Psa rise post surgery
skeptic
If a high psa, say 10-20 range before treatment is so bad, then why is
a tiny psa after surgery, say 0.2, a sign of doom, so to speak?
If the original (very high) psa is because of prostate cancer and the
prostate is removed, even if there are residual cancer cells left, why
are they regarded as so dangerous when there are no tumors present and
only a very very low psa (but not undetectable)?
Why isn't watchful waiting considered in that situation, instead of
continued agressive treatment?
Is it possible for mets/tumors to become aggressive with such a low
psa...assuming it stays fairly low but still considered high for post-
op?
(I hope this doesn't come across as total ignorance.....I'm fairly
well studied on this, as all of us are....it's just hard to phrase
correctly)
ron
If the surgeon really got it all, then post-op PSA should be <0.01 ng/
ml. Any detetctable PSA indicates that the surgeon didn't get it
all. In turn, that may mean that a) some tissue (cancerous, benign)
was left behind or b) the disease was not localized to begin with.
One detetctable PSA reading post-surgery tells little more than that,
it does not spell doom. What would be more meaningful would be a
series of post-op PSA values so that a doubling time can be
determined. A doubling time of 5-10 years suggests that benign tissue
was left behind and AS is an option followed by many/most in this
case. A doubling time of 3 years or less suggests more serious
consequences with intervention of some sort a likely option...ron
JimBob
Skeptic,
In my case I had my RRP in late 2003. PSA's were OK for a year or so
then started to creep up. My uro-doc told me that there might well have
been a small piece of missed tissue and if so hopefully it remained in
the prostate bed. He didn't see any necessity for immediate treatment
unless the PSA started to rise so "watchful waiting" was the suggested
TX at that time.
In late 2007 my PSA jumped to .6 from the previous .2 and thats when my
uro-doc decided to act. I had a ProstaScint scan that failed to find any
major localized "hot spots" so the assumption was a a small spot of
tissue left in the prostate bed. At that point I did RT and within 2
weeks of completing treatment my PSA was back down to <.2 and my last
test about a month ago was <.1 .
Actually my uro-doc and rad-onc were pretty much relaxed about the whole
thing and there never was a sense of urgency to do anything until my
physical situation dictated it. I guess what I'm trying to say that
contrary to your post it isn't always "doom and gloom" , it just seems
to get the most "press" ......
JimBob
"Master of the Sr. Moment"
rosbif
<Jim...@invalid.comcast.net> wrote:
>skeptic wrote:
>> Can someone explain psa rise post surgery vs. psa rise pre surgery?
>> If a high psa, say 10-20 range before treatment is so bad, then why is
>> a tiny psa after surgery, say 0.2, a sign of doom, so to speak?
>> If the original (very high) psa is because of prostate cancer and the
>> prostate is removed, even if there are residual cancer cells left, why
>> are they regarded as so dangerous when there are no tumors present and
>> only a very very low psa (but not undetectable)?
>> Why isn't watchful waiting considered in that situation, instead of
>> continued agressive treatment?
>> Is it possible for mets/tumors to become aggressive with such a low
>> psa...assuming it stays fairly low but still considered high for post-
>> op?
>> (I hope this doesn't come across as total ignorance.....I'm fairly
>> well studied on this, as all of us are....it's just hard to phrase
>> correctly)
>
Not at all, I think it's an excellent question and one that still
appears to confound everyone (please let him post who is not
confounded!). More generally, to what extent is the natural history
of PCa altered by the various treatments offered?
>
>Skeptic,
>
>In my case I had my RRP in late 2003. PSA's were OK for a year or so
>then started to creep up. My uro-doc told me that there might well have
>been a small piece of missed tissue and if so hopefully it remained in
>the prostate bed. He didn't see any necessity for immediate treatment
>unless the PSA started to rise so "watchful waiting" was the suggested
>TX at that time.
>
>In late 2007 my PSA jumped to .6 from the previous .2 and thats when my
>uro-doc decided to act. I had a ProstaScint scan that failed to find any
>major localized "hot spots" so the assumption was a a small spot of
>tissue left in the prostate bed. At that point I did RT and within 2
>weeks of completing treatment my PSA was back down to <.2 and my last
>test about a month ago was <.1 .
