If there’s a prostate in your life, or in the life of someone you love, you’ll be interested in this week’s New England Journal of Medicine (NEJM). It includes the results of two major clinical trials investigating the effectiveness of screening for prostate cancer with a blood test called PSA, prostate-specific antigen.
Prostate-cancer screening remains controversial for one simple reason: We’re not sure if it works, or if it works well enough to justify the attendant risks. The crux of the prostate cancer-screening conundrum can be gleaned from the first sentences of each of these NEJM articles.
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is being conducted by the National Cancer Institute at the National Institutes of Health. From 1993 to 2001, researchers randomized 38,000 men to either screening or no screening, and their paper opens by stating, “The benefit of screening for prostate cancer with serum prostate-specific antigen (PSA) testing, digital rectal examination, or any other screening test is unknown.” Translation: We don’t have any proof that this works. But we’re still doing it.
The second paper was from a European trial wherein half of a group of 180,000 men age 55-69 were screened every four years with PSA. The Europeans open with a different, more illuminating statement: “Measurement of serum prostate-specific antigen (PSA), a biomarker for early prostate cancer, is useful for the detection of early prostate cancer. Nevertheless, the effect of PSA-based screening on prostate-cancer mortality remains unclear.” Translation: We have a blood test that can detect prostate cancer at an earlier stage, but we’re not sure it helps people live longer.
Why wouldn’t detecting prostate cancer earlier lower mortality?
The answer to that question comes in two parts. First, prostate cancer is typically a very slow-growing, indolent cancer. Second, many men have it, but because it grows so slowly, very few will develop clinical symptoms; if they do, it will have taken years and years to get to that point.
Autopsy studies on young males show just how common prostate cancer is. In one study, 27 percent of men in their 30s were found to have small areas of cancer in their prostate gland; 34 percent of men in their 40s had small foci of cancer. The number affected rises with age, with as many as 80 percent of 80-year-olds having cancerous changes in their prostate.
So, many men will develop prostate cancer, but it takes many years to become clinically apparent, and most men who have it will end up dying of something else. Want that in numbers? According to a paper in the journal Urology, a 50-year-old male has a lifetime risk of 42 percent for developing microscopically detectable prostate, a 9.5 percent risk of developing clinically apparent disease, and a 2.9 percent risk of dying of prostate cancer.
Not “Who has it?” but “Who will develop disease?”
Because most prostate cancer is slowing growing and nonlethal, finding it earlier won’t change mortality rates. The ideal screening test would help identify those who will go on to develop clinically apparent, symptomatic disease, because those are the only men who could possibly benefit from treatment (what good is a toupee if you haven’t gone bald?). Up to this point, PSA testing hasn’t been particularly good at doing that. Dr. Joel Slaton, associate professor of urologic surgery at the University of Minnesota is well familiar with the pitfalls of screening with PSA.
“The two big problems in prostate cancer are, how do we avoid treating the low risk population, and how do we find and better treat the high risk population. That’s really what matters,” Dr. Slaton explained. “If you look at it, 180,000 people will be diagnosed with prostate cancer this year, and ‘only’ 27,000 are going to die from it. More than half of those people who are going to die have high-risk cancer, high-grade cancer, which makes up only about 15 percent of overall cancers that you identify.”
Most men with elevated PSA levels will go on to have ultrasound guided biopsies of the prostate. If cancer is found, it is graded according to how aggressive it looks. The idea is that men with low-grade cancer can be reassured, and those with high-grade cancer can go on to have treatment, generally via surgical removal or with radiation.
While most positive biopsies show low-grade cancer, the problem is that no patient is ever “reassured” by a diagnosis of cancer, not even a typically slow-growing one like prostate cancer. Most men want the cancer gone, treated, killed — associated risks be damned. Cancer of any kind has a looming quality that makes it hard to live with.
It’s this predicament — you’ve got cancer, but there’s a good chance it won’t hurt you — that makes prostate cancer specialists like Slaton eager for a “New and Improved PSA.”
“So what you want are better biomarkers, a high percentage of which will identify the high-risk cancer. So then you don’t go do biopsies on the willy-nilly to find the 15-20 percent that are high risk,” Slaton explained. “You need to find better biomarkers than PSA, or that add to PSA, not to find more prostate cancer, but to find more high risk prostate cancer.”
Treating individuals to benefit the group
What conclusions did these two studies draw? The American study found that the rate of death from prostate cancer was very low, and that screening for it didn’t seem to change that. The European study concluded that 1,410 men would have to undergo screening, knowing that 48 of them would undergo treatment, so that over a 10-year period, one of them would have his life spared from prostate cancer.
Those numbers are what make recommending PSA screening so difficult: No doctor can tell a patient whether the test is going to save his individual life, or perhaps greatly complicate it. It may help you to know that many male physicians struggle with this decision to be screened themselves.
“What you’re doing is helping a group, not an individual,” Slaton explained. “That’s why, personally, treating prostate cancer is tough, because it’s not definitive for individuals. You’re helping a group, but not necessarily the individual, so you’re treating a lot of patients to help your own group.”
Although the European study found PSA to be equal to mammography in terms of the number-needed-to-screen to detect one cancer, the difference is that breast cancer is more aggressive, more mortal. For most breast cancer types, the patient can begin treatment with a resolve that comes from knowing that her tumor cannot be safely watched. A man rolling into the operating room to have his surgery, or who is beginning radiation therapy, will wonder if he is the one out of 48 for whom treatment will be lifesaving.
Slow-growing cancer needs a long-term study
While both of the studies in the New England Journal of Medicine are large and well crafted, they are reporting interim results; each trial is ongoing. The European trial reported results through the first eight years of follow-up, the American trial for seven years. As Slaton pointed out to me, those time frames aren’t very long time for the slow-growing prostate cancer.
“That’s not a lot for prostate cancer. Usually you want 15 years, or double that, to say if you really affect prostate cancer outcomes,” Slaton told me.
Until the final results of these two screening trials (or others) become available, deciding whether to be screened for prostate cancer remains a difficult choice. An NEJM editorial recommends that individual patients make their individual choice about PSA screening by consulting with their doctor. Translation: No one really knows what is the right thing to do.
Dr. Craig Bowron is a Twin Cities internist and writer who reports on medical topics for MinnPost. He can be reached at cbowron [at] minnpost [dot] com.