How common are late recurrences?

John,

Have you seen the studdy from Johns Hopkins about G6 organ confined people having a 99.6% cure rate wih follow up out to 21 years on some patients? I have a hard time believing them when I read studies like the one you posted. It seems that Pca never stops recurring no matter how many years out you are.

When my urologist told me that my PSA was undetectable at one year I replied, "I guess I'm home free!".

He said, "We like to see 5 years."

Well, it's been 12 and my PSA has doubled from .58 to .92 in 11 months.

Tony, I agree with you. I think that all the studies are immature. Prostate cancer is probably a 15 to 20 year decease. All these studies have median ages in the upper 60s. Most will not live another 15 years. Hence the coin phrase I always here "most men die with PCa and not from it." Who knows how long these men had PCa on average before they were dx. 5 to 10 years maybe. It is a completely different story for those of us dx. at a young age. My PSA at 38 years old was 2.4. So you figure I had it at least 5 years before that. Making mine occur 21 years before my dads was detected when he was 58. I will make my son who is 5 now get a base line at 15 years old and start testing regularly at 20. So having PCa at roughly 32 years old I have no doubt that I have an aggressive version of PCa even though it was G6 organ confined. I don't believe I have a chance in heck of not having it come back unless I drop dead of a heart attack. Which I am hoping for, seriously.

I recently read a study from PCa info. Link. It contained patients with localized PCa and a tumor volume of less then .5cc. They found that 40% of them had circulating tumor cells from PCa. That explains all the supposedly organ confined recurrences to me and shows that it is probably too late for most of us when dx.

However I was told in an email from Epstien at Johns Hopkins that 99.6% of G6 people are cured. I think he and Walsh and Partin probably have been around long enough to see as much of this cancer and it's variations as anyone. I would like to believe him, deep down logic and these late term recurrences we are seeing counter his statement to me.

I think PSA testing is just creating a lot of lead time for us. Not any better chance at cure. This is proven time and time again in study after study that screening does not reduce prostate cancer specific mortality.

Better hope provenge works better in young guys with eariler stage desease.

David I don't subscribe to that idea very much.
I have seen way too many examples of Gleason 8 and 9 guys doing great for just as long as the G6 guys. My predecessor at UsTOO had surgery on his Gleason 8 in 1993 and is doing great. Mike Milken had G9 in that same year and he looks fit as a fiddle. Many more cases that contradict that idea at YANA and here.

This disease is very tricky. Many of our members will never have a relapse regardless of Gleason sum, or stage clinically or pathologically after surgery. And if they do, they still have a better chance of outliving the disease than dying from it.

But back to my point, Once we have the disease, we have to be diligent for the remaining years of our healthy lives.

@Chris, I no longer trust the data from JHU entirely. They are a Urological center and they have reason to suggest such success rates. Just as I could fault a radiation center for suggesting that they have the better solution, I can do the same here. We had a debate here at HW about active surveillance in which studies from Klotz were compared. In Klotz's own statements a G6 man will almost never die of the disease in the first ten years and I agree. But in an interesting twist he didn't say the same thing about at year 20. In fact he indicated that a man with G6 left untreated in the second decade has about a 10% mortality rate due to prostate cancer.

This prompted me to state that "it was well known that more than half of G6 AS guys will eventually abandon AS for an active treatment". Terry Herbert asked me to produce that well known data for which I cannot do so in study. But I still think it's true however that is only my own opinion based on the complete data that's in my little head...

That's a whole different discussion so please let's not debate it here.

Tony

Post Edited (TC-LasVegas) : 11/24/2010 8:36:30 PM (GMT-7)

One of the things I don't like about these studies is that they always have a mix of patients treated over a range of years. In other words they generally have a lot of patients treated in the last 24 months or so fewer treated 10 years ago and very few treated 15 years ago. They then never break down when the recurrences happened. So let's say they only had 8 people who where at the 15 year mark and 3 of them had recurrence. That would be 37% ultimately having recurrence. I would imagine that the researchers would not be that dumb, but who knows.

Tony, I don't think J.H. is embellishing their results. I just don't see why they are using the word "cure"

Post Edited (ChrisR) : 11/25/2010 6:26:44 PM (GMT-7)

The numbers that Tony is referring to from the Klotz AS program is that within 7 years 30% will progress and another 12% opt for treatment without any signs of progression bringing the total up to 42% in 7 years. The 15 year number, if we had one would surely be much larger.
In regards to Chris's comments; I think that G6 tumors are very different from the higher grade tumors in the way they act and progress. The reoccurrance rates are much lower and even with a reoccurrance the chance of matastatis is very unlikely.

