The Latest for the Anti-Testers to Ignore

Bartsch G,, et al., "Tyrol Prostate Cancer Demonstration Project: early
detection, treatment, outcome, incidence and mortality." BJU Int. 2008
Apr;101(7):809-16.

From Pub Med, a service of the US National Library of Medicine at
www.pubmed.gov

Pub Med ID 18321314

Conclusion: "In the Tyrol region where treatment is freely available to
all patients, where widespread PSA testing and treatment with curative
intent occurs, there was a reduction in prostate cancer mortality rates
which was significantly greater than the reduction in the rest of
Austria. This reduction in prostate cancer mortality is most probably
due to early detection, consequent down-staging and effective treatment
of prostate cancer."

Note: the Tyrol study was begun in 1988 and has been reported
periodically. It consistently demonstrates that PSA testing saves lives.

Regards,

Steve J

"No patient in a civilized society should present with a PSA level that
is in double digits. Routine PSA testing on a yearly basis (initially)
would virtually eliminate any advanced presentation of prostate cancer,
increase the number of patients presenting with true organ confined
prostate cancer, increase our ability to cure this disease, decrease health
care costs from having to treat more advanced presentations, improve
productivity of those men diagnosed with prostate cancer and of course most
importantly improve the quality and the duration of life with men diagnosed
with this illness."
-- Stephen B. Strum, MD
Medical oncologist
PCa Specialist

On Sun, 27 Apr 2008 15:43:17 -0400, Steve Jordan wrote
(in article <tH4Rj.731$152.34@newsfe12.phx>):

> Bartsch G,, et al., "Tyrol Prostate Cancer Demonstration Project: early
> detection, treatment, outcome, incidence and mortality." BJU Int. 2008
> Apr;101(7):809-16.

[snip]

I have been listening to "Fooled by Randomness" by Nicholas Taleb. He makes
some interesting points, particularly about sample bias. Since a high PSA
leads to a biopsy and a biopsy is what determines whether the cancer is
present and/or treated or not, couldn't one say that it was the _biopsy_
which reduced the mortality rate? How would we know that biopsies on a
comparable sample with a lower PSA or no measured PSA wouldn't produce a
comparable or better result, since people don't routinely do them?

I have experienced anomalous fluctiations in my own PSA which can't be
explained by cancer alone and I am aware of anecdotal evidence of people with
high PSA's not having cancer. Then there is the poster with a palpable 1 cm
tumor and a low PSA.

I wonder if a routine biopsy after a certain age shouldn't be recommended in
the same way that a routine colonoscopy is. Note, having had both, I'd much
prefer the biopsy.

--
Dedman

** Posted from http://www.teranews.com **

IMO, most of those who argue against wide spread PSA testing, don't
argue from ignorance. Rather they ask, because of PSA testing how
many men are needlessly treated, how does degraded QOL play into the
equation. Further they argue that the results of the Tyrol and other
similar studies are flawed. The Tyrol experiment has been repeated in
at least 3 other areas. The issue that all of these studies run into
is that they must make assumptions about how many men in the "testing"
region comply and how many men in the adjacent "untested" region do
not cross-over. When the results are analyzed based on those who were
known to test / not-test, much smaller mortality differences are
observed.

Those who argue against testing also ask, why has PCa mortality
dropped so quickly, can it really be due to PSA testing. For example
the Tyrol study really got underway in '93 when PSA testing was made
available for free to all Tyrollean men between the age 45-75. An
earlier update that I read studied the results from '93 to '01. The
midpoint of that study would be '97. If an untested man in the
adjacent canton would have been diagnosed in '97 had he been tested,
then being unaware of his PCa, it has remained untreated and
progressing for (now let me assume that your later reference stopped
data collection in 2005) 8 years. Not many men would die from PCa if
left untreated for 8 years. So why the rather immediate decline in PCa
deaths in the "tested" areas? If there is such a thing as "typical"
numbers, then a men who would have been diagnosed with early stage
disease (the most common variety found in regions with widespread
testing), but went undiagnosed because he wasn't tested might be
expected to live for 10-plus years. Why were PCa mortality statistics
dropping so much earlier in Tyrol?

