Re: Finasteride and Intermittent ADT

[Guest guest]

Alan,

Interesting post. My question is: If you can extend your OFF time with

finasteride, do you really need to be doing something as draconian as ADT to

start with in the first place ?

Castration therapy 'lite' ala finasteride or dutasteride has been argued by Pat

Walsh to suppress the warning signs of progression. [Pat Walsh reference in 3.3

/ 3.4 articles on fitcare.org.uk ]

With just six men on this 'trial' it is just not statistically significant.

Besides, we don't know to what extent cherry picking has selected out 'non

responders' who did not get included in the final write-up.

One of the more sobering observations mentioned by Walsh from a Nordic study on

5alpha-reductase inhibitor treatment was that IF PSA started to rise from

'undetectable' there was a x3 fold increase in the risk of a fatal outcome due

to untreatable disease progression.

Caveat emptor.

Sam.

>

>

> The following study reports that men taking finasteride (Proscar)

> and engaging in intermittent ADT can get a much longer doubling

> time than those who don't take finasteride.

>

> http://www.urotoday.com/index.php?option=com_content & task=view_ua & id=2230310

>

> I don't know how generalizable the results are since only six men

> were studied, though it was over a period of 7-10 years. However

> the results were pretty dramatic, extending the doubling time

> from an average of 7.7 weeks to 45.1 weeks! Here's the

> conclusion of the abstract:

>

> Administration of finasteride was associated with a reduction

> in the rate of increase of serum PSA in the off-treatment

> period of any given cycle within a sequence of 5. In a total

> of 15 cycles, finasteride extended PSA doubling time from a

> mean of 7.7 weeks (n = 11, range 2.3-29.8 weeks) to a mean of

> 45.1 weeks (n = 6, range 13.8-99.7 weeks). One patient was

> characterized by an apparent pseudo-resistance to finasteride

> in the 2nd cycle of treatment and another patient by complete

> resistance to finasteride in the 4th cycle.

>

> Finasteride can be introduced into any cycle of intermittent

> androgen suppression with the expectation of an extension of

> PSA doubling time.

>

> Finasteride is a form of hormone therapy, so it's not surprising

> that it has an effect. But it is said to be one of the mildest

> forms of HT with fewer side effects than more potent drugs like

> Lupron or Casodex.

>

> As always with studies like these, we don't know if this

> translates to increased life extension, or just to lower PSA.

> But it's something to consider for those of us on intermittent

> ADT.

>

> If you start an ADT off period with a PSA of 0.1, and decide to

> get back when PSA >= 4.0, that's 5.32 doubling periods. Assuming

> the average response (and of course it differs from one man to

> another), the difference between 7.7 weeks per period

> and 45.1 weeks per period is:

>

> 5.32 * 7.7 = 41 weeks = 0.8 years time off

> 5.32 * 45.1 = 240 weeks = 4.6 years time off

>

> It looks like a big difference to me.

>

> Alan

>

[Guest guest]

I have all of the same questions and reservations that you do

Sammy. The study is intriguing, but for all of the reasons you

list, we don't really know what, if anything, we can conclude

from it.

Those of us who are on intermittent ADT (not myself, I'm not on

ADT at all now), can consult with their oncologists about this

and I'll be curious to hear any thoughts that the docs have. I'm

guessing that they'll have the same questions and reservations

too. The problem is that nobody knows enough about any of this

to arrive at firm conclusions.

Given the almost 6:1 increase in PSA doubling time, if I were on

intermittent ADT, and if my oncologist didn't have any strong

objections, I'd be strongly tempted to try finasteride or

dutasteride. I'd be gambling that either:

1) It would work. I'd get a longer time off ADT and some life

extension, or:

2) It wouldn't work, but would do no harm.

So much of life is a crap shoot. You close your eyes, make a

wish (or say a prayer if that's your inclination), and roll the

dice.

Alan

sammy_bates wrote:

> Alan,

>

> Interesting post. My question is: If you can extend your OFF

> time with finasteride, do you really need to be doing something

> as draconian as ADT to start with in the first place ?

>

> Castration therapy 'lite' ala finasteride or dutasteride has

> been argued by Pat Walsh to suppress the warning signs of

> progression. [Pat Walsh reference in 3.3 / 3.4 articles on

> fitcare.org.uk ]

>

> With just six men on this 'trial' it is just not statistically

> significant. Besides, we don't know to what extent cherry

> picking has selected out 'non responders' who did not get

> included in the final write-up.

>

> One of the more sobering observations mentioned by Walsh from a

> Nordic study on 5alpha-reductase inhibitor treatment was that

> IF PSA started to rise from 'undetectable' there was a x3 fold

> increase in the risk of a fatal outcome due to untreatable

> disease progression.

>

> Caveat emptor.

>

> Sam.

>

>

>

> >

> >

> > The following study reports that men taking finasteride

> > (Proscar) and engaging in intermittent ADT can get a much

> > longer doubling time than those who don't take finasteride.

> >

> > http://www.urotoday.com/index.php?option=com_content & task=view_ua & id=2230310

> >

> > I don't know how generalizable the results are since only six

> > men were studied, though it was over a period of 7-10 years.

> > However the results were pretty dramatic, extending the

> > doubling time from an average of 7.7 weeks to 45.1 weeks!

> > Here's the conclusion of the abstract:

> >

> > Administration of finasteride was associated with a

> > reduction in the rate of increase of serum PSA in the

> > off-treatment period of any given cycle within a sequence

> > of 5. In a total of 15 cycles, finasteride extended PSA

> > doubling time from a mean of 7.7 weeks (n = 11, range

> > 2.3-29.8 weeks) to a mean of 45.1 weeks (n = 6, range

> > 13.8-99.7 weeks). One patient was characterized by an

> > apparent pseudo-resistance to finasteride in the 2nd cycle

> > of treatment and another patient by complete resistance to

> > finasteride in the 4th cycle.

