Playing the blame game for rising prostate cancer rates

Blame the rising rate of prostate cancer on better testing. Blame it on the ubiquity of the disease as men age. Just don't blame it on the pathologists. They feel bad enough.

Better detection of prostate cancer means that diagnosis has become inevitable in most men if they live long enough, reported Oliver Sartor, MD, of Tulane University, at Internal Medicine 2008. The good news is that better detection may have led to fewer deaths, although there is continuing controversy over why.

Art 1 Improved detection led to a higher “incidence rate” of prostate cancer starting by 1992, said Dr. Sartor, a professor of cancer research in the departments of medicine and urology at Tulane, who led two sessions on “Controversies in Prostate Cancer: Screening, Evaluation of the Rising PSA, and Effects of Anti-Androgen Treatment.”

Autopsy results show that more than half of men over 50 have prostate cancer. Clinically, about 17% of men over age 50 are diagnosed with it and about 3% die from it. (Despite the impact of early diagnosis on lowering mortality, prostate cancer is the second-leading cause of cancer death in men, behind lung cancer.)

A comparison of transurethral resection of the prostate and biopsy detection among more than 18,000 men with normal prostate-specific antigen (PSA) levels and digital rectal exam (DRE) results—”a low-risk group”—showed that 25% of that population had prostate cancer [N Engl J Med. 2003;349:213-22].

“A lot more men have the disease than are ever destined to die from it,” Dr. Sartor said.

Art 2 Abraham Morgentaler, MD, a urologist at Beth Israel Deaconess Medical Center who led a separate session on “Men's Health,” noted that 80% of men at age 80 would test positive for prostate cancer if their prostates underwent serial sectioning.

“The more you look for prostate cancer, the more prostate cancer you will find,” Dr. Morgentaler said.

When to screen?

Better testing became available in 1988-89, when PSA was initially used as a tumor marker in men previously diagnosed with prostate cancer, Dr. Sartor said. In 1991, the first of a series of papers demonstrated that PSA might serve as a test for early detection [N Engl J Med. 1991 Apr 25;324(17):1156-61].

More and more biopsies became PSA-driven as widespread screening began in 1992-93. Increased early detection using PSA dramatically increased prostate cancer rates, a kind of ascertainment bias that has since leveled off, Dr. Sartor said.

About seven years after the onset of PSA screening, death rates from the disease began to decline in the U.S. It is controversial as to whether this represents increased effective treatment of early detected prostate cancer or more effective treatment of disease recurrence, Dr. Sartor said.

If prostate cancer is ubiquitous, what is the role of screening?

The U.S. Preventive Services Task Force says that evidence is insufficient to recommend for or against screening using PSA and DRE. The American Cancer Society suggests that PSA and DRE should be offered annually to patients beginning at age 50 for men with a life expectancy of 10 or more years.

Art 3 Screening is useful because it reduces mortality, according to Dr. Morgentaler. During his residency in the mid-1980s, he said, prostate cancer diagnoses were 75% metastatic and 25% localized. As recently as five years ago, those figures had reversed, and today the rate of metastatic cancer has fallen even lower than 25%.

Urologists use a PSA of 2.5 ng/mL as a threshold for merits of a biopsy, Dr. Morgentaler said. Most non-urologist physicians in favor of PSA to trigger a biopsy still use 4.0 ng/mL. Either is a defensible standard of care, he added.

Both Dr. Sartor and Dr. Morgentaler said the change in PSA is more important than the absolute value. If you screen a man for years at 1.0, 1.1 and 1.2 ng/mL and then find a value of 2.6 ng/mL, that signals caution, Dr. Morgentaler said, as would symptoms such as trouble voiding the bladder, voiding with more frequency or having to urinate in the middle of the night.

A practical solution to sudden increases is to try to resolve any inflammation with two weeks of quinolones and re-do the PSA. A biopsy should only follow if the PSA remains elevated. The only failure is to not follow up on testing, Dr. Morgentaler said.

“If you order that test, the greater community will see you as responsible for the results of that test and expect you to act appropriately,” he said.

When to treat?

If all men will eventually have prostate cancer, then at what point is it appropriate to move from diagnosis to treatment? In recent years, the medical community has become much more comfortable with surveillance over treatment, Dr. Morgentaler said.

Urologists and oncologists are becoming more comfortable with surveillance as an option—a change from a previous “knee-jerk” reaction to treat every case. A few studies of surveillance so far suggest, albeit not conclusively, that there is little added mortality, and Dr. Morgentaler added about one-third of men will continue on from surveillance to treatment within several years.

Dr. Morgentaler cited a pathologist at his facility who once fretted over the biopsy of a prominent Boston-area patient. Dr. Morgentaler asked about the lab results, and said the pathologist replied, “It looks like cancer, but if I call it cancer, you're going to take his prostate out, and he'll become impotent and incontinent, and his wife will never forgive me.”

So please don't blame the pathologist for the diagnosis of prostate cancer. The take-home message, Dr. Morgentaler concluded, is PSA screening diagnoses some men with prostate cancer who would otherwise have never had trouble from it. But it's also saving lives of men who would have died prematurely from prostate cancer by diagnosing it at an earlier, more curable stage.