question on recurrence and aggression

I was wondering if there are any studies relating the time to
recurrence and the aggressiveness of the recurring cancer. It would
seem to me, for instance, that if it takes six years for a smidgen of
cancer to reach the point that it is detectable with a PSA test that
any subsequent doubling time would be quite long. Any ideas,
comments?
Dave Perry

Hi Dave,
Your logic seems reasonable. Johns Hopkins did a study about
recurrence after surgery and came up with risk factors for prediction
of lethal cancers after recurrence following surgery.

The risk factors are based on:
· The amount of time, in months, it takes the level of prostate-
specific antigen (PSA) in the blood to double after surgery. The
shorter the time, the higher the risk.
· The elapsed time, in years, from surgery to recurrence as measured
by the PSA test. Again, the shorter the time the higher the risk.
· The Gleason score (2-10), a microscopic measurement of prostate
cancer aggressiveness when viewed under a microscope. Higher scores
reflect more aggressive tumors.

The study created tables involving these variables. These are
available at:

Stephen J. Freedland, MD; Elizabeth B. Humphreys, BS; Leslie A.
Mangold, MS; Mario Eisenberger, MD; Frederick J. Dorey, PhD; Patrick
C. Walsh, MD; Alan W. Partin, MD, PhD
Risk of Prostate Cancer-Specific Mortality Following Biochemical
Recurrence After Radical Prostatectomy JAMA. 2005;294:433-439.

Would other treatments yield the similar results? Very possible as
most treatments debulk primary tumors to a certain degree. At least,
there should be some correlation with this study.

RalphV
pcainaz.org/phpbb



On Aug 17, 8:30 am, djperr...@sbcglobal.net wrote:
> I was wondering if there are any studies relating the time to
> recurrence and the aggressiveness of the recurring cancer. It would
> seem to me, for instance, that if it takes six years for a smidgen of
> cancer to reach the point that it is detectable with a PSA test that
> any subsequent doubling time would be quite long. Any ideas,
> comments?
> Dave Perry

<djperry42@sbcglobal.net> wrote in message
news:1187364635.682478.288490@x40g2000prg.googlegr oups.com...
>I was wondering if there are any studies relating the time to
> recurrence and the aggressiveness of the recurring cancer. It would
> seem to me, for instance, that if it takes six years for a smidgen of
> cancer to reach the point that it is detectable with a PSA test that
> any subsequent doubling time would be quite long. Any ideas,
> comments?
> Dave Perry

The development of cancer is not a linear process. One
reason is just that "doubling" is not linear. If none of the
cancerous cells died, then if it takes 20 generations to
produce the first million cancer cells, it only takes one
generation to produce the second million.

Of course it's not that bad because not all cancer cells
will replicate and many will die.

But there is another reason too why it is not linear.
Cancer is a disease of damaged DNA. The damage is
passed on to each generation of cancer cells and is
progressive. One cell may have 20 mutations. One of
it's "daughter" cells will get the same 20 and may add
5 more. So the disease characteristics change over
time. A cancer that is indolent at one time may stay that
way for a long time, but then become very different and
very aggressive in the future.

For that reason, I think that if a person is using watchful
waiting, it is very important to emphasize the watchful
part.

Alan

Hi Alan,
Question? How long is a generation for cell development?

Also, I'm not certain that Ralph answered Perry's question. The study only
covers greater than three years and is not specific enough as to longer
periods after surgery before recurrence.

One would think that if recurrence comes a long time after surgery that
the cancer might not be as aggressive. The jury is out on this issue as
far as my brother is concerned. He was 59yrs old, PSA 6.3 Gleason 8
unknown stage. Had RP followed immediately by 36 EBRT. Undetectable for 8
years and now has had a 1.3 a little over a month ago and a month later a
1.5 psa.
He is monitoring his psa for doubling time for the time being. When he
determines his doubling time I will advise you-all. He is presently at
John Hopkins Medical Center reference a case study for spinal injuries
that occurred to him from an aircraft accident. He is also consulting with
Brady Urology reference his recurrence.
Ron S.

"ronju99" <jlspane@nospam.verizon.net> wrote in message
news:b4240e90b0f412b27ef9b97a9e026802@localhost.ta lkaboutsupport.com...
> Hi Alan,
> Question? How long is a generation for cell development?