>
>Actually my uro-doc and rad-onc were pretty much relaxed about the whole
>thing and there never was a sense of urgency to do anything until my
>physical situation dictated it. I guess what I'm trying to say that
>contrary to your post it isn't always "doom and gloom" , it just seems
>to get the most "press" ......
>
>
>JimBob
>"Master of the Sr. Moment"
Thanks for posting this up JimBob. What interests me most is your
coming relatively late (4 years post RP?) to SRT and at a PSA level
(0.6) high enough to have made some shudder...whatever, it looks like
a really good result for you. Long may it continue.
JimBob
>
>> Skeptic,
>>
>> In my case I had my RRP in late 2003. PSA's were OK for a year or so
>> then started to creep up. My uro-doc told me that there might well have
>> been a small piece of missed tissue and if so hopefully it remained in
>> the prostate bed. He didn't see any necessity for immediate treatment
>> unless the PSA started to rise so "watchful waiting" was the suggested
>> TX at that time.
>>
>> In late 2007 my PSA jumped to .6 from the previous .2 and thats when my
>> uro-doc decided to act. I had a ProstaScint scan that failed to find any
>> major localized "hot spots" so the assumption was a a small spot of
>> tissue left in the prostate bed. At that point I did RT and within 2
>> weeks of completing treatment my PSA was back down to <.2 and my last
>> test about a month ago was <.1 .
>>
>> Actually my uro-doc and rad-onc were pretty much relaxed about the whole
>> thing and there never was a sense of urgency to do anything until my
>> physical situation dictated it. I guess what I'm trying to say that
>> contrary to your post it isn't always "doom and gloom" , it just seems
>> to get the most "press" ......
>>
>>
>> JimBob
>> "Master of the Sr. Moment"
>
>
> Thanks for posting this up JimBob. What interests me most is your
> coming relatively late (4 years post RP?) to SRT and at a PSA level
> (0.6) high enough to have made some shudder...whatever, it looks like
> a really good result for you. Long may it continue.
Well , like I said in my post my PSA had just been hanging in the .2
neighborhood for what seemed like "ever" and I was a little anxious at
times. My uro-doc ( also surgeon ) just kept telling me not to get
freaked out and that if it hit .3 then he would advise SRT.
What got the train moving was the 6 month jump from .2 to .6 , believe
me when I say that all was relatively ok at a steady .2 for 2 1/2 years
or so but the .6 surprised even my doc's. I just had to have faith in
what I was being told and trust the folks treating me. Ultimately it
appears that they were correct in my ongoing DX's and TX's .
I'm sure that there are cases somewhat like mine that end up killing
folks earlier than should be but I also believe that's where a lot of
the "doom and gloom" publicity comes from. Self study on this disease
is a necessity but you can't let yourself get overwhelmed by one side or
the other. In retrospect I probably was much to far on the optimistic
side in the beginning. The original DX didn't phase me much nor the
subsistent "flair-up" and SRT. I've seen writings both here and in some
"blogs" that suggested to me that "some" Pca patients were suffering far
more from perceived problems and an unknown future than from the disease
itself.
Steve Kramer
news:1_WdnZZxivmcaAfV...@comcast.com...
> At that point I did RT and within 2 weeks of completing treatment my PSA
> was back down to <.2 and my last test about a month ago was <.1 .
Great news, JimBob. Anything below 1.5 after RT is VERY good news.
--
PSA 16 10/17/2000 @ 46
Biopsy 11/01/2000 G7 (3+4), T2c
RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins
PSA <.1 <.1 <.1 .27 .37 .75 PSAD 0.19 years
EBRT 05-07/2002 @ 47
PSA .34 .22 .15 .21 .32 PSAD .056 years
Lupron 07/03 (1 mo) 8/03 and every 4 months there after
PSA .07 .05 .06 .09 .08 .132 .145 PSAD 1.4 years
Casodex added daily 07/06
PSA <0.04, <0.05, <0.04, <0.04, <0.1 2/12/08
Illegitimati non carborundum
JimBob
> "JimBob" <Jim...@invalid.comcast.net> wrote in message
> news:1_WdnZZxivmcaAfV...@comcast.com...
>
>
>> At that point I did RT and within 2 weeks of completing treatment my PSA
>> was back down to <.2 and my last test about a month ago was <.1 .
