did not die of prostate cancer developed metastatic disease.
9/13 patients are alive with confirmed metastases.
4/13 patients died of other causes.
Over time, the percentages of patients who remain untreated and on active surveillance are
75.7 percent at 5 years
63.5 percent at 10 years
55.0 percent at 15 years
The cumulative hazard ratio for non-prostate-cancer-specific to prostate cancer-specific mortality was slightly higher than 9 : 1.
Klotz et al. conclude that:
Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8 percent of patients have developed metastatic disease, and 1.5 percent have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention.
Posted 4/18/2016 4:15 PM (GMT 0)

John T said...
I don't know where the 28% mortality rate came from, but his data shows 1.5% mortality at 15 years, the same as low risk patients treated immediately.


JohnT, the referenced data is not relevant to this conversation. Dan0 mentioned, in another thread, a study by Popiolek about Watchful Waiting (importantly, something very different than Active Surveillance), and that the PC mortality there was 11% at 15 years and 28% at 20 years. Klotz mentions this study in some of his publications and highlights that men on WW are not offered delayed definitive interventions. Klotz emphasizes that the differences in WW and AS fully explain these deltas.

Post Edited (JackH) : 4/18/2016 10:18:05 AM (GMT-6)

Posted 4/18/2016 6:52 PM (GMT 0)
Hi Jack,
Please forgive my ignorance, but what is the difference between watchful waiting and active surveillance? I am new to this and had been incorrectly assuming that they were the same thing.
Thanks
✚ New Topic ✚ Reply
12