I have read that prostate cells replicate on average in about 59 days
in a test tube. However, I don't think anyone knows how long it
averages in the living body. There may be chemicals circulating
in the body that up or down regulate the replication rate as compared
to the test tube rate.

> Also, I'm not certain that Ralph answered Perry's question. The study only
> covers greater than three years and is not specific enough as to longer
> periods after surgery before recurrence.

I think Ralph was trying to answer an underlying question - not about
how the doubling time varies but what are the factors to worry about
when considering whether the cancer will become dangerous or
not. Doubling time is just one of those.

> One would think that if recurrence comes a long time after surgery that
> the cancer might not be as aggressive. The jury is out on this issue as
> far as my brother is concerned. He was 59yrs old, PSA 6.3 Gleason 8
> unknown stage. Had RP followed immediately by 36 EBRT. Undetectable for 8
> years and now has had a 1.3 a little over a month ago and a month later a
> 1.5 psa.

Your logic sounds right, but only in average cases. In other
words, patients whose PSA increases immediately after treatment
might, on average, have more aggressive cancers than patients
whose increase only occurs after many years.

But the problem is, each patient's cancer is different and your brother's
cancer today might be different too from what it was 1, 2, or 5 years
ago. Averages may not give much guidance here.

It is possible that your brother's cancer at a very slow, steady
rate during the 8 years during which the PSA was undetectable
until it finally reached a point where it is detectable.

However it's very possible, and it even seems to me to quite likely
(remember I'm no doctor or scientist - this is a layman's "seems
to me") that your brother's cancer didn't grow at all for a long
time and is only now growing faster. Perhaps some change
occurred in the DNA that made the cancerous cells less amenable
to attack from the immune system and so the rate of cancer
cell death has dropped and the cancer is growing faster.

> He is monitoring his psa for doubling time for the time being. When he
> determines his doubling time I will advise you-all. He is presently at
> John Hopkins Medical Center reference a case study for spinal injuries
> that occurred to him from an aircraft accident. He is also consulting with
> Brady Urology reference his recurrence.
> Ron S.

On the one hand, I think it makes sense to try to determine the
rate of PSA growth. Once hormone therapy starts, it is no
longer possible to measure anything until the HT stops working,
which, if your brother is lucky, may not happen for many, many
years.

On the other hand however, the studies appear to show that
HT is more effective when started early than when started late.

Over the years, I do recall a couple of guys on this newsgroup
who had detectable PSA's after treatment in the 0-3 range,
who did not seem to be progressing. But they are a distinct
minority.

This is something he needs to discuss with his doctor. The
folks at Johns Hopkins will know vastly more about this than
I do.

Best of luck to him.

Alan

On 17 Aug 2007, you wrote in alt.support.cancer.prostate:

>
> "ronju99" <jlspane@nospam.verizon.net> wrote in message
> news:b4240e90b0f412b27ef9b97a9e026802@localhost.ta lkaboutsupport.com...
>> Hi Alan,
>> Question? How long is a generation for cell development?
>
> I have read that prostate cells replicate on average in about 59 days
> in a test tube. However, I don't think anyone knows how long it
> averages in the living body. There may be chemicals circulating
> in the body that up or down regulate the replication rate as compared
> to the test tube rate.
>
>> Also, I'm not certain that Ralph answered Perry's question. The study
>> only covers greater than three years and is not specific enough as to
>> longer periods after surgery before recurrence.
>
> I think Ralph was trying to answer an underlying question - not about
> how the doubling time varies but what are the factors to worry about
> when considering whether the cancer will become dangerous or
> not. Doubling time is just one of those.
>
>> One would think that if recurrence comes a long time after surgery
>> that the cancer might not be as aggressive. The jury is out on this
>> issue as far as my brother is concerned. He was 59yrs old, PSA 6.3
>> Gleason 8 unknown stage. Had RP followed immediately by 36 EBRT.
>> Undetectable for 8 years and now has had a 1.3 a little over a month
>> ago and a month later a 1.5 psa.
>
> Your logic sounds right, but only in average cases. In other
> words, patients whose PSA increases immediately after treatment
> might, on average, have more aggressive cancers than patients
> whose increase only occurs after many years.
>
> But the problem is, each patient's cancer is different and your
> brother's cancer today might be different too from what it was 1, 2,
> or 5 years ago. Averages may not give much guidance here.
>
> It is possible that your brother's cancer at a very slow, steady
> rate during the 8 years during which the PSA was undetectable
> until it finally reached a point where it is detectable.
>
> However it's very possible, and it even seems to me to quite likely
> (remember I'm no doctor or scientist - this is a layman's "seems
> to me") that your brother's cancer didn't grow at all for a long
> time and is only now growing faster. Perhaps some change
> occurred in the DNA that made the cancerous cells less amenable
> to attack from the immune system and so the rate of cancer
> cell death has dropped and the cancer is growing faster.
>
>> He is monitoring his psa for doubling time for the time being. When
>> he determines his doubling time I will advise you-all. He is
>> presently at John Hopkins Medical Center reference a case study for
>> spinal injuries that occurred to him from an aircraft accident. He is
>> also consulting with Brady Urology reference his recurrence.
>> Ron S.