Certainly fewer men are dying of advanced disease in the PSA era, but
at the cost of over-treatment (unecessary treatment [perhaps 20-40% of
men diagnosed] and reduced QOL for those treated). The PSA test is
not the culprit, but rather what one does with the information. As is
most often advocated, men should discuss the test with a doctor before
agreeing to the test. The aspects of over treatment and QOL should be
covered. Then the man should be honest with himself and decide if he
will make use of the information once he has it. This series of
events is unlikely to occur in a majority of cases.

PSA-testing is good for men who have PCa that needs treatment.
Unfortunately we don't always know who those men are after PSA
testing, after DRE and after biopsy...ron

On April 27, ron wrote:

> IMO, most of those who argue against wide spread PSA testing, don't
> argue from ignorance. Rather they ask, because of PSA testing how
> many men are needlessly treated, how does degraded QOL play into the
> equation. Further they argue that the results of the Tyrol and other
> similar studies are flawed.

Ah, "flawed." How, exactly?

And somehow I find it difficult to credit the idea that a man's QOL is
going to be degraded solely because he had a biopsy.

> The Tyrol experiment has been repeated in
> at least 3 other areas. The issue that all of these studies run into
> is that they must make assumptions about how many men in the "testing"
> region comply and how many men in the adjacent "untested" region do
> not cross-over. When the results are analyzed based on those who were
> known to test / not-test, much smaller mortality differences are
> observed.

Where would I find that information?

I will here repeat a part of the conclusion: "...there was a reduction
in prostate cancer mortality rates which was significantly greater than
the reduction in the rest of Austria." *In the rest of Austria*. So
where's the supposed cross-over?

> Those who argue against testing also ask, why has PCa mortality
> dropped so quickly, can it really be due to PSA testing. For example
> the Tyrol study really got underway in '93 when PSA testing was made
> available for free to all Tyrollean men between the age 45-75.

Yes: fifteen years ago. What is ron's point?

> Certainly fewer men are dying of advanced disease in the PSA era, but
> at the cost of over-treatment (unecessary treatment [perhaps 20-40% of
> men diagnosed] and reduced QOL for those treated).

See my question, above.

So the Wise Men say. And maybe some men are "over-treated." Is that a
reason or excuse for not testing anyone? I doubt it. It's just a cost of
excellent care.

> The PSA test is
> not the culprit, but rather what one does with the information.

Agreed.

> As is
> most often advocated, men should discuss the test with a doctor before
> agreeing to the test.

Preferably a medic who is well-trained in PCa matters, not one (like the
uro of a friend) who specializes in "female problems" for example.

> The aspects of over treatment and QOL should be
> covered.

Agreed. But bear in mind that it is more profitable to perform a
prostatectomy than to give advice. Yes indeed I do believe that that is
a factor.

> Then the man should be honest with himself and decide if he
> will make use of the information once he has it. This series of
> events is unlikely to occur in a majority of cases.

Possibly for the reason set forth above.

> PSA-testing is good for men who have PCa that needs treatment.
> Unfortunately we don't always know who those men are after PSA
> testing, after DRE and after biopsy

So the solution is.....?

Regards,

Steve J
Who does not believe that ignorance is bliss.

Steve...See my comments within your text...ron

On Apr 27, 5:25*pm, Steve Jordan <mycrofts...@cox.net> wrote:
> On April 27, ron wrote:
>
> > IMO, most of those who argue against wide spread PSA testing, don't
> > argue from ignorance. *Rather they ask, because of PSA testing how
> > many men are needlessly treated, how does degraded QOL play into the
> > equation. *Further they argue that the results of the Tyrol and other
> > similar studies are flawed. *
>
> Ah, "flawed." How, exactly?

cross-over problems and analysis based on assigned to test group/
presumed to test rather that actually tested/actually did not test

> And somehow I find it difficult to credit the idea that a man's QOL is
> going to be degraded solely because he had a biopsy.

Most men make decisions before understanding their disease, before
getting a complete diagnosis. A PSA test, a positive biopsy and off
to treatment. Unfortunate, but the real world.

> > The Tyrol experiment has been repeated in
> > at least 3 other areas. *The issue that all of these studies run into
> > is that they must make assumptions about how many men in the "testing"
> > region comply and how many men in the adjacent "untested" region do
> > not cross-over. *When the results are analyzed based on those who were
> > known to test / not-test, much smaller mortality differences are
> > observed.
>
> Where would I find that information?