> >

> > Finasteride can be introduced into any cycle of

> > intermittent androgen suppression with the expectation of

> > an extension of PSA doubling time.

> >

> > Finasteride is a form of hormone therapy, so it's not

> > surprising that it has an effect. But it is said to be one

> > of the mildest forms of HT with fewer side effects than more

> > potent drugs like Lupron or Casodex.

> >

> > As always with studies like these, we don't know if this

> > translates to increased life extension, or just to lower PSA.

> > But it's something to consider for those of us on

> > intermittent ADT.

> >

> > If you start an ADT off period with a PSA of 0.1, and decide

> > to get back when PSA >= 4.0, that's 5.32 doubling periods.

> > Assuming the average response (and of course it differs from

> > one man to another), the difference between 7.7 weeks per

> > period and 45.1 weeks per period is:

> >

> > 5.32 * 7.7 = 41 weeks = 0.8 years time off 5.32 * 45.1 =

> > 240 weeks = 4.6 years time off

> >

> > It looks like a big difference to me.

> >

> > Alan

[Guest guest]

I have all of the same questions and reservations that you do

Sammy. The study is intriguing, but for all of the reasons you

list, we don't really know what, if anything, we can conclude

from it.

Those of us who are on intermittent ADT (not myself, I'm not on

ADT at all now), can consult with their oncologists about this

and I'll be curious to hear any thoughts that the docs have. I'm

guessing that they'll have the same questions and reservations

too. The problem is that nobody knows enough about any of this

to arrive at firm conclusions.

Given the almost 6:1 increase in PSA doubling time, if I were on

intermittent ADT, and if my oncologist didn't have any strong

objections, I'd be strongly tempted to try finasteride or

dutasteride. I'd be gambling that either:

1) It would work. I'd get a longer time off ADT and some life

extension, or:

2) It wouldn't work, but would do no harm.

So much of life is a crap shoot. You close your eyes, make a

wish (or say a prayer if that's your inclination), and roll the

dice.

Alan

sammy_bates wrote:

> Alan,

>

> Interesting post. My question is: If you can extend your OFF

> time with finasteride, do you really need to be doing something

> as draconian as ADT to start with in the first place ?

>

> Castration therapy 'lite' ala finasteride or dutasteride has

> been argued by Pat Walsh to suppress the warning signs of

> progression. [Pat Walsh reference in 3.3 / 3.4 articles on

> fitcare.org.uk ]

>

> With just six men on this 'trial' it is just not statistically

> significant. Besides, we don't know to what extent cherry

> picking has selected out 'non responders' who did not get

> included in the final write-up.

>

> One of the more sobering observations mentioned by Walsh from a

> Nordic study on 5alpha-reductase inhibitor treatment was that

> IF PSA started to rise from 'undetectable' there was a x3 fold

> increase in the risk of a fatal outcome due to untreatable

> disease progression.

>

> Caveat emptor.

>

> Sam.

>

>

>

> >

> >

> > The following study reports that men taking finasteride

> > (Proscar) and engaging in intermittent ADT can get a much

> > longer doubling time than those who don't take finasteride.

> >

> > http://www.urotoday.com/index.php?option=com_content & task=view_ua & id=2230310

> >

> > I don't know how generalizable the results are since only six

> > men were studied, though it was over a period of 7-10 years.

> > However the results were pretty dramatic, extending the

> > doubling time from an average of 7.7 weeks to 45.1 weeks!

> > Here's the conclusion of the abstract:

> >

> > Administration of finasteride was associated with a

> > reduction in the rate of increase of serum PSA in the

> > off-treatment period of any given cycle within a sequence

> > of 5. In a total of 15 cycles, finasteride extended PSA

> > doubling time from a mean of 7.7 weeks (n = 11, range

> > 2.3-29.8 weeks) to a mean of 45.1 weeks (n = 6, range

> > 13.8-99.7 weeks). One patient was characterized by an

> > apparent pseudo-resistance to finasteride in the 2nd cycle

> > of treatment and another patient by complete resistance to

> > finasteride in the 4th cycle.

> >

> > Finasteride can be introduced into any cycle of

> > intermittent androgen suppression with the expectation of

> > an extension of PSA doubling time.

> >

> > Finasteride is a form of hormone therapy, so it's not

> > surprising that it has an effect. But it is said to be one

> > of the mildest forms of HT with fewer side effects than more

> > potent drugs like Lupron or Casodex.

> >

> > As always with studies like these, we don't know if this

> > translates to increased life extension, or just to lower PSA.

> > But it's something to consider for those of us on

> > intermittent ADT.

> >

> > If you start an ADT off period with a PSA of 0.1, and decide

> > to get back when PSA >= 4.0, that's 5.32 doubling periods.

> > Assuming the average response (and of course it differs from

> > one man to another), the difference between 7.7 weeks per

> > period and 45.1 weeks per period is:

> >

> > 5.32 * 7.7 = 41 weeks = 0.8 years time off 5.32 * 45.1 =

> > 240 weeks = 4.6 years time off

> >

> > It looks like a big difference to me.

> >

> > Alan

[Guest guest]

sammy_bates wrote:

> Interesting post. My question is: If you can extend your OFF

> time with finasteride, do you really need to be doing something

> as draconian as ADT to start with in the first place ?

....

I didn't address this point in my other post. In the study, the

mean PSA doubling time for men not taking finasteride was 7.7

weeks. That strikes me as VERY aggressive. So I would think,

yes, these men really do need to be on ADT. Even the 45.1 week

PSA doubling time seems aggressive.