The recurrence of PCa and its aggressiveness would,in my opinion (and I am
a PCa patient and not a medical physician)depend upon the individual. What
has been said here is logical and the patient is always advised to seek
individual, proper medical advice. Any treatment decisions should be made
in concert with medical advice - re what is best for me given these facts?

I will use my own case as an example of what I consider to be aggressive
cancer. With a PSA rising over the previous 2 years and one of 7.1 in 2005
I had a biopsy of 10 cores, 1 positive, 5% tumor volume Gleason 3+4 or 7
and a clinical stage of T1c. After a RRP in Dec 2005 the path report came
back T3 bilateral involvement 20% tumor extraprostatic extension, HG PIN, 4
positive margins but no seminal vesicle involvement. Three months after the
RRP my first PSA was 0.87 - the surgery did not get all of the cancer. On
to the Radiation oncologist, my second PSA four weeks later was 1.1 .
Continuing on in this way my PSA doubling time would have been slightly
over 4 months.I did the salvage radiation and the HT with Lupron as a mono
therapy.I continue with the Lupron. So far my PSA's have been <0.1 or
undetectable using the assay they use here - not ultrasensitive.

In consultation with the rad onc, the choice of the salvage radiation and
the Lupron was the right choice by me. As stated above the apparent quick
change in the PSA's over a short period of time suggests aggressive cancer.
Would the PSA continue to rise? I don't know because I didn't wait to find
out. Omitting other symptoms or tests, I only had the velocity to go by. In
the discussion in this thread, the only studies I have seen personally are
those mentioned by Ralph, although I will see what I can find.

I have rad a lot about PCa - the patients get more involved, eh? One thing
not mentioned here is the fact that, for some reason, it has been said that
the higher Gleason scores may, in fact, produce less PSA yet be aggressive.

I wish your brother well Ron. Dave, I don't know the specific answer to
your question, but if I find something I will post it here.

Russ

On Aug 17, 11:30 am, djperr...@sbcglobal.net wrote:
> I was wondering if there are any studies relating the time to
> recurrence and the aggressiveness of the recurring cancer. It would
> seem to me, for instance, that if it takes six years for a smidgen of
> cancer to reach the point that it is detectable with a PSA test that
> any subsequent doubling time would be quite long. Any ideas,
> comments?
> Dave Perry

Didn't work that way in my case. I had a board flat PSA in the 9
(NINE) range for several years. First 6-way biopsy was negative.
The biopsy 2 years later was positive in 5% of one core.

I went rad, seeds with IMRT, with 8 months of Lupron. 3 months into
that, my PSA was undetectable.

When the Lupron wore off, my PSA climbed back from "undetectable" to
1, 2, 6, up and up to over 60 at which time I went back on Lupron.
At PSA 20, I was experiencing symptoms from the tumor which was
compressing my windpipe and a blood vessel in my chest. At PSA 40,
It was clearly killing me.

Casodex and Lupron have reversed this.

My question is, what happened? Did the radiation or biopsy ANGER
it?

This has been an incredible adventure.

-kh