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Old 10-16-2009, 08:02 PM   #1
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chemoprevention of prostate cancer

I have been interested recently in the subject of chemoprevention of prostate cancer using finasteride or dutasteride. As has been discussed elsewhere on this board, there was initially a concern that, while these drugs appear materially to reduce the risk of prostate cancer, they may cause higher grade tumors when prostate cancer does arise. More recent research seems to suggest that these drugs do not create higher grade tumors (but perhaps instead that they simply make those tumors easier to detect). This all seems to make taking one of these drugs attractive for someone at high risk of prostate cancer, particularly since the side effect profile is not so bad. However, I recently read a letter by Dr. Walsh at JHU recommending against using these drugs for chemoprevention, and subsequently heard a lecture by his colleague Dr. Carter, who also recommended against taking finasteride for chemoprevention purposes. And then I read an article by Dr. Catalona also recommending against this "off label" use of finasteride or dutasteride. (I would post links to these articles, but I am not sure I am permitted to do so by this board's posting policy). So it seems that some "heavy hitters" are lining up against this approach, despite the recent resarch.

Does anyone know of a well-respected prostate cancer expert who is recommending the use of 5 alpha-reductase inhibitors for chemoprevention purposes in high risk individuals who do not otherwise need these drugs (in other words, who do not have BPH)? I am not looking for a doc who will prescribe it -- there are plenty of those -- just trying to see where the "true experts" stand on this issue.

 
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Old 10-17-2009, 04:14 PM   #2
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Re: chemoprevention of prostate cancer

Hi medved,

I hope I can help resolve the confusion caused by negative comments from Dr. Walsh and others. I'll respond in green to key excerpts of your post. To start out, here is what struck you:


Quote:
Originally Posted by medved View Post
I have been interested recently in the subject of chemoprevention of prostate cancer using finasteride or dutasteride. ... However, I recently read a letter by Dr. Walsh at JHU recommending against using these drugs for chemoprevention, and subsequently heard a lecture by his colleague Dr. Carter, who also recommended against taking finasteride for chemoprevention purposes. And then I read an article by Dr. Catalona also recommending against this "off label" use of finasteride or dutasteride. ... So it seems that some "heavy hitters" are lining up against this approach, despite the recent resarch.

I was not aware of Dr. Walsh's stand on finasteride (and Avodart) for prevention, but I did find a letter from him about it. The letter is in the July 10, 2009 Journal of Clinical Oncology (the main journal for medical oncologists and their association ASCO - the American Society for Clinical Oncology) (Vol. 27, Number 20); it's entitled "Three Considerations Before Advising 5-[alpha, title actually uses the Greek letter alpha]-Reductase Inhibitors [5-ARIs for short] for Chemoprevention." I also found some abstracts of papers involving Drs. Catalona and Carter and finasteride, but they did not appear to be relevant, so I'll keep looking. Of course, all three doctors are major figures in American urological surgery for prostate cancer, and Dr. H. Ballentine Carter also heads the Johns Hopkins active surveillance program. Dr. Walsh makes three negative points, and I'll address them. My bottom line: I think he's not looking at the issue and data from a good vantage point, causing him to miss the benefits and see negative points that are not there. I think that's pretty clear, and I suspect his letter will get quite a response on the other side from his medical colleagues.

His first point: "First, 5-ARIs do not prevent prostate cancer, they just prevent men from undergoing diagnostic biopsies. Because 5-ARIs reduce prostate specific antigen (PSA) levels by at least 50%, patients and their physicians can be lulled into a false sense of security...." He presents several points in support. First he notes that "although 25% fewer men on finasteride were diagnosed with prostate cancer, this occurred largely because 15% fewer men underwent a diagnostic biopsy." He follows this with the observation that finasteride reduced the risk of a positive biopsy, for those who had biopsies, by only 10%, then disregards the earlier 15% reduction (those who did not need a biopsy) and observes that the 10% difference by itself was not statistically significant.

Well, why is it sound to disregard the 15% fewer men needing a biopsy? It isn't! That fifteen percent is part of the evidence for prevention! I'm confident the experts on finasteride will point out that that 15% is made up of men where finasteride was preventing cancer and who did not have prostate infections, inflammations, perhaps a minor contribution from BPH (since finasteride shrinks prostates - it's approved for BPH) or other non-cancerous triggers for a biopsy. Therefore, the 15% and 10% deserve to be added, and the combined reduction is statistically significant. By the way, Dr. Ian Fleming, leader of the finasteride trial (The Prostate Cancer Prevent Trial, known as PCPT), and colleagues now believe, on more detailed analysis of the trial data, that the prevention percentage is probably about 30%, somewhat higher than the earlier estimate. Also, there's more to rebut about that 10% lower figure for biopsies tied to his second point.

