After twenty years, what began as a hunch about prostate cancer has turned into a remarkable breakthrough.
News this week that billionaire investor Warren Buffett intends to undergo radiation therapy for early-stage prostate cancer has refocused the nation's attention on a curious and perplexing disease. At 80, Buffett's chance of dying from prostate cancer as opposed to something else is fairly low -- prompting some to wonder if he'd be better off avoiding treatment altogether.
The uncertainty surrounding Buffett's diagnosis is a perfect example of how little we still understand the prostate. Back in 1993, Charles Mann penned a lengthy story for The Atlantic called "The Prostate-Cancer Dilemma," in which he explained how scientists came to understand the causes behind prostate enlargement, a related but benign condition:
[Benign prostate hyperplasia, or BPH] is linked to the presence of male hormones, especially testosterone, and male hormones are necessary to maintain interest in sex. Past efforts to treat the condition without surgery involved blocking the effects of testosterone, which risked eliminating a man's libido.
That was before researchers discovered that prostate enlargement -- an affliction that puts pressure on the bladder and makes it hard for men to urinate -- was due to a very specific kind of testosterone called dihydrotestosterone, which itself was the product of a prostate secretion known as 5-alpha-reductase. Treating BPH medicinally, then, meant blocking the effects of 5-alpha-reductase -- and soon, the pharma company Merck was selling a drug called finasteride that could do it. (Incidentally, finasteride is sold under two brand names. Proscar is the one that targets BPH. The other comes in the form of a little hair-loss remedy called Propecia.)
Near the end of his article, Mann referenced a major longitudinal study on finasteride that at the time was just getting underway. Citing lab tests that appeared to link 5-alpha-reductase not just to prostate swelling but to prostate cancer, Mann speculated that taking finasteride could someday become a viable way to actually prevent prostate cancer from ever occurring.
All the back-and-forth over Buffett's cancer -- and that of the more than 240,000 other men who will be diagnosed with it this year -- raises one, big question: where did that trial end up?
In 2003, researchers suspended the trial early, for seemingly positive reasons. They managed to prove almost decisively that finasteride did cut down on the incidence of prostate cancer. But what they didn't realize until much later was that those who did eventually contract prostate cancer tended to be serious cases. In other words, finasteride did very little to curb prostate cancer rates among those who really needed the drug to work, while putting a greater burden on the healthcare system to treat low-grade cancers that could have safely been left alone. Hardly an ideal outcome.
Fortunately, newer analyses of the same study (which involved 19,000 men in the largest prostate cancer prevention trial to date) show that these conclusions were wrong. In fact, said Dr. Ian Thompson, some of the low-grade cancers that researchers thought were irrelevant turned out to be kind of important:
"We've now shown that the cancers prevented by finasteride are often clinically significant, the same kind of cancers that lead to surgery," said Thompson. "In addition, we showed a 28 percent reduction of high-grade cancer with finasteride."
What can we learn from this episode? Well, for one thing, revisiting old data with fresh eyes can give rise to new breakthroughs. But more importantly, the link between 5-alpha-reductase and prostate cancer appears to exist, as we thought. And we may already have the drugs to exploit it.
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