>
> Great news, JimBob. Anything below 1.5 after RT is VERY good news.
>
>
>
Steve,
Thank-you, thank-you
Nice to hear about the post RT 1.5 number , I wasn't aware of that stat.
I'm adding that to my "most optimistic" data store !!!
Apparently Elvis will not be "leaving the building" anytime soon , at
least due to Pca anyway ..... Now I just need to remember where I left
that big bottle of vodka !!!!
Just
<skr...@cinci.rr.com> wrote:
>"JimBob" <Jim...@invalid.comcast.net> wrote in message
>news:1_WdnZZxivmcaAfV...@comcast.com...
>
>
>> At that point I did RT and within 2 weeks of completing treatment my PSA
>> was back down to <.2 and my last test about a month ago was <.1 .
>
>Great news, JimBob. Anything below 1.5 after RT is VERY good news.
Steve,
JimBob had RRP in 2003 + RT in 2007. Very good news for him is to
remain "undetectable"... right?
Just
Steve Jordan
> JimBob had RRP in 2003 + RT in 2007. Very good news for him is to
> remain "undetectable"... right?
We should be certain that the terms we use are understood by all concerned.
To me, depending upon such PCa specialists as Scholz, Lam and Strum, et
al., "undetectable" is defined as PSA =/< 0.05 ng/mL.
No, I don't want to restart the argument about what is UDPSA. I know
what it is, and using it as defined above has served me well. Others,
too. Those who don't "believe" in it can suit themselves.
Regards,
Steve J
"Men occasionally stumble on the truth, but most of them pick themselves
up and hurry off as if nothing had happened."
-- Sir Winston L. S. Churchill
skeptic
To explain a little more detail about my post, I did find out I had
the dreaded lymph node involvement after surgery and was advised to
immediately go on ADT, as my 3 week post-op psa was .90 and climbed to
1.37 within a matter of weeks after that......not a good sign, I very
well know. :(
I'm on lupron only and it whacked it down to undetectable within 3
months (.03).
My med onc doesn't seem concerned about any additional treatment and
is pleased.
So does the lupron really do anything to halt the cancer spread or
does it just lower psa?
Ed Friedman
>
> To explain a little more detail about my post, I did find out I had
> the dreaded lymph node involvement after surgery and was advised to
> immediately go on ADT, as my 3 week post-op psa was .90 and climbed to
> 1.37 within a matter of weeks after that......not a good sign, I very
> well know. :(
> I'm on lupron only and it whacked it down to undetectable within 3
> months (.03).
> My med onc doesn't seem concerned about any additional treatment and
> is pleased.
> So does the lupron really do anything to halt the cancer spread or
> does it just lower psa?
>
Skeptic,
Lupron lowers your level of testosterone (T), which results in most of
your cancer cells dying due to calcium overload. However, prostate
cancer is a heterogeneous mix of cells. Some cells will slowly die off,
where their rate of growth is only slightly less than their rate of
death. Some cells will slowly increase in number, where their rate of
growth is only slightly greater than their rate of death. However,
those cells that thrive under the conditions of androgen deprivation are
the ones that typically are the cause of death and which are rightfully
the most feared. There are various reasons why such cells are able to
thrive - high levels of the anti-apoptotic protein Bcl-2 is the reason
for over 65% of the known androgen independent cells. Other mutations,
such as in the pro-apoptotic protein p53 are also bad news.
Ed Friedman
len
Lupron lowers PSA by depriving prostate cells of androgens which allow
them to grow. In a case like yours, those cells are almost
certainly cancer cells. So it stops the spread of your cancer.
Unfortunately, there are probably other prostate cancer cells present
which don't need those androgens to grow. Opinions differ about
whether such cells develop as mutations from hormone sensitive cancer
cells or whether they were just there to start. In the first case,
drugs like Lupron might further slow the spread of the cancer. In the
second case, they wouldn't, they would just suppress symptoms until
the resistant cells took over.
What is known is that drugs like Lupron can keep men symptom free for
some time, but not indefinitely. Also, how long they work is quite
variable. If you are doing well on them, you might as well assume
that they will continue working. If they stop, you can worry about
it when it happens. It may be quite a long time from now, and you may
have died of something else first.