His second point: his second is a concern that men on finasteride will be lulled into not having biopsies because finasteride cuts the PSA level by about 50%, as he mentions earlier.

The rebuttal to that is simple: doctors (and hopefully patients too) need to be aware of this well established point. Yes, PSA levels will be lower when a man is taking finasteride. If he and his doctor want to use old reference triggers for biopsy, they can simply double his PSA result and track trends that way. If a doctor is not aware of that, hopefully he won't be dealing with us. We deserve better! Essentially, Dr. Walsh is concerned that some bad medicine is being practiced, but that is not news. Hopefully, doctors who screen us for prostate cancer are now or will soon become aware of how to look at PSA results for a man on a 5-ARI drug. The solution is not to avoid 5-ARI drugs for prevention; rather the solution is to educate the doctors (and again, hopefully educate us patients so we can act as quality control for our own health monitoring).

In support of his second point, Dr. Walsh emphasizes a most interesting result: "... when PSA levels increased in men who were on finasteride, their risk of having cancer was three-fold [meaning three times] higher than in men without a rise and six-fold higher for being diagnosed with high-grade disease." But this really does not support Dr. Walsh's overall argument against using finasteride for prevention; instead it amplifies the benefits of finasteride! Consider that, for those men who did need a biopsy despite taking finasteride, 10% fewer had a positive biopsy, according to what Dr. Walsh told us earlier in his letter. *****Yet, for those on finasteride, the payoff for going through the trouble, expense and anxiety of having a biopsy was three times higher for men on finasteride, and, for those who happened to have high grade disease, the biopsy was six times more likely to find that high grade disease than were biopsies for men who were not on finasteride!***** [On 10/18 late, I noticed that these words between the asterisks need to be rephrased; the comparison was within the finasteride group, not to those who had not had finasteride. I'll work on that.] I had not been aware of the three-fold and six-fold figures, but properly viewed, they are stunning: far more bang for the buck from biopsies for men on finasteride! Dr. Ian Thompson and other finasteride experts have been saying in a slew of papers that finasteride makes PSA analysis and DRE interpretation more effective, but I had no idea on the dramatic effect on biopsies as well. Wow! Thanks medved for calling Dr. Walsh's views to the board's attention with this priceless piece of information!

Dr. Walsh's third point is short: "Third, the authors [of a pro-finasteride paper he is responding to] are advocating the off-label use of a drug that is not approved by the US Food and Drug Administration as safe or effective in preventing prostate cancer." That's true. However, it is also trivial. Regarding safety, the massive PCPT trial and long experience with finasteride for BPH have established that finasteride is a remarkably mild and safe drug, though with some concerns, as is the case with virtually every drug. Of course, the FDA has approved both finasteride and Avodart as safe and effective for BPH, following expensive, large trials by the companies that developed and hoped to market the drg. Regarding effectiveness, the PCPT established that, and the powerful trial result evidence is further bolstered by the recently informally reported success in prevention by the sister drug, Avodart, also achieving about 25% prevention. The oncologist community (in contrast to the surgical community) is keenly aware that, due to the great expense and effort in winning FDA approval for drugs, many highly useful drugs against specific diseases are not FDA approved for those diseases. (What do you think the chances are that some company will spend major bucks to prove the benefit of a drug that is now generic? Probably not likely.) However, they are frequently used under what are termed "off-label" procedures for those diseases, and doctors and the FDA are quite comfortable with that. I'm not an MD, but as I understand it, a drug that is approved by the FDA for one disease can be used by a physician to treat another disease provided he explains the risks and benefits to the patient.

I can also comment on what I believe is an ingrained bias at Johns Hopkins against finasteride for prostate cancer, but that's another story involving my own personal experience. I had hoped the Johns Hopkins community had come up to speed on 5-ARIs, but now I'm thinking that that has not yet happened. Also, I'm no longer surprised when I see true experts making faulty calls when they venture beyond the areas of their expertise. These are very smart folks at Johns Hopkins - wonderfully dedicated and talented, and when they take off the blinders that we all wear from time to time - often blinders created by obsolete or misinterpreted experience, I'm confident they will climb on board the 5-ARI bandwagon.