On the other hand however, I'm not sure we understand the nature

of PSA doubling time in the context of intermittent ADT. When a

man with cancer comes off ADT, his testosterone levels come back

slowly. When does one start measuring? And even when the T

level plateaus, is the doubling time relatively constant or does

it tend to slow over time or increase over time? Or is it

different for each particular cancer.

I suspect our knowledge of these doubling time issues is

incomplete even in the more common situations of pre-treatment

and post-treatment, not just the case of men with hormone

sensitive cancers who stop taking hormone suppressors.

Alan

[Guest guest]

sammy_bates wrote:

> Interesting post. My question is: If you can extend your OFF

> time with finasteride, do you really need to be doing something

> as draconian as ADT to start with in the first place ?

....

I didn't address this point in my other post. In the study, the

mean PSA doubling time for men not taking finasteride was 7.7

weeks. That strikes me as VERY aggressive. So I would think,

yes, these men really do need to be on ADT. Even the 45.1 week

PSA doubling time seems aggressive.

On the other hand however, I'm not sure we understand the nature

of PSA doubling time in the context of intermittent ADT. When a

man with cancer comes off ADT, his testosterone levels come back

slowly. When does one start measuring? And even when the T

level plateaus, is the doubling time relatively constant or does

it tend to slow over time or increase over time? Or is it

different for each particular cancer.

I suspect our knowledge of these doubling time issues is

incomplete even in the more common situations of pre-treatment

and post-treatment, not just the case of men with hormone

sensitive cancers who stop taking hormone suppressors.

Alan

[Guest guest]

Alan,

What prompted me to make that comment was my own repeated experience of ADT

followed by a rapid rise in PSA, followed by a near zero average PSADT. A PSA vs

Time graph has a 'dogs leg' or 'elbow'. Now if you use finasteride there is just

a steady rise in PSA from the usual nadir and no dogs leg. I discuss it in this

article:

http://fitcare.org.uk/epidemic/3.2.intermittent.hormone.therapy.html

What the relative risks of the two methods are I do not know. but I do know from

the PCPT / REDUCE trials that 5alpha-RI can hide true PSA values and in the case

of advanced disease increase risk of a fatal outcome. I quote another article

http://fitcare.org.uk/epidemic/4.2.chemoprevention.update.html

Note also appended some diagrams 3.2.x

Sam.

>

> > Interesting post. My question is: If you can extend your OFF

> > time with finasteride, do you really need to be doing something

> > as draconian as ADT to start with in the first place ?

> ...

>

> I didn't address this point in my other post. In the study, the

> mean PSA doubling time for men not taking finasteride was 7.7

> weeks. That strikes me as VERY aggressive. So I would think,

> yes, these men really do need to be on ADT. Even the 45.1 week

> PSA doubling time seems aggressive.

>

> On the other hand however, I'm not sure we understand the nature

> of PSA doubling time in the context of intermittent ADT. When a

> man with cancer comes off ADT, his testosterone levels come back

> slowly. When does one start measuring? And even when the T

> level plateaus, is the doubling time relatively constant or does

> it tend to slow over time or increase over time? Or is it

> different for each particular cancer.

>

> I suspect our knowledge of these doubling time issues is

> incomplete even in the more common situations of pre-treatment

> and post-treatment, not just the case of men with hormone

> sensitive cancers who stop taking hormone suppressors.

>

> Alan

>

[Guest guest]

Alan,

What prompted me to make that comment was my own repeated experience of ADT

followed by a rapid rise in PSA, followed by a near zero average PSADT. A PSA vs

Time graph has a 'dogs leg' or 'elbow'. Now if you use finasteride there is just

a steady rise in PSA from the usual nadir and no dogs leg. I discuss it in this

article:

http://fitcare.org.uk/epidemic/3.2.intermittent.hormone.therapy.html

What the relative risks of the two methods are I do not know. but I do know from

the PCPT / REDUCE trials that 5alpha-RI can hide true PSA values and in the case

of advanced disease increase risk of a fatal outcome. I quote another article

http://fitcare.org.uk/epidemic/4.2.chemoprevention.update.html

Note also appended some diagrams 3.2.x

Sam.

>

> > Interesting post. My question is: If you can extend your OFF

> > time with finasteride, do you really need to be doing something

> > as draconian as ADT to start with in the first place ?

> ...

>

> I didn't address this point in my other post. In the study, the

> mean PSA doubling time for men not taking finasteride was 7.7

> weeks. That strikes me as VERY aggressive. So I would think,

> yes, these men really do need to be on ADT. Even the 45.1 week

> PSA doubling time seems aggressive.

>

> On the other hand however, I'm not sure we understand the nature

> of PSA doubling time in the context of intermittent ADT. When a

> man with cancer comes off ADT, his testosterone levels come back

> slowly. When does one start measuring? And even when the T

> level plateaus, is the doubling time relatively constant or does

> it tend to slow over time or increase over time? Or is it

> different for each particular cancer.

>

> I suspect our knowledge of these doubling time issues is

> incomplete even in the more common situations of pre-treatment

> and post-treatment, not just the case of men with hormone

> sensitive cancers who stop taking hormone suppressors.

>

> Alan

>

[Guest guest]

On 7/10/10 Sam replied to Alan, in pertinent part:

> ... I do know from the PCPT / REDUCE trials that 5alpha-RI can hide true PSA

> values and in the case of advanced disease increase risk of a fatal

> outcome.

Sam is in error.

5-alpha reductase inhibitors, specifically finasteride, do not

" hide true PSA. "

When used for the label purpose of treating BPH, they reduce the

size of the prostate. That is their purpose. The reduction can be

as much as 50%. The less gland tissue, the lower the PSA. So the

manufacturers recommend doubling the PSA readings while the BPH

patient is on the med so as to have a better understanding of

his status as to development of PCa.

