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Cancer: Prostate Message Board

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[COLOR="DarkGreen"]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:[/COLOR]

[QUOTE=medved;4101582]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.

[COLOR="DarkGreen"]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? [I][U]It isn't! That fifteen percent is part of the evidence for prevention![/U][/I] 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% [I][U]deserve[/U][/I] to be added, and the combined reduction [I][U]is[/U][/I] 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) [I][U]need to be aware[/U][/I] 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. [I][U]If a doctor is not aware of that, hopefully he won't be dealing with us. We deserve better![/U][/I] :( Essentially, Dr. Walsh is concerned that some bad medicine is being practiced, but that is not news. :mad: 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! :D Consider that, for those men who did need a biopsy despite taking finasteride, [U][I]10% fewer[/I][/U] had a positive biopsy, according to what Dr. Walsh told us earlier in his letter. *****Yet, for those on finasteride, the [I][U]payoff[/U][/I] for going through the trouble, expense and anxiety of having a biopsy [I][U]was three times higher[/U][/I] for men on finasteride, and, for those who happened to have high grade disease, the biopsy was [I][U]six times[/U][/I] 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: [I][U]far more bang for the buck[/U][/I] 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! :D :cool: 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.[/COLOR]

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)? ...[/QUOTE]

[COLOR="darkgreen"]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 :wave:[/COLOR]

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