Google for the Montreal analogue of the Tyrol study. Also the
following link has some information

http://www.medscape.com/viewarticle/545957?src=mp

> I will here repeat a part of the conclusion: "...there was a reduction
> in prostate cancer mortality rates which was significantly greater than
> the reduction in the rest of Austria." *In the rest of Austria*. So
> where's the supposed cross-over?

The men in Tyrol who did not test and the men in the rest of Austria
who did test.

> > Those who argue against testing also ask, why has PCa mortality
> > dropped so quickly, can it really be due to PSA testing. *For example
> > the Tyrol study really got underway in '93 when PSA testing was made
> > available for free to all Tyrollean men between the age 45-75. *
>
> Yes: fifteen years ago. What is ron's point?

Nowhere near 15 years. What is the time midpoint of the men covered
in the Tyrol study? 1997? When did the anaysis that you read
complete so that they could analyze the data, write a manuscript and
go through the review process? 2005?

That's 8 years elapsed. Not enough time for most men with early-stage
disease (the majority of what testing finds) to die. So why the large
reduction in mortality? Opponents argue the elapsed time is too short
for PSA testing to be the key factor in the observed mortality
reduction.

> > Certainly fewer men are dying of advanced disease in the PSA era, but
> > at the cost of over-treatment (unecessary treatment [perhaps 20-40% of
> > men diagnosed] and reduced QOL for those treated). *
>
> See my question, above.
>
> So the Wise Men say. And maybe some men are "over-treated." Is that a
> reason or excuse for not testing anyone? I doubt it. It's just a cost of
> excellent care.

Maybe some men? Probably 20-40%, I've read some estimates as high as
70-80%. That's a big cost of doing business.
>
> > The PSA test is
> > not the culprit, but rather what one does with the information. *
>
> Agreed.
>
> > As is
> > most often advocated, men should discuss the test with a doctor before
> > agreeing to the test. *
>
> Preferably a medic who is well-trained in PCa matters, not one (like the
> uro of a friend) who specializes in "female problems" for example.
>
> > The aspects of over treatment and QOL should be
> > covered. *
>
> Agreed. But bear in mind that it is more profitable to perform a
> prostatectomy than to give advice. Yes indeed I do believe that that is
> a factor.
>
> > Then the man should be honest with himself and decide if he
> > will make use of the information once he has it. *This series of
> > events is unlikely to occur in a majority of cases.
>
> Possibly for the reason set forth above.
>
> > PSA-testing is good for men who have PCa that needs treatment.
> > Unfortunately we don't always know who those men are after PSA
> > testing, after DRE and after biopsy
>
> So the solution is.....?

That's the problem, there is no solution available today.

> Regards,
>
> Steve J
> Who does not believe that ignorance is bliss.

Hello Ron,
Comments under RV>++++++++>
On Apr 27, 4:00*pm, ron <oit...@yahoo.com> wrote:
> IMO, most of those who argue against wide spread PSA testing, don't
> argue from ignorance. *Rather they ask, because of PSA testing how
> many men are needlessly treated, how does degraded QOL play into the
> equation. *Further they argue that the results of the Tyrol and other
> similar studies are flawed. *The Tyrol experiment has been repeated in
> at least 3 other areas. *The issue that all of these studies run into
> is that they must make assumptions about how many men in the "testing"
> region comply and how many men in the adjacent "untested" region do
> not cross-over. *When the results are analyzed based on those who were
> known to test / not-test, much smaller mortality differences are
> observed.
RV>+++++++++++++>
The "widespread" use of PSA testing even here in the USA is not as
widespread as reported. The "real" evidence suggests that in spite of
the expressed "widespread" use of PSA testing only 41% of men age 50
or above admit having a PSA within the last year. Men age 50 to 64 had
a worse score. Only 33.6% admitted to have a test within the last
year. In men 65 and above the figure is 51.3%. This alone is an
indication that the "modest" reduction in the mortality rate is not
that modest after all considering that the use of PSA is less common
than proclaimed.

Source: Swan J, Breen N, Coates RJ, Rimer BK, Lee NC. Progress in
cancer screening practices in the United States: results from the 2000
National Health Interview Survey. Cancer. 2003 Mar 15;97(6):1528-40.
PMID: 12627518 [PubMed - indexed for MEDLINE]

More recently the Cancer Prevention Fellowship Program, Division of
Cancer Prevention and Health Communication and Informatics Research
Branch, Division of Cancer Control and Population Science, National
Cancer Institute, Bethesda published that 44.8% of men ages 50 to 75
had never had a PSA test in their life. Hardly widespread use in my
view...and this fits the picture that we see at the support group
level with many men diagnosed with more advanced disease than they
should.