Once a patient is taking the 5-AR inhibitor as part of his tx for

_PCa_, the PSA readings are what they are and no adjustment is

necessary; in fact it would be misleading.

Here, from www.rxlist.com is what the manufacturer of finasteride

(Proscar) has to say:

" PROSCAR causes a decrease in serum PSA levels by approximately

50% in patients with BPH. This decrease is predictable over the

entire range of PSA values, although it may vary in individual

patients. Analysis of PSA data from over 3000 patients in PLESS

confirmed that in typical patients treated with PROSCAR for six

months or more, PSA values should be doubled for comparison with

normal ranges in untreated men. This adjustment preserves the

sensitivity and specificity of the PSA assay and maintains its

ability to detect prostate cancer.* PROSCAR may also cause

decreases in serum PSA in the presence of prostate cancer.

Any confirmed increases in PSA levels from nadir while on PROSCAR

may signal the presence of prostate cancer and should be

carefully evaluated, even if those values are still within the

normal range for men not taking a 5α-reductase inhibitor.

Non-compliance with PROSCAR therapy may also affect PSA test

results. "

*I should note an error: PSA does not " detect PCa. " Only the

biopsy does that.

Regards,

Steve J

[Guest guest]

On 7/10/10 Sam replied to Alan, in pertinent part:

> ... I do know from the PCPT / REDUCE trials that 5alpha-RI can hide true PSA

> values and in the case of advanced disease increase risk of a fatal

> outcome.

Sam is in error.

5-alpha reductase inhibitors, specifically finasteride, do not

" hide true PSA. "

When used for the label purpose of treating BPH, they reduce the

size of the prostate. That is their purpose. The reduction can be

as much as 50%. The less gland tissue, the lower the PSA. So the

manufacturers recommend doubling the PSA readings while the BPH

patient is on the med so as to have a better understanding of

his status as to development of PCa.

Once a patient is taking the 5-AR inhibitor as part of his tx for

_PCa_, the PSA readings are what they are and no adjustment is

necessary; in fact it would be misleading.

Here, from www.rxlist.com is what the manufacturer of finasteride

(Proscar) has to say:

" PROSCAR causes a decrease in serum PSA levels by approximately

50% in patients with BPH. This decrease is predictable over the

entire range of PSA values, although it may vary in individual

patients. Analysis of PSA data from over 3000 patients in PLESS

confirmed that in typical patients treated with PROSCAR for six

months or more, PSA values should be doubled for comparison with

normal ranges in untreated men. This adjustment preserves the

sensitivity and specificity of the PSA assay and maintains its

ability to detect prostate cancer.* PROSCAR may also cause

decreases in serum PSA in the presence of prostate cancer.

Any confirmed increases in PSA levels from nadir while on PROSCAR

may signal the presence of prostate cancer and should be

carefully evaluated, even if those values are still within the

normal range for men not taking a 5α-reductase inhibitor.

Non-compliance with PROSCAR therapy may also affect PSA test

results. "

*I should note an error: PSA does not " detect PCa. " Only the

biopsy does that.

Regards,

Steve J

[Guest guest]

Steve,

I’m a bit confused by your post. You say:

<snip> Once a patient is taking the 5-AR inhibitor as part of his tx for PCa_,

the PSA readings are what they are and no adjustment is necessary; in fact it

would be misleading. <snip>

But the Proscar information is <snip>

PROSCAR may also cause decreases in serum PSA in the presence

of prostate cancer. <snip>

Does that not mean that some adjustment is

necessary to have like for like comparisons? Perhaps you could clarify this?

I also think that it is important to note

two qualifiers in the Proscar information:

 <snip> PROSCAR causes a decrease in

serum PSA levels by approximately 50% in patients with BPH. <snip>  Not

the ‘approximate’ – clearly it is not precisely 50%, so it must therefore be equally

incorrect to merely double the PSA result, since some men might, for example

only have a 20% reduction in their gland volume and doubling their PSA number

would be misleading.

<snip>  This decrease is predictable

over the entire range of PSA values, although it may vary in individual patients.

<snip>  Again, highlighting the fact that broad statistics, especially

from a retrospective fairly small population cannot and should not be applied willy-nilly

to individuals

All the best

Prostate men need enlightening, not

frightening

Terry Herbert - diagnosed in 1996 and

still going strong

Read A Strange Place for unbiased information at http://www.yananow.net/StrangePlace/index.html

From: ProstateCancerSupport [mailto:ProstateCancerSupport ] On Behalf Of Steve Jordan

Sent: Sunday, 11 July 2010 7:11 AM

To: ProstateCancerSupport

Subject: Re:

Re: Finasteride and Intermittent ADT

On 7/10/10 Sam replied to Alan, in pertinent part:

> ... I do know from the PCPT / REDUCE trials that 5alpha-RI can hide true

PSA

> values and in the case of advanced disease increase risk of a fatal

> outcome.

Sam is in error.

5-alpha reductase inhibitors, specifically finasteride, do not

" hide true PSA. "

When used for the label purpose of treating BPH, they reduce the

size of the prostate. That is their purpose. The reduction can be

as much as 50%. The less gland tissue, the lower the PSA. So the

manufacturers recommend doubling the PSA readings while the BPH

patient is on the med so as to have a better understanding of

his status as to development of PCa.

Once a patient is taking the 5-AR inhibitor as part of his tx for

_PCa_, the PSA readings are what they are and no adjustment is

necessary; in fact it would be misleading.

