September 4, 2017
For men who are weighing the pros and cons of prostate cancer screening, a new study strengthens the evidence that testing can reduce deaths from this cancer, something two earlier large landmark clinical trials appeared to reach different conclusions about.
The findings do not resolve many of the questions that remain about prostate cancer screening, since routine testing can lead to unneeded and potentially harmful treatments in men who do not need it. But it provides more information that experts can use to assess the benefits and risks of screening.
One of the earlier trials, conducted in Europe, found that screening reduced deaths from prostate cancer by 21 percent, though it led many men down a bumpy road toward harmful or even unnecessary interventions. The other trial, based in the United States, found no difference in death rates between men who were randomly assigned to screening and those who were not. Both reports were published in 2009 in the New England Journal of Medicine.
For the new paper, published Monday in Annals of Internal Medicine, a broad consortium of scientists, including some of the investigators in the original studies, reanalyzed the data from the two trials using three different mathematical models. When they made a rigorous comparison between death rates among men who had actually undergone screening and men who had received no screening, the researchers concluded that screening tests reduced prostate cancer deaths by 25 to 32 percent. The reduction was primarily a result of the earlier detection of cancer, the researchers said.
“By the time the U.S. trial started, a lot of the population was already being screened for prostate cancer” as part of routine care in their doctors’ offices, said Ruth Etzioni of the Fred Hutchinson Cancer Research Center, the senior author of the new paper. About three-quarters of the men in the group that were in the comparison group that was not assigned to screening in the trial were still tested as part of their regular medical care, she said.
Meanwhile, some men assigned to the trials’ screening groups did not actually get screened, further muddying comparisons between the two groups, she said.
“Comparing the groups to one another wasn’t answering the question everyone really wanted answered,” Dr. Etzioni said. “What our analysis amounts to is the comparison that people really wanted: screening versus not screening.” (The Annals provides a summary of information for patients on its website.)
Several investigators from the earlier trials, who made their records available for the new analysis, are also authors on the new paper, and scientists involved in the American trial, which goes by the acronym PLCO, said the analysis was an important contribution.
Screening for prostate cancer is typically done using a blood test that measures levels of a protein released by the prostate gland called prostate-specific antigen, or PSA, which may indicate the presence of prostate cancer when elevated. But increased levels can also be caused by less serious medical conditions, like inflammation.
The new analysis doesn’t resolve the dilemmas surrounding choices about prostate cancer screening. While prostate cancer is one of the most common cancers affecting men and it can be aggressive, many men have a slow-growing form of the disease that will likely never become life-threatening, and would not even know about it if not for screening.
More patients with these low-grade cancers are now being closely monitored by doctors instead of undergoing surgery and radiation, treatments that can lead to serious complications such as incontinence and impotence.
The aim of monitoring, or active surveillance as it is called, is to prevent unneeded treatment, said Dr. Etzioni, who does research on the harms of screening as well. “On average, in the screened population, more men will be over-treated than have their lives saved,” Dr. Etzioni said.
In its most recent draft of recommendations issued in April, the United States Preventive Services Task Force urged older men to talk to their doctors about the benefits and risks of prostate cancer screening and make an individual decision that is right for them. That’s a change from the earlier guideline issued in 2012, which told men who were not at increased risk to skip routine screenings altogether. The task force could massage the recommendation further over the next few months before issuing a final version.
Andrew J. Vickers, an attending research methodologist at Memorial Sloan Kettering Cancer Center, who wrote an editorial accompanying the new paper, said in an interview that there really is no doubt that PSA screening can curb the death rate from prostate cancer. “The debate shouldn’t be to screen or not to screen, but how can we change screening so it does not cause harm,” Dr. Vickers said.
“It’s not a take-it-or-leave-it,” Dr. Vickers said. “A PSA test cannot really harm you or save your life. What can harm you is if the test leads you to get treatment you don’t need, and what can save your life is the PSA test that finds the cancer that could kill you.”
Critics of screening say the new analysis does not change much in the calculation of risks versus benefits of screening. Only 3 percent of men die of prostate cancer, so the benefit of screening, in the number of prostate cancer deaths averted, is small in absolute terms.
Some critics of screening expressed skepticism about the new analysis, however.
“I personally believe that results from models are less convincing than data from actual clinical trials, so I doubt there’s anything here that would move the needle on PSA screening,” said Dr. Kenneth Lin, an associate professor of family medicine at Georgetown University Medical Center.
The potential harms from screening “haven’t changed, and the magnitude of benefit is small,” said Dr. Lin, a member of committee that has been reviewing the United States Preventive Services Task Force recommendations for the American Academy of Family Physicians, which advises against routine prostate cancer screening.
Men who have a family history of prostate cancer or any symptoms of the disease should be screened, experts say, as should older African-American men, who are at higher risk for prostate cancer. For other men aged 55 to 69, the trade-offs between potential benefits and harms of screening are a close call. The Preventive Services Task Force recommends men 70 and older forgo screening.
“I think the main message is that this is a choice,” said Dr. H. Gilbert Welch, professor of medicine at the Dartmouth Institute, who says he believes very few men are helped by the test. Still, he said, “There’s no single right answer to this one.”