Does anyone know of a well-respected prostate cancer expert who is recommending the use of 5 alpha-reductase inhibitors for chemoprevention purposes in high risk individuals who do not otherwise need these drugs (in other words, who do not have BPH)? ...
Yes, there are quite a few. I'll start with one of the original skeptics, whose influential negative words about finasteride had quite an impact: the world renowned prostate cancer surgeon at Memorial Sloan Kettering - Dr. Peter Scardino; he now favors use of finasteride for prevention. Dr. Ian Thompson, chair of the Department of Urology at the University of Texas Health Science Center at San Antonio, a leader in the finasteride research, is another highly regarded heavy hitter who advocates use of finasteride. Dr. Eric Klein, a renowned urology leader at the famous Cleveland Clinic, is one more heavy hitter who campaigns for and educates physicians and researchers about finasteride use for chemoprevention. A number of eading experts in hormonal blockade therapy have long been convinced that 5-ARI drugs would prove out. They include Dr. Robert Leibowitz, Dr. Stephen Strum, Dr. Charles Myers, Dr. Mark Scholz, Dr. Richard Lam, Dr. Stephen Tucker, and others. At a conference a couple of years ago, I heard Dr. Fernand Labrie from Quebec, who is generally credited as the "Father of Combined Hormonal Blockade," said he was changing his view and now believed that finasteride added extra impact to hormonal blockade; I suspect he now also advocates it for prevention. There are others, but these men are more prominent and most would qualify as "heavy hitters."

If you have questions and follow-up concerns, please raise them.

I hope this helps, and thanks again for bringing up the issue.

Jim

Last edited by IADT3since2000; 10-18-2009 at 05:48 PM. Reason: Added brief phrase right after posting. Late on 10/18, realized words between the asterisks need to be rephrased.

 
Old 10-17-2009, 05:04 PM   #3
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Re: chemoprevention of prostate cancer

Jim,
As someone with a rising PSA and two (negative so far) biopsies, I'm very interested in the studies on finasteride and dutasteride and have been considering taking one or the other as a preventative. However, I'm a little confused by the following quote.

Quote
In support of his second point, Dr. Walsh emphasizes a most interesting result: "... when PSA levels increased in men who were on finasteride, their risk of having cancer was three-fold [meaning three times] higher than in men without a rise and six-fold higher for being diagnosed with high-grade disease."

Taking this literally, Walsh seems to say that people on finasteride were at higher risk for cancer. However, I think what you are saying is that the "risk" of having an increasing PSA above the baseline (lower for finasteride takers) is much less for those taking finasteride. Thus, even though the risk of those with a rising PSA to have cancer is 3 times higher, there are much fewer of those taking finasteride that have a rising PSA, so the overall risk of having cancer ends up lower for those taking finasteride. Did I parse this correctly?

Quote
Yet, for those on finasteride, the payoff for going through the trouble, expense and anxiety of having a biopsy was three times higher for men on finasteride, and, for those who happened to have high grade disease, the biopsy was six times more likely to find that high grade disease than were biopsies for men who were not on finasteride!

I'm interpreting this to mean that an increased "payoff" means an increased sensitivity of the biopsy, i.e. fewer false negatives. My recollection from some of original papers interpreting finasteride work was that the increased sensitivity was due to smaller prostate volume, so the biopsy sampled a larger fraction of the prostate. Is this approximately correct?

I don't mean this as criticism; in fact I (think I) agree with your conclusions. I am far less expert and am just trying to understand the arguments. I very much appreciate the thoroughness of your comments.

By the way, I discussed taking finasteride as a preventative with my urologist last year, and he was negative on the idea. That was after the statistical papers that "debunked" the conclusion that finasteride was causing high grade cancer, but before the recommendations came out (from NCI I think?) that doctors should discuss this option with patients. He said that for BPH (of which I probably have a little) he would prefer patients to take (as I recall) an alpha blocker. I have also read that statins provide some PC prevention. I wonder if you have an opinion of statins versus finasteride/dutasteride as preventive agents.

Larry

 
Old 10-17-2009, 05:22 PM   #4
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Re: chemoprevention of prostate cancer

Jim -

You are right about Walsh's letter generating a response -- the study authors (or at least some of them) promptly responded to the letter. Again, I would post a link to the response here, but not sure I am permitted to do so. The substance of the response will not surprise you, though, given your observations.

I thought the "off label use" argument was particularly weak -- a sort of "throw away" argument at the end of the letter. As you point out, off label use of FDA approved drugs is nothing new. For example, ketoconazole is used "off label" for advanced prostate cancer -- as far as I know without much controversy.