Here, from www.rxlist.com is what the manufacturer of finasteride

(Proscar) has to say:

" PROSCAR causes a decrease in serum PSA levels by approximately

50% in patients with BPH. This decrease is predictable over the

entire range of PSA values, although it may vary in individual

patients. Analysis of PSA data from over 3000 patients in PLESS

confirmed that in typical patients treated with PROSCAR for six

months or more, PSA values should be doubled for comparison with

normal ranges in untreated men. This adjustment preserves the

sensitivity and specificity of the PSA assay and maintains its

ability to detect prostate cancer.* PROSCAR may also cause

decreases in serum PSA in the presence of prostate cancer.

Any confirmed increases in PSA levels from nadir while on PROSCAR

may signal the presence of prostate cancer and should be

carefully evaluated, even if those values are still within the

normal range for men not taking a 5á-reductase inhibitor.

Non-compliance with PROSCAR therapy may also affect PSA test

results. "

*I should note an error: PSA does not " detect PCa. " Only the

biopsy does that.

Regards,

Steve J

[Guest guest]

Steve,

I’m a bit confused by your post. You say:

<snip> Once a patient is taking the 5-AR inhibitor as part of his tx for PCa_,

the PSA readings are what they are and no adjustment is necessary; in fact it

would be misleading. <snip>

But the Proscar information is <snip>

PROSCAR may also cause decreases in serum PSA in the presence

of prostate cancer. <snip>

Does that not mean that some adjustment is

necessary to have like for like comparisons? Perhaps you could clarify this?

I also think that it is important to note

two qualifiers in the Proscar information:

 <snip> PROSCAR causes a decrease in

serum PSA levels by approximately 50% in patients with BPH. <snip>  Not

the ‘approximate’ – clearly it is not precisely 50%, so it must therefore be equally

incorrect to merely double the PSA result, since some men might, for example

only have a 20% reduction in their gland volume and doubling their PSA number

would be misleading.

<snip>  This decrease is predictable

over the entire range of PSA values, although it may vary in individual patients.

<snip>  Again, highlighting the fact that broad statistics, especially

from a retrospective fairly small population cannot and should not be applied willy-nilly

to individuals

All the best

Prostate men need enlightening, not

frightening

Terry Herbert - diagnosed in 1996 and

still going strong

Read A Strange Place for unbiased information at http://www.yananow.net/StrangePlace/index.html

From: ProstateCancerSupport [mailto:ProstateCancerSupport ] On Behalf Of Steve Jordan

Sent: Sunday, 11 July 2010 7:11 AM

To: ProstateCancerSupport

Subject: Re:

Re: Finasteride and Intermittent ADT

On 7/10/10 Sam replied to Alan, in pertinent part:

> ... I do know from the PCPT / REDUCE trials that 5alpha-RI can hide true

PSA

> values and in the case of advanced disease increase risk of a fatal

> outcome.

Sam is in error.

5-alpha reductase inhibitors, specifically finasteride, do not

" hide true PSA. "

When used for the label purpose of treating BPH, they reduce the

size of the prostate. That is their purpose. The reduction can be

as much as 50%. The less gland tissue, the lower the PSA. So the

manufacturers recommend doubling the PSA readings while the BPH

patient is on the med so as to have a better understanding of

his status as to development of PCa.

Once a patient is taking the 5-AR inhibitor as part of his tx for

_PCa_, the PSA readings are what they are and no adjustment is

necessary; in fact it would be misleading.

Here, from www.rxlist.com is what the manufacturer of finasteride

(Proscar) has to say:

" PROSCAR causes a decrease in serum PSA levels by approximately

50% in patients with BPH. This decrease is predictable over the

entire range of PSA values, although it may vary in individual

patients. Analysis of PSA data from over 3000 patients in PLESS

confirmed that in typical patients treated with PROSCAR for six

months or more, PSA values should be doubled for comparison with

normal ranges in untreated men. This adjustment preserves the

sensitivity and specificity of the PSA assay and maintains its

ability to detect prostate cancer.* PROSCAR may also cause

decreases in serum PSA in the presence of prostate cancer.

Any confirmed increases in PSA levels from nadir while on PROSCAR

may signal the presence of prostate cancer and should be

carefully evaluated, even if those values are still within the

normal range for men not taking a 5á-reductase inhibitor.

Non-compliance with PROSCAR therapy may also affect PSA test

results. "

*I should note an error: PSA does not " detect PCa. " Only the

biopsy does that.

Regards,

Steve J

[Guest guest]

> I’m a bit confused by your post. You say:

>

> <snip> Once a patient is taking the 5-AR inhibitor as part of his tx for

> PCa_, the PSA readings are what they are and no adjustment is necessary;

> in fact it would be misleading. <snip>

>

> But the Proscar information is <snip> PROSCAR may also cause decreases

> in serum PSA in the presence of prostate cancer. <snip>

Ah, but that might occur in the absence of a dx of PCa.

I'm no more a medic than Terry is, but, knowing what I know (a

bit more than I knew seven years ago) I would recommend that a

BPH patient on Proscar or Avodart might find it prudent,

especially if he is at enhanced risk such as a family hx, to

check other markers from time to time. Prostatic acid phosphatase

could provide a heads-up, for example.

BTW, how is it going with the Gleason 10 bloke? Let me know, if

you will, via e-mail.

Regards,

Steve J

[Guest guest]

Well Steve, if I am in error, then so is Pat Walsh who wrote an editorial in the NEJM covering the latest REDUCE report.

In

the April 2010 issue of the New England Journal of Medicine a report

on the REDUCE Trial for prostate cancer chemoprevention claimed that

dutasteride did indeed protect against prostate cancer in the male

populationi.

However, one of the journal editors, the well known urologist

Walsh argued the REDUCE Trial showed no evidence of dutasteride

preventing prostate cancer. Walsh maintained that like its

predecessor finasteride, dutasteride merely masks the disease (i.e auppresses tru PSA), thus

increasing the risk that more advanced disease will be detected later

making it more difficult to treatii.