The Tyrol results can be reduced by crossover in the other provinces,
but isn't that a confirmation that early detection and treatment
affects disease-specific mortality? It is definitely a weak argument
against screening since mortality is reduced overall by screening.

The estimes of overtreatment have been greatly exaggerated. The Tyrol
study in which the mean age of screened men is <65 years, yielded a
8.7% overdiagnosis rate (according to the Epstein et al criteria).
This is a clinical result of a large population of men. Far more
accurate than exaggerated estimates created to detract from the value
of PSA testing by those opposed to PSA testing.

> Those who argue against testing also ask, why has PCa mortality
> dropped so quickly, can it really be due to PSA testing. *For example
> the Tyrol study really got underway in '93 when PSA testing was made
> available for free to all Tyrollean men between the age 45-75. *An
> earlier update that I read studied the results from '93 to '01. *The
> midpoint of that study would be '97. *If an untested man in the
> adjacent canton would have been diagnosed in '97 had he been tested,
> then being unaware of his PCa, it has remained untreated and
> progressing for (now let me assume that your later reference stopped
> data collection in 2005) 8 years. *Not many men would die from PCa if
> left untreated for 8 years. So why the rather immediate decline in PCa
> deaths in the "tested" areas? *If there is such a thing as "typical"
> numbers, then a men who would have been diagnosed with early stage
> disease (the most common variety found in regions with widespread
> testing), but went undiagnosed because he wasn't tested might be
> expected to live for 10-plus years. *Why were PCa mortality statistics
> dropping so much earlier in Tyrol?
RV>+++++++>
The answer to the earlier drop in mortality in Tyrol can very well be
explained by the early application of PSA testing and detection of a
pool of men with advanced cancers that when diagnosed and treated
responded to ADT. This is known to improve survival at that early
point of the study.

> Certainly fewer men are dying of advanced disease in the PSA era, but
> at the cost of over-treatment (unecessary treatment [perhaps 20-40% of
> men diagnosed] and reduced QOL for those treated). *The PSA test is
> not the culprit, but rather what one does with the information. *As is
> most often advocated, men should discuss the test with a doctor before
> agreeing to the test. *The aspects of over treatment and QOL should be
> covered. *Then the man should be honest with himself and decide if he
> will make use of the information once he has it. *This series of
> events is unlikely to occur in a majority of cases.
RV>++++++++>
As mentioned above, overtreatment estimates are exaggerated and the
deterioration of QOL caused by treatment( very real indeed) is never
compared by the deterioration of QOL by disease progression. What?
Disease progression can cause worse QOL? True, but never mentioned.
See, most PCa is indolent. We need these guys that find PSA so
ineffective to explain that to the nearly 30,000 men that die of PCa
here every year...

> PSA-testing is good for men who have PCa that needs treatment.
> Unfortunately we don't always know who those men are after PSA
> testing, after DRE and after biopsy...ron

Hi Ralph...My intent, when I first posted to this thread, was to make
clear that most of those who argue against PSA testing do so based on
data (data that has the same quirks and flaws as data from any other
non-controlled experiment) rather than ignorance. When I respond to
some of your points below, keep in mind that I am trying to discover
the truth by having a dialogue. I am not trying to defend their
position. There is a difference.

There are two points in your message that I would like to respond to.
You wrote...

> The Tyrol results can be reduced by crossover in the other provinces,
> but isn't that a confirmation that early detection and treatment
> affects disease-specific mortality? It is definitely a weak argument
> against screening since mortality is reduced overall by screening.

The Medscape link I posted above contains the following:
-------------------------------------------------------------------------------------------------
"it is disappointing that the authors of the current review found only
2 prospective trials of sufficient quality for evaluation. One study
randomized 46,193 men in Quebec to a prostate screening group or usual
care.[3] Screening was completed with a DRE and PSA, and the main
study outcome was prostate cancer at 11 years.