The issue about the 15% who did not get biopsies seems more complex to me. If the did not get biopsies because they did not need biopsies, then that's great. But if they did not get biopsies because their psa was lowered to a level where they did not think it was necessary, then that raises some questions. (Of course, as you point out, the answer to "people will be lulled into complacency" may be "they should not be" -- rather than refusing to use a drug that could prevent cancer).

One thing I am thinking about, though, is whether there is real certainty about the extent to which finasteride (or dutasteride) reduces psa levels -- particularly over many years of taking it. (If I start this, I could potentially be on it for a very long time). If there is uncertainty, it could make psa monitoring more complicated, even if I am not lulled into complacency -- particularly if the extent of the reduction increases over time, at a less-than-entirely-predictable rate.

By the way, for the web article by Dr. Catalona on this topic (which again I am not linking here for fear of violating a board policy) you can search on google for "Catalona finasteride prevention" and you will see it.

Regarding Dr. Scardino, I did read of his change of position about this, which I found pretty pursuasive -- though I also saw he said that he is not personally taking it. It would be very interesting to know whether the other doctors who avocate finasteride for preventative purposes personally take it. (Sort of like asking the surgeon "who would you choose to operate on your son?").

Regards,

Medved

 
Old 10-17-2009, 05:28 PM   #5
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Re: chemoprevention of prostate cancer

A JHU urologist with whom I spoke said in his view there is not sufficient evidence to support prescribing statins for the prevention of prostate cancer. (Of course, other docs -- there or elsewhere -- might disagree with that).

He also said -- and this is a separate point from the one above -- that the extent of psa reduction caused by statins is not sufficient so that they feel they need to "adjust" for it in monitoring psa levels (unlike finasteride, where obviously it needs to be taken into account).

 
Old 10-17-2009, 06:59 PM   #6
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Re: chemoprevention of prostate cancer

Worth reading a June 15, 2008 article from the New York Times (available on line) entitled "New Take on a Prostate Drug, and a New Debate."

 
Old 10-18-2009, 02:06 PM   #7
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Re: chemoprevention of prostate cancer

Cost of Finasteride Overestimated by Dr. Walsh

Hi again medved and all interested in chemoprevention by finasteride (and Avodart). I had another comment on Dr. Walsh's letter to the journal, which you mentioned as follows and which I addressed in the 2nd post:

Quote:
Originally Posted by medved View Post
I have been interested recently in the subject of chemoprevention of prostate cancer using finasteride or dutasteride. ... However, I recently read a letter by Dr. Walsh at JHU recommending against using these drugs for chemoprevention...
Dr. Walsh wrote that men could save $700 to $1,000 a year as the cost of finasteride not covered by insurance. However, those figures look really high to me. In mid-July my 90 day, 180 pill finasteride prescription cost my insurer (all cost, including any copay from me) just $140.65, or $.7813 - less than $1 - per pill. Multiplied by 365, for 1 pill per day for a year, the projected cost would be $285, far lower than Dr. Walsh's estimated range. My very large, very well known insurance company charges me nothing for the first four refills of generics a year, and after that just $10 for each three month supply.

Moreover, it is almost a certainty that that cost would drop even further if a large number of men used finasteride for prevention, allowing lower costs for large production quantities.

I hope to address some of the other concerns on this thread soon.

Jim

 
Old 10-18-2009, 05:26 PM   #8
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Re: chemoprevention of prostate cancer

The value of statin drugs for prostate cancer patients and men at elevated risk for prostate cancer

Hi Medved,

I'm responding to your post below about the JHU urologist's opinion of statin drugs for prostate cancer:


Quote:
Originally Posted by medved View Post
A JHU urologist with whom I spoke said in his view there is not sufficient evidence to support prescribing statins for the prevention of prostate cancer. (Of course, other docs -- there or elsewhere -- might disagree with that).

I believe a strong or complete consensus of leading experts who are knowledgeable about drugs for prostate cancer - probably not including very many urologists - would agree as the evidence that statins reduce the incidence of prostate cancer is not yet strong and well may not become strong. Most research do not indicate that statins prevent prostate cancer. But that is not at all the point.

The value of statins for prostate cancer, supported by accumulating research is a rather strong reduction in the risk of dying from prostate cancer, and of more advanced disease! (Did the Johns Hopkins urologist bring that up?) Moreover, research indicates that the degree of protection from lethal prostate cancer is greatest when statins have been taken for three years or more. (I've tried to find the references in my notes and in PubMed without specific success; there are many medical research papers suggesting decreases in advanced disease of around 25% to 40% - quite a benefit!) As statins are a benign drug for the vast majority of us (my layman's opinion based on what I've read and heard - no enrolled medical education), and as many of us could use some help in controlling our cholesterol, it seems that many men at risk for prostate cancer should consider taking statins before they are diagnosed.