Sam.

i

Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M,

Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ,

Somerville MC, TH, Fowler IL, Rittmaster RS; REDUCE Study

Group. Effect of dutasteride on the risk of prostate cancer. N

Engl J Med. 2010 Apr 1;362(13):1192-202. PubMed PMID: 20357281.

ii

Walsh PC. Chemoprevention of prostate cancer. N Engl J Med.

2010 Apr 1;362(13):1237-8. PubMed PMID: 20357287

>> On 7/10/10 Sam replied to Alan, in pertinent part:> > > ... I do know from the PCPT / REDUCE trials that 5alpha-RI can hide true PSA> > values and in the case of advanced disease increase risk of a fatal> > outcome.> > Sam is in error.> > 5-alpha reductase inhibitors, specifically finasteride, do not > "hide true PSA."> > When used for the label purpose of treating BPH, they reduce the > size of the prostate. That is their purpose. The reduction can be > as much as 50%. The less gland tissue, the lower the PSA. So the > manufacturers recommend doubling the PSA readings while the BPH > patient is on the med so as to have a better understanding of > his status as to development of PCa.> > Once a patient is taking the 5-AR inhibitor as part of his tx for > _PCa_, the PSA readings are what they are and no adjustment is > necessary; in fact it would be misleading.> > Here, from www.rxlist.com is what the manufacturer of finasteride > (Proscar) has to say:> > "PROSCAR causes a decrease in serum PSA levels by approximately > 50% in patients with BPH. This decrease is predictable over the > entire range of PSA values, although it may vary in individual > patients. Analysis of PSA data from over 3000 patients in PLESS > confirmed that in typical patients treated with PROSCAR for six > months or more, PSA values should be doubled for comparison with > normal ranges in untreated men. This adjustment preserves the > sensitivity and specificity of the PSA assay and maintains its > ability to detect prostate cancer.* PROSCAR may also cause > decreases in serum PSA in the presence of prostate cancer.> > Any confirmed increases in PSA levels from nadir while on PROSCAR > may signal the presence of prostate cancer and should be > carefully evaluated, even if those values are still within the > normal range for men not taking a 5α-reductase inhibitor. > Non-compliance with PROSCAR therapy may also affect PSA test > results."> > *I should note an error: PSA does not "detect PCa." Only the > biopsy does that.> > Regards,> > Steve J>

[Guest guest]

On 7/11/10 Sam replied to me:

> Well Steve, if I am in error, then so is Pat Walsh who wrote an

> editorial in the NEJM covering the latest REDUCE report.

Good company.

> In the April 2010 issue of the New England Journal of Medicine a report

> on the REDUCE Trial for prostate cancer chemoprevention claimed that

> dutasteride did indeed protect against prostate cancer in the male

> population.

I assume that Sam refers to the Andriole et al. article, " Effect

of dutasteride on the risk of prostate cancer. "

> However, one of the journal editors, the

> well known urologist Walsh argued the REDUCE Trial showed no

> evidence of dutasteride preventing prostate cancer.

What Walsh actually wrote is, " ...the reduction in the rate

of incident cancer was limited to the incidence

of prostate tumors with Gleason scores of 5 to 6,

which are moderately well differentiated; there

was no significant reduction in the incidence of

tumors that were less differentiated (Gleason

scores of 7 to 10) — tumors that are more likely

to be lethal. "

Well, the lower-grade tumors very well might develop into

high-grade tumors, " which are more likely to be lethal. "

> Walsh maintained

> that like its predecessor finasteride, dutasteride merely masks the

> disease (i.e auppresses tru PSA), thus increasing the risk that more

> advanced disease will be detected /later/ making it more difficult to

> treat.

What Walsh actually wrote is, " Because PSA levels are suppressed,

men may

have a false sense of security, and if prostate cancer ever

develops, the diagnosis may be delayed until they have high-grade

disease that may be difficult

to cure. "

That's why the manufacturers recommend an adjustment of PSA

results by men who are using the meds for tx of BPH. Presumably,

if a man is taking the med for prevention purposes he would

perform the same adjustment.

Walsh's use of the word, " suppressed " is as unfortunate as it is

misleading. There is no " true PSA " that is by some mysterious

biological process hidden from detection by 5-AR inhibitors.

Please read the quote in my previous post from the finasteride

label information.

What we have here is a difference of opinion between Andriole et

al. and Walsh. As Sam surely must have noted, in PCa as well as

other aspects of medicine, hardly anyone agrees with anyone else.

Regards,

Steve J

" The price of freedom from prostate cancer is eternal vigilance. "

--paraphrasing Jefferson

[Guest guest]

Steve,

It is comforting to know you are not only correcting me, but Walsh as well ;-)

Sam.

>

> On 7/11/10 Sam replied to me:

>

> > Well Steve, if I am in error, then so is Pat Walsh who wrote an

> > editorial in the NEJM covering the latest REDUCE report.

>

> Good company.

>

> > In the April 2010 issue of the New England Journal of Medicine a report

> > on the REDUCE Trial for prostate cancer chemoprevention claimed that

> > dutasteride did indeed protect against prostate cancer in the male

> > population.

>

> I assume that Sam refers to the Andriole et al. article, " Effect

> of dutasteride on the risk of prostate cancer. "

>

> > However, one of the journal editors, the

> > well known urologist Walsh argued the REDUCE Trial showed no

> > evidence of dutasteride preventing prostate cancer.

