Nobody wants to find himself in a place where he wonders how he got there and can't see a way out either
Plain and simple. No matter what this study reported, I do not and cannot recommend taking Avodart to prevent prostate cancer.
I have a difficult time even recommending it to relieve symptoms of severe enlarged prostate - where I know it's effective - because of my concerns that it masks prostate cancer.
I have the same feelings about Avodart that I have about finasteride (Proscar®).
Although media coverage of the Avodart study suggested that Avodart is different from finasteride, I see the potential negatives as similar.
My Recommendations
Until further information is available, I recommend only the FDA-approved use of either drug in men with severe symptoms from benign prostatic enlargement who have not responded to alpha-blocker therapy (such as Flomax®) and want to delay surgical intervention for relief of urinary obstruction. Neither Proscar nor Avordart is approved by the FDA for prostate cancer prevention.
My warning is: Avodart and Proscar might mask high-grade prostate cancer.
I recommend a prostate biopsy to rule out cancer before starting either drug, and I recommend a repeat biopsy if the PSA rises while a patient is taking Proscar or Avodart after I have ruled out other possible causes for the PSA increase.
Masking Cancer
In the summer/fall 2008 Quest, I wrote extensively about my concerns over suggestions that men should consider taking Proscar every day to prevent prostate cancer. That article, The Finasteride Controversy: Questions About Safety Remain, is available on my website: www.drcatalona.com
The explanations for how and why both drugs can mask prostate cancer are similar, and the detailed explanation in my article on Proscar holds true for Avodart as well.
These drugs shrink less aggressive tumors more than they do the most serious kind. If you give a man any hormone therapy that reduces the amount or effects of natural male hormones, and that's basically what these drugs do, it will temporarily lower PSA scores. But I don't think they are preventing prostate cancer, just delaying its eventual detection.
I'm even more concerned after hearing about men taking Avodart as a preventative because prostate cancer runs in their family. They are the last people who should be taking it for that reason.
Interpreting the Facts
In the Avodart study, the researcher said there was no significant increase in the percentage of "high-grade" tumors detected in the Avodart arm of the study.
In fact, participants in the Avodart arm of the study had 29 Gleason grade 8-10 tumors and those in the placebo arm had 19. Because of the number of participants in the study, these differences were described as statistically insignificant.
Viewed another way, though, the rate of Gleason 8-10 prostate cancer was 50% higher in the Avodart arm, and more than 76% of the Gleason 8-10 tumors were detected in men taking Avodart. Statistically, this disparity would be expected to occur by chance alone in only about 1 of 10 instances.
With further follow-up - but, to my knowledge, no follow-up is planned - more high-grade tumors should emerge, and, eventually, Avodart may no longer control some of the lower-grade elements.
In a clinical trial with longer (15 to 20 years), it is possible and, in my opinion, probable that "masking" high-grade prostate cancer with Proscar or Avodart until it is too late for cure would outweigh any benefits from delaying or preventing the detection of lower-grade cancers.
Time Limits Affect Results
If a prostate cancer chemoprevention study has a limited time span of 4 to 7 years (such as the Proscar and Avodart studies) a delay in cancer detection would produce the appearance of a decrease in cancer incidence. However, with longer follow-up, this apparent benefit would substantially diminish or disappear.
This situation was, in fact, the case in the prostate Cancer prevention Trial (the Proscar Study) among patients who had a biopsy "for cause." In this trial that lasted for almost 7 years, by the last year, the number of cancers in the placebo arm and in the finasteride arm was nearly equal, but 52% of the cancers in the finasteride arm were high-grade as compared with only 31% in the placebo arm.
I would predict that the Avodart study, if continued, would show the same results. Avodart is unlikely to reduce prostate cancer deaths and may even increase them by masking high-grade disease until it is too advanced to cure.
No Easy Fixes
It is more than unfortunate that still we are still unable to tell men diagnosed with prostate cancer what their future could be with or without treatment. Now, with any disease where there is an attempt at early detection, some patients who would not have suffered or died of the disease are treated. Thus, with all attempts at early detection or prevention, there will be "overdiagnosis" and "overtreatment." But without early detection, many more men, with dire consequences, are "underdiagnosed" and treated too late.
Prostate cancer is a disease that can be cured if caught early. The PSA test, with all its helpful and recent variations, is the best one for early detection of prostate cancer. It is not perfect, but it is more reliable than almost every other cancer-detecting test.
Since the PSA testing era, there has been a 75% decrease in advanced prostate cancer at diagnosis and in the U.S. the prostate cancer death rate has now decreased by more than 40% during the PSA era (1991-2006).
Prostate cancer is the most common non-skin cancer in American men. One of every 6 men will be diagnosed with prostate cancer. An estimated 192,280 new cases and 27,360 deaths from it are estimated to occur in 2009. It is a serious health concern for men and a complicated disease.
My hope is that research will find answers for the treatment, cure and prevention of prostate cancer without surgery. I, and my research collaborators, spend a great deal of time and energy on such a search. We learn more that will ultimately improve treatment all the time. But we still have a way to go.
At present, we need to find the cancer early and get rid of it before it spreads.
We cannot look to easy fixes.
In my opinion, Avodart is unlikely to reduce suffering and death from prostate cancer, but it has the long-term potential for setting back prostate cancer treatment and possibly allowing more advanced prostate cancer cases to progress beyond the possibility of cure.
reprinted from Quest Summer/Fall 2008 but using dutasteride (Avodart) as the drug example.
A man who has benign prostate enlargement as well as a yet- undetected prostate cancer - that is largely composed of low-grade cancer cells but also contains a small proportion of high-grade cancer cells - is started on Avodart therapy for cancer prevention.
With the initiation of Avodart therapy, the normal prostate cells regress, decreasing the PSA contribution from normal prostate tissue.
The benign enlargement tissue also regresses, additionally decreasing the PSA from the benign hyperplasia component. And the low-grade prostate cancer regresses, further decreasing the PSA level. As a result, the PSA levels decrease.
However, the high-grade prostate cancer cells might continue to grow unchecked and, because high-grade prostate cancer produces less PSA per cell, PSA levels might not increase until regression of benign and low-grade cancer is near complete.
Therefore, by the time the PSA begins to rise or reach the threshold for biopsy, most of the remaining prostate cancer might be composed of aggressive, high-grade disease that has a less favorable prognosis.
In contrast, if this man were not taking Avodart, his PSA would not decrease but rather would continue to rise and trigger concern because of the PSA velocity or reach the PSA biopsy threshold sooner.
Moreover, men with a rising PSA would be more likely to comply with the recommendation for a biopsy, and the biopsies would be found to contain relatively more low-grade and less high-grade prostate cancer, with a far more favorable prognosis.
Thus, I believe Proscar or Avodart can lull a man and his doctor into a false sense of security.