I'm not thinking just about men with generally increased risk for prostate cancer due to race or family history, but more specifically about men who are concerned because of PSA results, free-PSA results, PCA3Plus results, DRE results, and "high-grade PIN" findings at biopsies that are still negative for cancer. Taking a statin for a fairly hypothetical risk of prostate cancer in the general population would be at least somewhat controversial, as the Johns Hopkins doctor suggests, but, from where I stand as a survivor with a challenging case, the case for statins is much more persuasive for a man with screening evidence that prompts concern over prostate cancer.

I am dealing with a challenging case of prostate cancer, and one of my few regrets in treatment decisions is that I did not start taking a statin earlier; I was reluctant to add another drug to my regimen and run the risk of some muscular side effects, which I did not realize were very low. (In his Prostate Forum newsletter, Vol. 8, #11, January 2005, Dr. Charles "Snuffy" Myers, contrasting statins with riskier drugs like Vioxx and Bextra, and even Celebrex and Aleve, wrote "... On the other hand, some drugs, such as statins (Lipitor, Zocor and Pravacol) are much safer than previously thought: we now know that serious muscle problems only occur in only 1 out of 20,000 patients." I have now been on simvastatin for about 2 1/2 years, so I soon will be approaching the maximum protection zone. I take it with Co-Q-10 as that is known to prevent one usually minor side effect.

If you want to learn about what is currently known and thought about statins and advanced/lethal prostate cancer (or reducing incidence), try our friend PubMed at www.pubmed.gov. I just did that to make sure I had the facts straight, and I got 116 tonight using the search string (without the quotation marks) " prostate cancer AND statin ". One prominent researcher looking into this is Elizabeth (EA) Platz, ScD and MPH, from the renowned group of prostate cancer researchers at Johns Hopkins. If you find the reference to best impact from three years and greater use, I would appreciate it if you posted that.

Jim


...

Last edited by IADT3since2000; 10-18-2009 at 05:39 PM. Reason: Added words to end of subtitle: "and men at elevated risk for prostate cancer"

 
Old 10-18-2009, 06:02 PM   #9
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Re: chemoprevention of prostate cancer

Jim
I had a couple of questions (post #3 of this thread) about your post #2. I suspect it was missed due to the jump from page 2 to 1.

Larry

 
Old 10-18-2009, 06:44 PM   #10
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Re: chemoprevention of prostate cancer

Quote:
Originally Posted by medved View Post
One thing I am thinking about, though, is whether there is real certainty about the extent to which finasteride (or dutasteride) reduces psa levels -- particularly over many years of taking it. (If I start this, I could potentially be on it for a very long time). If there is uncertainty, it could make psa monitoring more complicated, even if I am not lulled into complacency -- particularly if the extent of the reduction increases over time, at a less-than-entirely-predictable rate.
I did see one data point on this in the 2008 AUA Clinical Practice Guidelines. This is a quote-Underline added for emphasis.
5-ARIs effect on PSA. The decrease in PSA levels by 5-ARIs must be taken into account when judging the significance of a PSA level. In the PCPT, finasteride lowered the PSA by 50% after 12 months of therapy, and therefore a multiplier of 2 was used as a criterion for biopsy. The effects of 5-ARIs on PSA before 12 months are variable. In the PCPT, the decline at 3 years was greater than 50% which was adjusted by changing the 2 multiplier in the finasteride arm to 2.3.

 
Old 10-19-2009, 08:50 AM   #11
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Re: chemoprevention of prostate cancer

Quote:
Originally Posted by holler1 View Post
I did see one data point on this in the 2008 AUA Clinical Practice Guidelines. This is a quote-Underline added for emphasis.
5-ARIs effect on PSA. The decrease in PSA levels by 5-ARIs must be taken into account when judging the significance of a PSA level. In the PCPT, finasteride lowered the PSA by 50% after 12 months of therapy, and therefore a multiplier of 2 was used as a criterion for biopsy. The effects of 5-ARIs on PSA before 12 months are variable. In the PCPT, the decline at 3 years was greater than 50% which was adjusted by changing the 2 multiplier in the finasteride arm to 2.3.

Yes, I have seen that too. But my question is does finasteride really reduce every patient's psa after 12 months by 50% or is that just, as I suspect, an average? And at three years, they say "more than 50%" and therefore multiply by 2.3x. Again, I have to assume that is just an average and that for some people the reduction will be more, or less. And what about at 7 years, or 15 years, or 23 years? Nobody seems to know. It therefore seems to me (a totally uneducated layperson) that taking finasteride for prevention purposes -- while probably having some material benefits -- also carries with it some risk of "masking" prostate cancer. That is one thing I am thinking about it making my own decision on this.