Meanwhile, there is ongoing research, and we all hope that drugs will
be developed which will destroy both the hormone sensitive and hormone
insensitive cells and thus cure the disease. Recent suggestions that
the hormone insensitive cells survive by making their own testosterone
seem promising. In that case, interfering biochemically with that
process may provide a cure.
Steve Kramer
news:i3nm949s2ltecciqb...@4ax.com...
Yeah, and even better news is for him to flat line for the rest of his life.
Steve Kramer
news:3976598e-3706-47f5...@1g2000pre.googlegroups.com...
So does the lupron really do anything to halt the cancer spread or
does it just lower psa?
==> Lupron starves cancer cells. Some die. Some go dormant. Some
eventually morph. While the cells are dead and/or dormant, cancer does not
grow.
Steve Kramer
news:rrKmk.16$HH...@news.uchicago.edu...
I hope I live long enough to understand in full just one of your posts. :-)
e...@math.uchicago.edu
>
> I hope I live long enough to understand in full just one of your posts. :-)
Steve,
If you tell me what you don't understand, I'll be happy to try to
explain it to you. One thing that you should realize is that the
question of whether "androgen independent" PCa exists before androgen
deprivation or whether it develops under it is a no-brainer.
Basically, you are talking about the Lamarck theory of evolution
(organisms change their genetic makeup in response to their
environment) versus the Darwin theory of evolution (natural selection
gives a selective advantage to those existing mutations which promote
survival). Darwin won that debate over a 100 years ago. It is
pathetic that supposedly educated doctors are bringing up these old
arguments to try to explain "androgen independent" PCa. The major
defect in their thought process is that they consider testosterone a
"survival factor" for PCa. This is in spite of the fact that hormones
have never been proven essential for any type of human cancer,
although they can affect the rate of growth and the rate of apoptosis
(cell death) in some cases. The removal of testosterone simply
increases the rate of apoptosis by flooding the cells with calcium
ions. Normal prostate cells die at exactly the same rate whether you
remove androgen or whether you use a drug to force calcium into them.
If you remove androgen, you can save 70% of those cells that would
otherwise die by giving a drug that blocks calcium intake. Finally,
if you take PCa that is "androgen sensitive" and add a vector of DNA
for the anti-apoptotic protein Bcl-2, then you instantly transform
these cells into becoming "androgen independent". Clearly, none of
this is consistent with testosterone being a "survival factor" for
PCa.
Ed Friedman
Ed Friedman
ron
On Aug 11, 5:05 pm, e...@math.uchicago.edu wrote...snip...
> One thing that you should realize is that the
> question of whether "androgen independent" PCa exists before androgen
> deprivation or whether it develops under it is a no-brainer.
That catches my attention, I didn't thing anything was crystal clear
with regard to PCa.
> Basically, you are talking about the Lamarck theory of evolution
> (organisms change their genetic makeup in response to their
> environment) versus the Darwin theory of evolution (natural selection
> gives a selective advantage to those existing mutations which promote
> survival). Darwin won that debate over a 100 years ago.
So you arguing that AI develops in response to ADT? Such a position
is inconsistent with Bruchovsky's work with PCa stem cells (see for
example, J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):501-11; Effects
of intermittent androgen suppression on the stem cell composition and
the expression of the TRPM-2 (clusterin) gene in the Shionogi
carcinoma; Akakura K, Bruchovsky N, Rennie PS, Coldman AJ, Goldenberg
SL, Tenniswood M, Fox K.). That does not mean that your position is
wrong. It seems likely that there are multiple entry points into the
PCa dynamic. Different PCa tumors likely have significantly different
DNA and as a consequence would have significantly different origins
and preferred treatments.
> It is
> pathetic that supposedly educated doctors are bringing up these old
> arguments to try to explain "androgen independent" PCa. The major
> defect in their thought process is that they consider testosterone a
> "survival factor" for PCa.
My view is that most investigators who work in the area see DHT,
rather than T, as the major stimulus for prostatic, cancerous and
benign, cell growth. The purported observation that 5AR genetically
deficient populations such as the guevedoces do not suffer from BPH or
PCa seems to corroborate this position. Along these lines, it is
unfortunate that so few men on ADT measure their T level, and even
fewer measure DHT.
