Experts Face Off on Prostate Cancer Drugs

If you could prevent a disease, especially one as scary as cancer, by taking a drug, would you do it? Most likely, yes.

That's exactly what drugmaker GlaxoSmithKline (GSK) thinks men who are at increased risk for prostate cancer should do -- take its Avodart, generically known as dutasteride, to reduce their risk of getting the disease.

Prostate cancer is the most common cancer found in American men, other than skin cancer, and is the second-leading cause of cancer death in men.

Another common condition for men as they age is an enlarged prostate gland, but that's a noncancerous condition. Technically, it's called benign prostatic hyperplasia (BHP), and it doesn't lead to prostate cancer, although a man can have both conditions. Depending on the severity of the symptoms, the treatments for BPH range from watchful waiting to surgery and drugs such as GSK's dutasteride or Merck's (MRK) Proscar, generically known as finasteride, which shrink the prostate.

Cuts Cancer Risk, but...

Two years ago, a study found that when taken as a preventive measure, finasteride cut the risk of prostate cancer by a quarter in healthy men, but it also found that the tumors detected were more aggressive. GSK conducted a similar four-year, international, placebo-controlled, randomized study that showed its dutasteride cut the risk of prostate cancer by 23% -- not a trivial reduction.

"The disease is an ideal target," wrote Dr. Patrick Walsh in an editorial in the April 1 issue of The New England Journal of Medicine, which published the research. "If we could prevent the disease or delay its progression, many men could be spared the burden of diagnostic procedures and treatments, and costs to the health-care system could be reduced substantially."

Yet many medical professionals, including Walsh, don't think it's a good idea to prescribe the drug widely as a preventative treatment. While the scientific reasoning behind the tests of dutasteride -- which blocks hormonal stimulation of the prostate -- is sound, Walsh raises several issues regarding the study and its conclusions.

Which Data to Believe?

Prostate cancer is relatively slow-growing, and often not lethal. Many doctors prefer the watchful-waiting approach when the cancer is in its earliest stages and shows slow progression.

Walsh questions whether the cancers prevented by dutasteride were actually clinically significant. Though the study does show that the drug led to a significant reduction in low-grade prostate cancers, there wasn't a significant reduction in the high-grade prostate cancers that are more likely to be lethal. That's disappointing, Walsh writes.

However, the study's lead author Dr. Gerald Andriole, chief of urological surgery at Washington University School of Medicine, responds that this is true only when looking at the raw data. When the data are adjusted, "there is a significant 38% reduction in high-grade tumors among men in the dutasteride arm."

Moreover, he says, while watchful waiting is a sound approach in many cases, "In reality, in the U.S., it has been estimated that between 80% and 90% of men diagnosed with prostate cancer end up with aggressive treatment" that can leave them impotent or incontinent. With over 27,000 deaths a year from prostate cancer despite aggressive treatments, this shouldn't be surprising.

Yet another concern arising from the study was an increase in heart failure among those taking dutasteride. This, GSK and the researchers say, was quite unexpected, inconsistent with earlier studies and could be related to the alpha-blocker drugs some of the patients were taking. "This deserves further study," Andriole said.

False Sense of Security or Improved PSA Testing?

Finally, Walsh questions the conclusion of the study. Unlike the researchers, he believes the drugs only temporarily shrink tumors that have a low potential for being lethal, but don't actually prevent cancer.

Furthermore, while the drugs indeed treat prostate condition symptoms successfully by shrinking the gland and reducing the prostate-specific antigen levels (PSA is a marker that can point to cancer), as a preventive measure he worries the low PSA levels could lull the men into a false sense of security, which could end up leading to worse problems later.

Andriole disagrees with this as well. "The major problems with screening for prostate cancer using PSA . . . is what has been referred to "overdiagnosis" and "overtreatment," he notes. As well as preventing BPH-related problems, "both finasteride and dutasteride actually improve the ability of PSA [tests] to detect the most aggressive cancers," a desirable outcome of the study that will be reported in a later paper, and one that could reduce the chance of overdiagnosis. Instead, he recommends that PSA tests be used differently for men on the drugs, adjusting for the expected lower levels shown in patients taking dutasteride and finasteride.

If the Experts Can't Agree ...

Many men who are worried about prostate cancer will probably be happy to hear that they may be able to do something to reduce their risk. Others may be skeptical of any study that seems designed mainly to expand drug sales; they may be more inclined to listen to those questioning the results.

Either way, men are left smack in the middle of experts' differing opinions. As always, the best thing to do is to discuss treatment options with your own doctor.