By the way, there may be similar risk with statins, which apparently reduce psa levels, though not nearly as much as finasteride. The Harvard Health Letter (2/1/2009), citing the JNCI November 5, 2008, reported average 4% psa reduction with statin use (and 9% with aspirin). Of course, again that is just an average. The article stated in part: "The reductions weren't large, but the researchers were concerned that they could hide important changes in PSA that migh interfere with the detection of prostate cancer. Another tantalizing possibility is that aspirin and statins fight prostate cancer. It would take some very large, very long trials tod etermine if that is the reason for the decrease."

There have been some studies, I believe, suggesting that statin use may reduce the risk of p ca, or at least lethal p ca. But they have, I believe, been restrospective, and there does not -- as best I can tell -- exist any consensus that the evidence is strong enough for a clinical recommendation.

Of course, statins might be useful anyway, for other purposes. And if that is the case, then someone could reasonably conclude "I will take the statins anyway, for other purposes, knowing that maybe there is a prostate cancer related benefit too." But what I am wondering is whether there is more prostate related benefit (risk reduction) or harm (masking).

 
Old 10-19-2009, 07:47 PM   #12
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Re: chemoprevention of prostate cancer

Hi medved and holler1,

I can add to the discussion with some thoughts and facts about the following excerpts from medved's post #11, in green. I'm also trying to get to the earlier posts with still unaddressed good questions. You guys are really thinking this through and asking some excellent questions! Jim


Quote:
Originally Posted by medved View Post
Yes, I have seen that too. But my question is does finasteride really reduce every patient's psa after 12 months by 50% or is that just, as I suspect, an average?

It is certainly "just" an average, but it's considered a quite reliable rule of thumb. I've seen some studies where the long-term reduction of PSA due to finasteride was more like 40%. Probably a heavy majority of men with healthy prostates would experience a drop of 40% to 50% or more, though I have not reviewed the studies to confirm that.

Some of the leading doctors are now using this typical decrease as an additional clue to whether a patient has prostate cancer, a technique known as "finasteride challenge". Dr. Eric Klein of the Cleveland Clinic explained it this way. If his patient's PSA dropped by about 50% or more in six months, then Dr. Klein was reasonably confident that he did not have prostate cancer and could be monitored routinely. However, if the decline in PSA was much less than 50% at about six months, Dr. Klein accelerated PSA and other testing to smoke out any prostate cancer.


And at three years, they say "more than 50%" and therefore multiply by 2.3x. Again, I have to assume that is just an average and that for some people the reduction will be more, or less. And what about at 7 years, or 15 years, or 23 years? Nobody seems to know.

I suspect the Prostate Cancer Prevention Trial participants are being followed up for longer term results, at least some of them. One of us could check that. Based on the way the drug works, the reduction should continue at about the same level more or less indefinitely, as I understand it, unless disturbed by cancer or infection/inflammation.

About that 15 years or 23 years forecast - It's very likely that some even better approach will emerge in either timeframe. It will be quite surprising if the 5-ARI drugs are the best we have for prostate cancer prevention fifteen years from now. There has been amazing progress in prostate cancer just in the nearly ten years since my own diagnosis, and it's likely that pace will accelerate. I can give some examples if you would like to see them.


It therefore seems to me (a totally uneducated layperson) that taking finasteride for prevention purposes -- while probably having some material benefits -- also carries with it some risk of "masking" prostate cancer. That is one thing I am thinking about it making my own decision on this.

"Masking" is an old, now obsolete concern, though it's a certainty there are doctors out there who have not kept up and still subscribe to the masking theory. As I understand it, trial results and expert analysis have now virtually proven that finasteride does not allow a stealthy attack by cancer that grows under the radar, cloaked by finasteride. On the contrary, to use an engineering analogy, finasteride reduces the noise in the PSA signal so that it is a much more sensitive indicator of prostate cancer. It does the same for the DRE.

In essence, finasteride reduces BPH, thereby reducing "clutter" from PSA resulting from BPH. It is hypothesized but has not been proven by finasteride experts that finasteride is fairly good at curing small amounts of the less aggressive forms of prostate cancer, but the experts also believe it is not effective against higher grade prostate cancer, at least not alone, and that widespread consensus is firmly supported by research.


