Forgoing a test to detect prostate cancer could mean that three times as many men would fail to have the disease detected before it spreads to other organs, according to a paper in Cancer on July 30. This new finding arrives just months after the U.S. Preventative Service Task Force issued a recommendation against using PSA screening. The task force gave PSA screening a grade of "D," meaning it does more harm than good for most men.
The FDA approved PSA screening in 1986 as a diagnostic test to detect prostate cancer, and it has been controversial from the beginning. The screening has a high false positive rate because PSA levels rise from nonmalignant prostate growth. Additionally, many prostate cancers grow so slowly that they will never cause problems, and it is nearly impossible to tell which cancers need to be treated and which can be left alone.
Surgery or radiation used in treatment can produce incontinence or impotence. As with any surgery, there is a small risk of death or other serious complications, and it's painful, even under the best of circumstances. The task force analyzed several large studies and determined that the benefits of screening and treatment did not outweigh the risks.
The goal of the Cancer study was to determine how many cases of prostate cancer might be missed until they metastasized if PSA testing were eliminated. Metastatic prostate cancer, a malignancy that has spread to distant organs, is usually symptomatic, leading men to seek treatment. It's generally fatal within a few years. Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program to determine the prevalence of men who were diagnosed with metastatic prostate cancer as their initial prostate cancer diagnosis, rather than a less invasive form.
The researchers used data from 1983 to 1985, the three years immediately preceding the PSA screening test, to determine the rate of metastatic prostate cancer cases without screening and used the rate to extrapolate the number of cases in 2008, the latest year for which data are available.
They then compared the expected rates to the actual rates for that year and calculated that approximately 25,000 men would have been given an initial diagnosis of metastatic prostate cancer in 2008 without screening, as opposed to the approximately 8,000 who did.
Edward Messing, the senior author of the study, says that PSA is capable of detecting the disease earlier, which could, in theory lead to fewer deaths from prostate cancer. Marc Garnick, a prostate cancer expert at Harvard Medical School, points out, "this would have been a much more powerful study if they had mortality outcomes, not the incidence of metastatic disease."
In fact, Garnick says the clinical trials that have addressed mortality rates have already been done, and they indicate no difference in overall survival or prostate cancer survival in men who underwent screening. Studies like Messing's, he says, are trying to poke holes in the research. "Every single time these studies come out, the backlash is that the studies were flawed. I'm not aware of any program in medicine where randomized studies posed in prestigious journals come out with these negative conclusions, and everyone is trying to data mine the conclusions. It's unprecedented."
Garnick says that PSA screening is based on the faulty assumption that cancer starts small, becomes localized in the prostate, advances to nearby regions of the body, becomes metastatic, and then kills. If this were the case, screening studies should have showed that more lives were saved. "The screening studies show that there's no difference in mortality. The biology of the cancer trumps the stage of the cancer."
In addition, the largest difference between expected and observed metastatic cancer is in older age groups. "The headline seems to be coming from patients who are greater than 80 years old," Garnick says. But those patients often have many other health problems that lead to death before even aggressive prostate cancer.
Otis Brawley, a medical oncologist and chief medical officer of the American Cancer Society who was not involved with the study, says, "It certainly adds to the body of evidence, but it's by no means definitive." One problem is that many men whose initial diagnosis is localized, not metastasized, prostate cancer, end up relapsing even after having their prostate is removed. This means that the cancer had already metastasized by the time of the first diagnosis, but it could not be detected at that time. Those patients already had metastatic disease when screened, but they were not diagnosed at the time, and so they are not counted in Messing's study.
Another problem is that modeling studies, like this one, are inherently less powerful than other kinds of medical research: randomized clinical trials, the gold standard in medical research, in which patients are randomly assigned different treatments or no treatment; case-control studies, which compare patients who have a condition with those who do not; or cohort studies, which determine the risk of contracting a disease by studying a group of people with similar demographics. So the results from a modeling study, no matter how compelling, are not definitive. They should lead to other studies, and eventually clinical trials.
On both sides of the debate researchers agree that men should be informed of the risks and possible benefits of PSA screening and subsequent treatment before they start the process, a challenge when contradictory reports abound. Garnick says, "My heart goes out to both patients and physicians because the whole concept of screening, diagnosing and offering treatments is among the most complicated in medicine."
"What we need is a better biomarker that not only tells us that the patient has cancer but what the behavior of that cancer is likely to be," Garnick continues. "It becomes a circular argument until we get better biomarkers." For now, men and their families have to make tough choices about whether knowledge is power or ignorance is bliss.