We've all heard the phrase, "When you come to a fork in the road, take it." Well, that saying may hold particular relevance while reviewing a new research report published today in the New England Journal of Medicine.
The report is an important one. It is an 18 year follow-up of a study designed to show whether the use of the drug finasteride could reduce the incidence and deaths from prostate cancer. The study was called the Prostate Cancer Prevention Trial and when it was initially reported in 2003 it showed that the drug could reduce the incidence of prostate cancer by almost 25%. However, there was a catch: there was actually an increase of almost 27% in the number of high grade-or more serious-prostate cancers in the group treated with finasteride compared to those men who did not get the drug. The men in this trial were followed very closely. Since this trial was done in an era when PSA testing to find prostate cancer "early" was part of routine care, these men were screened regularly with the PSA test.
The originally reported results of the trial meant two things to the researchers: first, finasteride was successful in reducing the frequency of prostate cancer, but most of that decrease was in the lower grade, less harmful forms of the disease, and second, it raised the question of whether the drug actually promoted more serious forms of prostate cancer. Some experts argued that in fact there weren't more numerous high grade tumors, only that finasteride made it easier to find them thanks to the fact that it shrinks the prostate.
The debate on the relative merits of using finasteride has continued since. Suffice to say, the use of the drug didn't get much traction. In 2011, the Food and Drug Administration added information to the drug label that finasteride and similar drugs could increase the frequency of more lethal forms of prostate cancer and that the drugs were not approved for prostate cancer prevention.
Meanwhile, organizations such as the American Cancer Society have suggested that men should make an informed decision as to whether or not they really want to be screened for prostate cancer with PSA testing, and the United States Preventive Services Task Force recommends that men should not be screened at all for the disease. But the impact of finasteride on reducing the incidence and deaths from prostate cancer and "the rest of the story" remained unanswered. At least until now.
The current research report found some interesting results:
1) With 18,880 men in the trial, fewer men treated with finasteride developed prostate cancer over the nearly two decades than those who got a placebo (10.5% v. 14.9%) (all men received regular screening using PSA)
2) Of those who did develop prostate cancer, 3.5% of those taking finasteride had high grade disease compared to 3.0% of the men in the control (untreated) group
3) Almost equal percentages of men in both groups died, implying that finasteride had no impact on overall mortality, even though it decreased the number of prostate cancers diagnosed and despite the fact that more of those cancers in men treated with finasteride were higher grades with supposedly worse prognoses
4) 10 year survival rates for treated and untreated patients with both low and high grade prostate cancers did not differ meaningfully.
Unfortunately, the researchers were not able to determine the exact causes of death for the men in the study, so we can't tell if fewer or more men in any of the groups experienced a decrease or increase in prostate cancer deaths. However, ultimately, the end result was the same: no matter the cause, finasteride didn't make a difference in how long a man lived.
So does that mean finasteride had any usefulness in patient care?
If you read the study, you would be justified in concluding, "Not really." After all, this is a drug that can have some disturbing side effects, like breast enlargement and sexual problems among others. Not a drug that most men would want to take for an extended period of time if it might have some undesirable side effects.
But if you read the editorial that accompanies the research, you might conclude that in a twisted logic sort of way, finasteride might be something a man might want to consider. Michael LeFevre is a physician who is vice-chair of the USPSTF, and was very involved in the Task Force recommendation that men should not have PSA testing. He also wrote the editorial on this current study in the New England Journal.
Dr. LeFevre in his editorial acknowledged the significant role that a prostate cancer prevention strategy could have in this country. After all, we diagnose almost 250,000 men with prostate cancer every year in the United States. Prevent some of that disease, and you have accomplished something significant. However, although finasteride did prevent some prostate cancer, it really didn't make a difference in how long a man lived. So it fails that important test.
How could the use of finasteride be valuable? If it doesn't reduce deaths from the disease, what does it do that might be meaningful in patient care?
Dr. LeFevre concludes that what it could do is decrease the number of prostate cancers found through PSA testing. If you reduce the number of cancers found, you reduce the number of men who have to be treated for the disease. And since it appears that most of the benefit of PSA testing is for finding low grade disease that might never harm a man, and that most of the harms of finding low grade prostate cancer are associated with treatment, so the logic goes, if you don't find as many less serious cancers you don't harm as many men with treatment that doesn't really offer them much benefit.
Got it? Sort of like a riddle if you think about it.
So should men start taking finasteride to reduce the chances of finding a disease that won't necessarily harm them and not have to go through a treatment that might in fact make them uncomfortable?
Not really, suggests Dr. LeFevre. In one of the more straightforward recommendations I have seen in the medical literature, he concludes:
"Men who are aware of and understand the benefits, risks, and uncertainties associated with the use of finasteride for prevention (of prostate cancer) may make a rational decision to take the drug to reduce the harm of screening. Of course, another way to reduce the harm of screening is to choose not to be screened." (emphasis mine)
Maybe it's time to put a finish to the finasteride discussion. After 18 years, it appears we can move on to other issues that are perhaps a bit more pressing--and whose logic is a bit more straightforward.
Thank you Dr. LeFevre for making a simple, straight forward recommendation the final conclusion of this saga.