>

> What Walsh actually wrote is, " ...the reduction in the rate

> of incident cancer was limited to the incidence

> of prostate tumors with Gleason scores of 5 to 6,

> which are moderately well differentiated; there

> was no significant reduction in the incidence of

> tumors that were less differentiated (Gleason

> scores of 7 to 10) — tumors that are more likely

> to be lethal. "

>

> Well, the lower-grade tumors very well might develop into

> high-grade tumors, " which are more likely to be lethal. "

>

> > Walsh maintained

> > that like its predecessor finasteride, dutasteride merely masks the

> > disease (i.e auppresses tru PSA), thus increasing the risk that more

> > advanced disease will be detected /later/ making it more difficult to

> > treat.

>

> What Walsh actually wrote is, " Because PSA levels are suppressed,

> men may

> have a false sense of security, and if prostate cancer ever

> develops, the diagnosis may be delayed until they have high-grade

> disease that may be difficult

> to cure. "

>

> That's why the manufacturers recommend an adjustment of PSA

> results by men who are using the meds for tx of BPH. Presumably,

> if a man is taking the med for prevention purposes he would

> perform the same adjustment.

>

> Walsh's use of the word, " suppressed " is as unfortunate as it is

> misleading. There is no " true PSA " that is by some mysterious

> biological process hidden from detection by 5-AR inhibitors.

> Please read the quote in my previous post from the finasteride

> label information.

>

> What we have here is a difference of opinion between Andriole et

> al. and Walsh. As Sam surely must have noted, in PCa as well as

> other aspects of medicine, hardly anyone agrees with anyone else.

>

> Regards,

>

> Steve J

>

> " The price of freedom from prostate cancer is eternal vigilance. "

> --paraphrasing Jefferson

>

[Guest guest]

On 7/11/10 Sam replied to me:

> Steve,

>

> It is comforting to know you are not only correcting me, but Walsh as

> well ;-)

At your service, sir.

Regards,

Steve J

" 'MD' does not mean 'Medical Deity.' "

-- B. Strum, MD

Medical Oncologist

PCa Specialist

[Guest guest]

Guys you keep debating because you educating me about my disease and making I know a little about what is and will happen to me. Keep it up!

Tom W.

To: ProstateCancerSupport Sent: Mon, July 12, 2010 8:34:48 AMSubject: Re: Re: Finasteride and Intermittent ADT

On 7/11/10 Sam replied to me:> Steve,>> It is comforting to know you are not only correcting me, but Walsh as> well ;-)At your service, sir.Regards,Steve J"'MD' does not mean 'Medical Deity.'"-- B. Strum, MDMedical OncologistPCa Specialist

[Guest guest]

I'm inclined to think that all of the posters have some right on

their sides in different ways in the discussion of PSA and

finasteride / dutasteride.

Steve is certainly right in saying that the PSA is what it is, no

PSA is " masked " if that means present but undetected. The drugs

reduce the amount of PSA expressed by the prostate cells.

However I think what Sammy and Terry meant to say was that a 50%

reduction in PSA brought about by the drugs does not prove that

there is a corresponding 50% reduction in the quantity of cancer

in the body. The statement by the drug manufacturer is a warning

to that effect. The manufacturer suggests that, for the purpose

of determining whether and how much cancer may be present, double

the PSA value while taking the drug.

There also appears to be a disagreement about the meaning of Dr.

Walsh's remarks.

I think there are two different cases here:

Case 1: A man who has not had a biopsy, is not known to have

cancer, but has an elevated PSA.

In that case, a reduction in PSA brought about by the

drugs can mislead the patient and his doctor into

thinking there is no cancer, hence he might delay

diagnosis and treatment, at some danger to his life.

Case 2: A man is known to have cancer. He has already failed

primary treatment, or was determined to be a poor

candidate for primary treatment, and is now on ADT and

has chosen to take an ADT holiday, i.e., intermittent

therapy.

For that man, there really isn't much to " mask " , and may

be very little to risk. He already knows he has cancer.

There are no treatment options for him except ADT,

followed by more toxic treatments that are currently not

prescribed unless and until ADT fails. At worst, a low

PSA reading might lead him to delay a return to more

aggressive ADT longer than he should have - though Dr.

Walsh believes that, in general, one should delay ADT as

long as practicable anyway (though I think most medical

oncologists now disagree with that).

It seems to me that for a man in the case 2 situation, the main

reason for not trying the 5-AR inhibitors would be a belief that

they will make the cancer worse. I'm not aware of any evidence

that they will, though I don't know for sure that they don't.

Ed Friedman, an academic who studies the molecular biology of

PCa, posted the following about using finasteride this way in

alt.support.cancer.prostate:

" I may be pointing out the obvious here, but this is pretty

much the protocol that Dr. Leibowitz has been using for

around 10 years now for his patients. "

So there is some experience with this approach.

For myself, if I were attempting intermittent ADT, I think I

would discuss it with my oncologist and do as much research as I

could. However, assuming I learned nothing else and just based

on the little I know now, not much to be sure, I'd be inclined to

try one of the 5-alpha reductase inhibitors. My hopes would be:

1. It would prolong my ADT off period.

2. It would extend my life.

3. If it didn't do either of those things, at least it wouldn't

make anything worse.

But like everything else, it's a crap shoot. We don't know for

sure that any of the above 3 wishes would come true.