By the way, there may be similar risk with statins, which apparently reduce psa levels, though not nearly as much as finasteride. The Harvard Health Letter (2/1/2009), citing the JNCI November 5, 2008, reported average 4% psa reduction with statin use (and 9% with aspirin). Of course, again that is just an average. The article stated in part: "The reductions weren't large, but the researchers were concerned that they could hide important changes in PSA that migh interfere with the detection of prostate cancer.

My take is that the researchers and physicians feel that the rather small amount of the PSA reduction is too little to worry about as a masking factor. The reduction is far less than the reductions caused by finasteride.

Another tantalizing possibility is that aspirin and statins fight prostate cancer.

I'm confident evidence will continue to build that statins fight prostate cancer, and that may well be true for NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) like aspirin as well.

It would take some very large, very long trials tod etermine if that is the reason for the decrease."

That likely true if we want absolute proof. Personally, I don't need that high a level of evidence for these quite safe drugs (at low dosages, with patient circumstances considered).

There have been some studies, I believe, suggesting that statin use may reduce the risk of p ca, or at least lethal p ca. But they have, I believe, been restrospective, and there does not -- as best I can tell -- exist any consensus that the evidence is strong enough for a clinical recommendation.

I really doubt that there is such a consensus among surgeons, whose main expertise and focus is not drugs, but I suspect there is such a consensus among medical oncologists who treat many prostate cancer patients. PSA is made from cholesterol, by the way. (I'm not sure whether that point has been made yet on this thread.) Dr. Charles Myers, an expert medical oncologist specializing in prostate cancer (and a former drug researcher at NIH, as well as being a patient with a challenging case of prostate cancer himself), is a strong advocate of the use of statins for men who have or are at risk for having prostate cancer, provided their personal health circumstances are appropriate. (He judges statins at lower doses to be mild drugs for the vast majority of us, as I understand it. He does recommend taking a small amount of Co-Q-10 daily when we are on a statin drug.)

Of course, statins might be useful anyway, for other purposes. And if that is the case, then someone could reasonably conclude "I will take the statins anyway, for other purposes, knowing that maybe there is a prostate cancer related benefit too."

That's right on the money - a dual (at least) benefit!

But what I am wondering is whether there is more prostate related benefit (risk reduction) or harm (masking).

I'm convinced there is very substantial benefit, low risk, and no masking in the hands of a knowledgeable doctor.

Jim

Last edited by IADT3since2000; 10-19-2009 at 07:56 PM. Reason: Added comment about 15 and 23 year forecasts.

 
Old 10-20-2009, 05:37 PM   #13
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Re: chemoprevention of prostate cancer

Quote:
Originally Posted by IADT3since2000 View Post
Some of the leading doctors are now using this typical decrease as an additional clue to whether a patient has prostate cancer, a technique known as "finasteride challenge". Dr. Eric Klein of the Cleveland Clinic explained it this way. If his patient's PSA dropped by about 50% or more in six months, then Dr. Klein was reasonably confident that he did not have prostate cancer and could be monitored routinely. However, if the decline in PSA was much less than 50% at about six months, Dr. Klein accelerated PSA and other testing to smoke out any prostate cancer.
This is an interesting approach that I had not heard about. If I do turn out to have PC, Cleveland Clinic is one of my top choices for treatment because of location and excellence. I've heard a lot about Klein.

One other item I ran across just now in doing a PubMed search is an article on risk reduction by finasteride and alpha blockers in the Finnish Prostate Cancer Screening Trial, by researchers at the University of Tampere, Finland. It isn't completely clear to me how much it is advisable to quote from a public abstract. However, I'm appending below a short quote on their results. They found no significant change in overall PC incidence, but a significant reduction in Gleason 2-6 cancers. For alpha blockers, again there was no significant change overall, but a significant reduction in high grade cancers. The abstract doesn't say whether/how the screening approach might have affected the results, i.e. did they use a fixed PSA cutoff to trigger biopsy that might bias the results? On the surface, it might imply that taking both an alpha blocker and finasteride would be preventative, but that finasteride alone might affect only less significant cancers.