> This is in spite of the fact that hormones
> have never been proven essential for any type of human cancer,
> although they can affect the rate of growth and the rate of apoptosis
> (cell death) in some cases.
Is the converse of that statement true? Has it ever been proven that
hormonal levels cannot produce or eradicate tumors?
> The removal of testosterone simply
> increases the rate of apoptosis by flooding the cells with calcium
> ions. Normal prostate cells die at exactly the same rate whether you
> remove androgen or whether you use a drug to force calcium into them.
The reduction in serum androgen levels may or may not influence intra-
prostatic androgen levels. The latter is what is of primary concern.
e...@math.uchicago.edu
Ron,
It is always a pleasure to discuss science with you. You raise some
good points.
First, after years of applying my model to all of the observed
findings in PCa, things are in fact crystal clear. I have yet to find
any experimental data that does not fit my model in a straightforward
way.
Now, on to the specifics. First, to say that AI develops as a result
of ADT is inaccurate. There are always AI cells present, but they
will not dominate the population unless the other PCa cells are
eliminated. ADT allows one to eliminate non AI cells, eventually
leaving only AI cells. This is why the recent study showed that early
continual ADT increased the rate of death from PCa. Saying there are
no AI cells present until being exposed for some time to ADT is the
Lamarck view. The Darwin view is that AI cells are always present,
and when using ADT, such cells have a selective advantage over other
cells.
The Bruchovsky paper is quite interesting. Throughout it they make
the assumption that AI is related to iAR and focus all of their
attention on that. They also make the assumption that they are
starting with a homogenous genetic set of cells, but the reality is
that all tumors contain some genetic variations in some of their
cells. Once you realize that for PCa to become AI only means that it
resists apoptosis under conditions of ADT, then it is clear what
happens. When using ADT, you select cells that resist apoptosis under
those conditions. This means increased anti-apoptotic proteins, such
as Bcl-2; mutations that affect pro-apoptotic proteins, such as p53;
and mutations that affect any of the proteins needed to actually
perform the process of apoptosis. Another couple of possiblities that
my model indicate might be occurring is increased number of iAR, since
that will keep out the calcium that is responsible for apoptosis, and
seeming paradoxically, an increased number of mAR, since that will
amplify the amount of Bcl-2 produced from the small amount of T that
is still present.
I discuss the fact that men without DHT never get PCa in my first
paper. From my model, apoptosis occurs whenever there is a growth
imbalance in the ratio of mAR to iAR (where you have to multiply iAR
by 5 when DHT is present). PCa will still start in men with no DHT,
but it will almost always have a rate of growth less than its rate of
apoptosis, because the imbalance in favor of mAR will result in high
levels of Fas always being present. This will result in those men
having smaller than normal prostates as well as almost no chance of
PCa.
However, it is very simplistic to demonize DHT. Dr. Leibowitz told me
that there were some men treated with high dose DHT whose PSA dropped
almost to 0, then bounced back strong. When DHT was removed, the PSA
dropped once again. The easiest way to understand all of this is to
view the androgen receptors as the way for the body to eliminate
defective prostate cells. When there is close to a normal balance of
mAR to iAR, then T (assuming it is converted to DHT) has little effect
on inducing apoptosis. However, if both mAR and iAR are defective
then you have the equivalent of ADT and apoptosis occurs. If iAR is
defective or an unusually high ratio of mAR to iAR, then lots of Fas
will be produced, resulting in apoptosis. Finally, if mAR is
defective or an unusually low ratio of mAR to iAR, then DHT will
result in lots of AS3, which prevents cell division and eventually
results in apoptosis. Ordinarily, increasing the ratio of mAR to iAR
increases the rate of PCa growth in the presence of T, but once you
get above a high enough ratio, androgen then decreases the rate of PCa
growth.
I agree that when on ADT the intracellular concentration of DHT is
key. That is why it is crazy that all doctors don't do ADT with the
combination of Lupron, Casodex, and Proscar used by Dr. Leibowitz.