Alan

[Guest guest]

Alan & All -- there are a couple of ** inline comments **. Please see below. Sam.>> I'm inclined to think that all of the posters have some right on> their sides in different ways in the discussion of PSA and> finasteride / dutasteride.> > Steve is certainly right in saying that the PSA is what it is, no> PSA is "masked" if that means present but undetected. The drugs> reduce the amount of PSA expressed by the prostate cells.** I agree with that. Is that what Steve was saying ? > > However I think what Sammy and Terry meant to say was that a 50%> reduction in PSA brought about by the drugs does not prove that> there is a corresponding 50% reduction in the quantity of cancer> in the body. The statement by the drug manufacturer is a warning> to that effect. The manufacturer suggests that, for the purpose> of determining whether and how much cancer may be present, double> the PSA value while taking the drug.> > There also appears to be a disagreement about the meaning of Dr.> Walsh's remarks.> > I think there are two different cases here:> > Case 1: A man who has not had a biopsy, is not known to have> cancer, but has an elevated PSA.> > In that case, a reduction in PSA brought about by the> drugs can mislead the patient and his doctor into> thinking there is no cancer, hence he might delay> diagnosis and treatment, at some danger to his life.> > Case 2: A man is known to have cancer. He has already failed> primary treatment, or was determined to be a poor> candidate for primary treatment, and is now on ADT and> has chosen to take an ADT holiday, i.e., intermittent> therapy.> > For that man, there really isn't much to "mask", and may> be very little to risk. He already knows he has cancer.> There are no treatment options for him except ADT,> followed by more toxic treatments that are currently not> prescribed unless and until ADT fails. At worst, a low> PSA reading might lead him to delay a return to more> aggressive ADT longer than he should have - though Dr.> Walsh believes that, in general, one should delay ADT as> long as practicable anyway (though I think most medical> oncologists now disagree with that). ** It depends on the stage surely. WW and Active surveillance are recommended options in various PC guidlines. Patient choices are also recommended because of the generally recognised fact that ADT does not do an awful lot of good in the long run. See paragraphs 9-12 in article:http://fitcare.org.uk/epidemic/3.1.dog's.life.html > > It seems to me that for a man in the case 2 situation, the main> reason for not trying the 5-AR inhibitors would be a belief that> they will make the cancer worse. I'm not aware of any evidence> that they will, though I don't know for sure that they don't.** Evidence is available see article:http://fitcare.org.uk/epidemic/4.1.chemoprevention.warning.htmlTarle M, Spajic B, Kraljic I, Kusic Z. Continuous

finasteride

therapy for benign prostate hypertrophy upgrades both neuroendorcine

differentiation and aggressive prostate cancer. Anticancer Res.

2009 May;29(5):1797-801. PubMed:19443407** ANDhttp://fitcare.org.uk/epidemic/4.2.chemoprevention.update.htmlCote RJ, Skinner EC, Salem CE, Mertes SJ,

Stanczyk FZ, BE,

Pike MC, Ross RK. The effect of finasteride on the prostate

gland in men with elevated serum prostate-specific antigen levels.

Br J Cancer. 1998 Aug;78(3):413-8. PubMed:9703292> > Ed Friedman, an academic who studies the molecular biology of> PCa, posted the following about using finasteride this way in> alt.support.cancer.prostate:> > "I may be pointing out the obvious here, but this is pretty> much the protocol that Dr. Leibowitz has been using for> around 10 years now for his patients."> > So there is some experience with this approach.** As I recall Leibowitz is giving his patients up to x2 to top of the male range exogenous androgen on his TRT protocol. On top of that he gives 5 -10 mg finasteride. As far as I am aware he has never quoted (measured) DHT levels in his patients on TRT. A bit of an oversight really.In that scenario, I don't know how much blocking of T there is to DHT. Not much I would expect. I would expect the presence of finasteride (castration 'lite') a sop perhaps to the 'finasteride huggers' and the castration cowboy mentality that still dominates PC science / medicine.S> > > For myself, if I were attempting intermittent ADT, I think I> would discuss it with my oncologist and do as much research as I> could. However, assuming I learned nothing else and just based> on the little I know now, not much to be sure, I'd be inclined to> try one of the 5-alpha reductase inhibitors. My hopes would be:> > 1. It would prolong my ADT off period.> > 2. It would extend my life.> > 3. If it didn't do either of those things, at least it wouldn't> make anything worse.> > But like everything else, it's a crap shoot. We don't know for> sure that any of the above 3 wishes would come true.> > Alan>

[Guest guest]

(snip)

>

> The drugs reduce the amount of PSA expressed by the prostate cells.

(snip)

Just a bit of a correction. The 5-alpha reductase inhibitors

reduce the number of prostate cells, thus reducing the size of

the prostate. That is their " label " purpose.

The fewer cell, the less PSA. I believe that the remaining cells

are still busy pumping out PSA in the same amount as before.

This may be a distinction without a difference.

>

> However I think what Sammy and Terry meant to say was that a 50%

> reduction in PSA brought about by the drugs does not prove that

> there is a corresponding 50% reduction in the quantity of cancer

> in the body.

Certainly true.

(snip)

Regards,

Steve J

[Guest guest]

Well, Sammy hasn't totally convinced me yet, but he's certainly

planted some doubts in my mind concerning the efficacy of

finasteride during ADT off periods.

Research on all these issues proceeds very slowly. I have no

doubt that the primary reason is that it's just very, very hard.

The events of interest inside a cancerous cell take place inside

a living body and on a submicroscopic scale. You can't watch

them. You can't poke around inside the cell to see what's

happening without killing the cell (never mind the patient) and

keeping anything from happening. You can't easily distinguish

the molecules of interest, which may make up .0001% or even much

less of the total contents of the cell.

So what we get are statistical studies. Take this drug for

three months and measure PSA. Then make some by guess and by

gosh speculations about what actually happened. It's pretty

astounding that there's any progress at all. My hat is off to

those scientists who actually succeed in figuring anything out.

For myself, I'm not on ADT and not on intermittent ADT. I don't

have to worry about this issue or make any choices. For those of

you who are on ADT and/or intermittent ADT, I don't have any

advice. What can I say except what I always say to everyone with

cancer?

Best of luck.

Alan