Long term reoccurrances with radiation may be different than long term reoccurrances with surgery. Dattoli published a 14 year study of high risk patients treated with seed/IMRT combo. 81% had biochemical free progress at 14 years using a psa of 0.2.
All his charts show reoccurrance increasing to 4 years then flatlining with only 1% of reoccurrances happening after 5 years. All failures were systemic and none were local as all failures underwent additional biopsies. This reoccurrance rate curve is quite different from the surgical reoccurrance rate curves which show a higher rate of late reoccurrances. I have no idea of why the difference. It could be that the rate of local reoccurrance with surgery is higher and with slow growing cancers may not be detectable until years later. The systemic failure rate of 20% has to be the same for both surgery and radiation so the only difference must be the rate of local reoccurrances.
JT

The German paper John T quotes is very interesting. This seems like one shouldn't be too dogmatic about this issue, even though some medical experts might be. A number of thoughts:

1. Most studies use a short followup period. As Tony points out, long term--10-20+ prognosis can't be extrapolated from these. You can't assume that short term followup tells you the whole story.
2. The small number of long term studies have limitations. It's hard to do these studies, any many patients are lost to followup, which can affect the results.
3. It seems likely that late recurrence should be preceded by years of biochemical recurrence. So, it seems likely that after 5 years of "undetectable" PSA, the risk of clinical recurrence in one's lifetime should be low.
4. Gleason score is a predictor of recurrence, but isn't infallible. It is based on a subjective impression of a pathologist. Other predictors are anatomy. Spread to lymph nodes means distant metastatases are likely present. Spread to seminal vesicles also correlates with a high risk of metastatases. Extracapsular extension means risk of local recurrence. Positive margins might also.
5. Prostate cancer is more often slow growing. If someone has a few cells left outside the prostate, it can take a very long time for this to grow up and cause clinical recurrence during your life (see #2).
6. Does "malignant transformation", where a tumor changes to a higher grade, happen? Although some have said that it doesn't, I don't see why it couldn't. It happens with other forms of cancer. For example, someone can have a low grade brain tumor (for example, a grade 1 or 2 astrocytoma) removed by surgery, and then have it recur years later as a high grade malignancy. A prostate tumor could be graded as Gleason 6, but who can say that it isn't harboring a few more malignant cells that will later manifest themselves. So this might be a rare factor in #4 and #5 above.

I'm back on the board after a long trip abroad. I was going to do a review on radiation treatment, and I might do it, but right now I'm catching up on a variety of work. I have to say, that I'm doing so well, prostate-wise, that I'm not thinking about that particular part of my body too much and I'm not coming to the board too much.

Chris,
There us very definitive evidence that prostate becomes more aggressive when it metastasizes. We speak in terms of asking if G6 can become a G7, etc. There is no evidence that it does not either. We can only make assumptions but I would side with Postop's assessment, there is no reason that a DNA mutated cell cannot continue mutating when they multiply. Still, once the disease metastasizes it becomes a new challenge to our oncologists and the risks are much higher. At one speaking engagement Nick Vogelzang mentioned that localized and metastasized prostate cancer do not behave the same way regardless of Gleason score.

In later recurrences there is a higher risk involved for that reason. The in creased mortality rate, even in G6 cancer, speaks for that risk. This is what makes the Klotz comments in the AS study worth considering for all patients.

Tony

SanCarlos,
The article mentions that most don't progress within 3 years, but some do turn into higher grades later. This can be due to missampling or a new higher grade cancer that has no relation to the esixting tumor. I guess the jury is still out with some men having higher grade tumors that evolve after a number of years, but most showing no progression in gleason grade.
JohnT

Carlos

Below is a copy of a post I did in  a different thread.  You may want to go to the links I have listed.

After reading some (not all) of the posts on this subject I decided to do a bit of research. SLoan Ketteing has what they call some "Prediction Tools" that are listed at http://www.mskcc.org/mskcc/html/5794.cfm

At http://www.mskcc.org/mskcc/html/10088.cfm   you can find the information abut how to use the prostate cancer tool

At http://www.mskcc.org/applications/nomograms/Prostate/index.aspx  you select which prostate cancer tool applies to you and then follow the prompts.

The tool asks you for specific information and then gives a percentage prediction of how long you will remain cancer free.  Mine read:

Progression-Free Probability After Surgery	2 Year	99%
	5 Year	98%
	7 Year	97%
	10 Year	96%

I am sure that this is not absolute.  However, it does get rid of some of the guess work