One interesting note is that T-BSA has been shown to be especially
powerful in inducing apoptosis. When LNCaP is transplanted into
castrated mice, T-BSA equivalent to 2900ng/dl of T results in a 60%
reduction in the tumor size within 30 days. Incredibly, when they
went up 100-fold of T-BSA to the equivalent of 290,000ng/dl of T, they
observed absolutely no ill effects on the mice, but an even greater
increase in the amount of apoptosis. In theory, using ultra high
levels of T in conjunction with Casodex and Proscar might be the
equivalent of T-BSA plus castration. However, as far as I know, no
doctor has yet tried this combination in humans.
Ed Friedman
e...@math.uchicago.edu
> hormonal levels cannot produce or eradicate tumors?
>
Ron,
Sorry I didn't answer this part in my previous post. If my model is
correct, then it is possible to construct a genetic makeup for PCa
that will either have increased cell growth or increased cell death
depending on the makeup of the hormone receptors. This is because for
each of the hormones (testosterone, progesterone, and estradiol) there
are two receptors acting in opposition to each other. In reality, for
men with normal genetic makeup, all of the hormones initially increase
the rate of cell death. If their levels are high enough, e.g. a
typical teenage level, then PCa can not proliferate. As men age, and
the hormone levels drop, then PCa can start up. Once it starts up,
Darwinian evolution occurs, and each mutation that protects it from
the hormones has a selective growth advantage. By the time a man
becomes terminal, it is likely that the PCa will increase its growth
rate in response to each of the three main hormones. So to answer
your question, in theory it is possible to have PCa cells die solely
by using hormones, but in practice in will never happen unless you can
start increasing hormone levels at the point that there is only a few
cancer cells and no mutations yet.
On another note, there seems little doubt that the initiating step in
causing PCa is high local levels of estradiol (same for breast
cancer). Continual high levels of estradiol immortalize those cells
by producing oncogenes such as Myb which cause the cells to divide and
producing telomerase which allows the cells to divide without
shortening their telomeres. However, even though this initiates PCa,
the hormone levels (especially T) must be low enough in order for PCa
to proliferate.
Also, to clarify a bit the difference between my view on PCa and that
of the Bruchovsky paper is that in their paper every time they applied
ADT and the tumor shrank, they said it's not AI yet. When it finally
does become AI, they try to figure out why it became so on that
particular round of intermittent ADT. From my point of view, every
time they apply ADT, they are killing many cells, freeing up the
existing AI cells to grow more freely without the constraint found by
cells in the interior of a tumor trying to multiply (usually only the
outer edge of the tumor freely multiplies). Also, some cells will
have a growth rate slightly less than their rate of cell death, and
each round of ADT will have less and less of those cells. There are
also some cells that have a growth rate slightly greater than their
rate of death, and they will coexist with the AI cells once the tumor
is officially declared to be AI.
Ed Friedman
BlDn10
still here. Although I certainly don't understand the seemingly
endless levels of biochemistry, I am impressed that your model
consistently stands up to clinical results. On one hand I am
encouraged that someone might be on the right track, but, if I am
interpreting your model correctly, I am disheartened at the prospects
of a Tx coming out of it any time soon. The reason being that you have
shown that almost every case is unique - what works for Mr. A. makes
Mr. B worse; what worked for Mr. A, early on actually makes him worse
at some other time. And then it might switch back again. Right? Do we
have the lab capabilities to identify all the various factors that are
effective at any given time? I know you can't give medical advice but
can you speculate how your model might be used in a Tx protocol?
Ed, where does one's immune system come into play? My simplistic
"model" is that one's immune system can keep a certain amount of
cancer at bay, but if there is an insult to that system and/or the
tumor load gets over the line - you develop cancer. In my case I
obviously have a strong immune system because I NEVER get sick other
than a cold or 2 a year. Other than my PCa I haven't been sick in bed
in decades. My PCa Dx made me question that. But w/i 3 mos. both my
brother and 1st cousin were Dx'd, and I had an uncle w/ PCa. So I say
that even my robust immune system could not overcome genetics.
Likewise, despite a pre-op PSA 33 and SVI, post-op my PSA very slowly
rose over 4 years to 1.0. Then 1 1/2 years to 2, now 6 mos. to 3. I
think I could handle PCa up to the 1.5 - 2 range w/o Tx, but over 2
is just too much. I wonder if I could have ADT just enough to keep me
in the sweet spot - not even try to take it to undetectable. I guess I
would call that Limited Intermittent HDT. Does that make any
sense?
Bill/Memphis