Although this trial demonstrated a 62% reduction in mortality related
to prostate cancer in the screening vs usual care groups, the current
review questions this result. The statistical analysis was not by
intention-to-screen (ie, data are evaluated for each individual
according to randomized assignment, regardless of whether he received
the screening intervention or not). The question of data analysis is a
significant issue in this trial in which only 23.6% of men randomized
to prostate cancer screening completed the screening protocol.
Moreover, 7.3% of subjects in the usual-care group received prostate
cancer screening. When the authors of the current review performed an
analysis of the study's data using the intention-to-screen principle,
the relative risk for death from prostate cancer in the screening
group relative to the usual care cohort was 1.01.

The other study evaluated in the review randomized men between the
ages of 50 and 69 in one Swedish town to prostate cancer screening or
usual care.[4] Compliance with screening was superior in this trial
compared with the Quebec study, although rates of crossover prostate
cancer screening in the usual-care group were unclear. The follow-up
period was 15 years, and data analysis was completed by the intention-
to-screen principle. While prostate cancer screening was associated
with a higher rate of finding all prostate cancer and, particularly,
localized tumors, the prostate-cancer-screening and usual-care groups
had similar rates of prostate cancer-specific survival and total
survival.

Combining data from the 2 studies resulted in a relative risk for
prostate cancer-specific death of 1.01 associated with prostate cancer
screening vs usual care. This result should make clinicians and
patients think twice about routine prostate cancer screening as
currently practiced, especially in light of what the Quebec and
Swedish studies failed to assess: quality-of-life data, costs of care,
and the overall potential harms of screening. These factors will have
to be weighed against the benefit of greater cancer detection rates at
earlier stages of prostate cancer."
-----------------------------------------------------------------------------------------------------

With only a 1.01 adjusted risk ratio for PCa mortality between the two
test groups, this analysis calls into question the claimed PCa
mortality advantage attendant screening. The analysis leading to the
"1.01" may well be in error. While I am unable to judge whether the
analysis is correct or incorrect, I have come across this point in
several different papers. I don't think that the different camps are
trying to mislead, rather I think these are honest scientific
differences of opinion around a difficult question.

The second point concerns overtreatment. You wrote...

> The estimes of overtreatment have been greatly exaggerated. The Tyrol
> study in which the mean age of screened men is <65 years, yielded a
> 8.7% overdiagnosis rate (according to the Epstein et al criteria).
> This is a clinical result of a large population of men. Far more
> accurate than exaggerated estimates created to detract from the value
> of PSA testing by those opposed to PSA testing.

As I stated earlier in the thread, I have seen estimates of
overtreatment ranging from 20 to 80%. Klotz, a highly respected
researcher has said, "At least two studies have attempted to model the
rate of diagnosing clinically insignificant disease, suggesting that
it ranges from 30% to 84%.4-5 The current incidence-to-mortality
ratio of about 7:1 suggests that the higher (84%) figure is more
likely." One of the early papers I came across that influenced my
thinking in this area was Moul's study (Journal of Clinical Oncology,
Vol 21, No 21 (November 1), 2003: pp 4001-4008) of 300+ men who chose
AS/WW as their first method of treatment. Moul follows these men as
they either stay with the AS/WW program or drop out to seek radical
intervention. He uses the standard K-M statistical analysis to
project the drop-out rate over time. He predicts that at 10 years,
20-25% of the men would remain in the AS/WW group; the rest having
gone on to seek radical treatment. It is important to note that the
men in Moul's study had PSA <20, GS<7, TNM<T3; considerably more
lenient than the Epstein criteria, so I view the 20-25% as a floor.

> As mentioned above, overtreatment estimates are exaggerated and the
> deterioration of QOL caused by treatment( very real indeed) is never
> compared by the deterioration of QOL by disease progression. What?
> Disease progression can cause worse QOL? True, but never mentioned.
> See, most PCa is indolent. We need these guys that find PSA so
> ineffective *to explain that to the nearly 30,000 men that die of PCa
> here every year...

Ralph, all I am saying is that because of PSA testing the pendulum has
swung from undertreatment to overtreatment. While I don't consider
myself to be in the anti-testing camp, I feel that they ask fair
questions and bring data to the conversation that seems to support
their position. Perhaps in a few years better controlled experiments
will tell us whether PSA testing saves lives or not. But even then
the core problem will not be solved. The real problem arises when we
realize that there is no happy or satisfactory middle ground available
today. Men should not die from PCa, nor should men be overtreated.
Better testing methodology is needed. We certainly have the means to
identify most men with PCa, but we can't always tell which of them
needs treatment...ron