Using a comprehensive prescription database on medication reimbursements during 1995-2004 of men using finasteride or alpha-blockers for benign prostatic hyperplasia, we evaluated prostate cancer incidence among 23 320 men screened during 1996-2004. RESULTS: Compared to medication non-users, overall prostate cancer incidence was not significantly affected in finasteride users (hazard ratio 0.87; 95% CI 0.63-1.19). Incidence of Gleason 2-6 tumours, however, was decreased among finasteride users (HR 0.59; 95% CI 0.38-0.91), whereas incidence of Gleason 7-10 tumours was unchanged (HR 1.33; 95% CI 0.77-2.30). The protective effect concerned mainly screen-detected tumours. Overall prostate cancer risk was not significantly reduced among alpha-blocker users relative to non-users, but decreased incidence of high-grade tumours was observed (0.55; 95% CI 0.31-0.96). CONCLUSIONS: The detection of low-grade, early-stage tumours is decreased among men who use finasteride for symptomatic BPH. The protective effect of finasteride can also be expected in men with benign prostatic hyperplasia.

I keep hoping the dutasteride trials will come out soon and show good results for both low grade and high grade PC. The "general expectation" seems to be that dutasteride might be better than finasteride, but it would be nice to see more confirmation than the preliminary presentation results.

Thanks again to IADT3since2000 and medved for taking seriously the comments and questions by an "unofficial member" of the forum like myself. I realize that my concerns are much less urgent than many of the other posters who are in the throes of treatment selection.

 
Old 11-04-2009, 06:12 PM   #14
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Re: chemoprevention of prostate cancer

On the subject of prevention, there is a news report out today that reports on the preventive effect of low cholesterol. Here is a short quote.
One study found that men whose cholesterol was in a healthy range — below 200 — had less than half the risk of developing high-grade prostate tumors compared to men with high cholesterol. A second study found that men with lots of HDL, or "good cholesterol," were a little less likely to develop any form of prostate cancer than men with very low HDL.

I thought I would mention that both articles mentioned are currently available in full text on the web site of the journal (I won't mention the journal's name but it is mentioned in the news article). The first article especially has a lot of details on the study. It was based on the placebo arm of the well-known PCPT study and the statistics look pretty solid to me (as a retired physicist). The authors were unable to discern whether statins had any role in cholesterol levels in the study.

 
Old 11-14-2009, 04:29 PM   #15
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Re: chemoprevention of prostate cancer

Hi holler1,

I'm responding to your posts #13 and #14 (excerpt below from #13) with some comments in green.


Quote:
Originally Posted by holler1 View Post
...One other item I ran across just now in doing a PubMed search is an article on risk reduction by finasteride and alpha blockers in the Finnish Prostate Cancer Screening Trial, by researchers at the University of Tampere, Finland. ... They found no significant change in overall PC incidence, but a significant reduction in Gleason 2-6 cancers. For alpha blockers, again there was no significant change overall, but a significant reduction in high grade cancers.

Thanks for pointing out the Finnish study. It's nice to see these results that line up with the PCPT and dutasteride results (see mention below).

The abstract doesn't say whether/how the screening approach might have affected the results, i.e. did they use a fixed PSA cutoff to trigger biopsy that might bias the results?

There is a Government website for locating medical libraries that are accessible by the public. Unfortunately, I cannot put my finger on the address at the moment. Since you are interested in research, you might want to try to find a local resource. My local hospital has a very helpful library. Sometimes I drive over, but often I just send an email and get a scanned copy of a paper in return. It's a terrific service! You might be able to find the same kind of arrangement.

On the surface, it might imply that taking both an alpha blocker and finasteride would be preventative, but that finasteride alone might affect only less significant cancers.

My impression is that the statement about finasteride is the consensus of the experts about finasteride, but it may also have some other subtle effects. It is known for reducing blood supply to tumors, and that would affect all tumors I think.

...

I keep hoping the dutasteride trials will come out soon and show good results for both low grade and high grade PC. The "general expectation" seems to be that dutasteride might be better than finasteride, but it would be nice to see more confirmation than the preliminary presentation results.

Yes! If you spot the published results, please let the board know.

Thanks again to IADT3since2000 and medved for taking seriously the comments and questions by an "unofficial member" of the forum like myself. I realize that my concerns are much less urgent than many of the other posters who are in the throes of treatment selection.

Maybe less urgent, but not less important! To me prevention of prostate cancer is a high priority!

Thanks for your post about the just published analysis of statins in the placebo arm of the PCPT trial. I was not aware of that paper and am most interested in the topic. By the way, I've been really pleased with the way I've responded to simvastatin in conjunction with a nutrition/diet/supplement program to counter prostate cancer. My results on June 6, 2009 were: total cholesterol 198, HDL 87 (! ), LDL 101, and trigs just 49. My doctor leafed through my file to check my cholesterol results, and when he saw that HDL he said "Wow" and his eyebrows raised in awe. I have a friend who also diligently pursues a similar program, and his HDL was even higher at 95! Those side-effect countermeasures can really do the job!

Take care,

Jim

 
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