A

n analysis of two influential studies of prostate cancer screening concludes that the much-debated test “significantly” reduces deaths from the disease, suggesting that current recommendations against routine PSA screening might be steering men away from a lifesaving procedure.

The analysis, published Monday in Annals of Internal Medicine, drew wildly different reactions, as is often the case with research on PSA screenings. Some experts in cancer screening and statistics said its novel approach was “on shaky ground” and used a “completely unverifiable” methodology that they had “never seen before,” but others praised its “intriguing and innovative approach.” There was one area of agreement, however: “I imagine it’s going to generate some buzz,” said biostatistician Ted Karrison of the University of Chicago.

If the new analysis is correct, one of the influential PSA studies, called PLCO, reduced deaths from prostate cancer by 27 percent to 32 percent, not the zero percent that PLCO researchers themselves found. For a man in the U.S., the risk of dying of prostate cancer is about 2.5 percent. A mortality reduction of 30 percent would lower the death rate to 1.75 percent, said epidemiologist Ruth Etzioni of Fred Hutchinson Cancer Research Center, the study’s senior author.

advertisement

“If a screening test reduces cancer mortality by 20 percent, it’s considered a successful test,” Etzioni said. “I think the [prostate-cancer] mortality reduction we calculate is a significant benefit. This is a screening test that saves lives.”

Those gains come at some cost to health, though: For every life saved, she estimated, five men will be told they have cancer when in fact their abnormal cells would never grow, spread, or harm them. In other estimates, such “overdiagnoses” outnumber lives saved by 50-to-1.

The new study lands amid another shift in how experts view PSA screening, which measures blood levels of a molecule sometimes associated with prostate cancer. In 2012 the U.S. Preventive Services Task Force, whose recommendations help determine that procedures insurance should cover, recommended against routine PSA tests because of their many risks and tiny benefits. Among other drawbacks, the tests lead to overdiagnosis (meaning a biopsy finds malignant cells but they are so innocuous they would never harm, let alone kill, the man) as well as incontinence and impotence from treatment (including of harmless cancers).

In April, however, the task force proposed instead that men aged 55 to 69 discuss PSA’s pros and cons with their doctor and then decide what to do, factoring in that if 1,000 men get regular PSA screening for a decade it will save about one life. (Older and younger men are still advised not to have routine screening.)

The rationale for the re-analysis led by Etzioni is that the PLCO study was a bit of a mess. It assigned half of its nearly 77,000 participants, men ages 55 to 74, to have yearly PSA tests and the other half to not do so. But 46 percent of the men in the no-PSA group had yearly PSAs anyway. As a result, when researchers counted deaths in each group, it wasn’t a clean comparison: Rather than comparing screened to unscreened men, they were comparing assigned-to-screening men to not-assigned-to-screening men.

The finding that assigned-to-screening men were no more likely to avoid death from prostate cancer might therefore have been because their screening behavior wasn’t different enough from the “unscreened” (but in fact partly screened) men’s, not because PSA screening doesn’t save lives.

In an effort to untangle that possibility, Etzioni and 21 co-authors from 10 countries created multiple mathematical models. They all rely on estimates of “lead time,” or how much sooner a cancer is detected because of PSA instead of because symptoms are detected. The models incorporated the records of all the PLCO men and ignored which group they’d been assigned to.

Newsletters

Sign up for our Morning Rounds newsletter

Please enter a valid email address.

Bottom line: Screened men’s cancers were detected earlier than unscreened men’s, and more frequent screening advanced detection more. That moved some prostate cancers from too-advanced-to-treat to treatable, reducing prostate cancer mortality by 27 percent to 32 percent over 11 years, Etzioni and her colleagues conclude.

Researchers not involved in the study weren’t convinced. “The concern is that men in the no-screening group but who chose to get screened anyway might differ in important ways from men who stayed with no-screening,” Karrison said. They might be more health conscious or conscientious, or have other traits associated with longevity. If so, then those traits, not screening, might be responsible for their lower risk of dying from prostate cancer. Two prominent experts in cancer prevention and statistics agreed, but said they did not want to be publicly identified as criticizing the new analysis because some of its authors are colleagues of theirs.

Dr. Kenneth Lin of Georgetown University Medical Center, a former staffer at the USPSTF, said crediting PSA tests with reducing prostate cancer mortality by around 30 percent was probably an overstatement, especially since mathematical models are only models. An earlier one for the PLCO study concluded that more men died in its screening group than in the don’t-get-screened group. “Models are models,” Lin said. “No matter how sophisticated, they shouldn’t trump data from real people who participated in the randomized trials” — which in PLCO found zero lives saved from PSA screening.

A researcher associated with the Preventive Services Task Force, but who was not permitted to speak to reporters while the group is finalizing its PSA recommendation, said the panel would incorporate the new paper in its analysis. “But honestly,” he said, “I don’t know that this adds a great deal to our understanding.”

Leave a Comment

Please enter your name.
Please enter a comment.

  • Great summary of a muddled story. If I make a decision to have a major medical procedure with lots of potential complications, it would be based on hard research, not mathematical models of possibilities.

  • “the risk of dying of prostate cancer is about 2.5 percent. A mortality reduction of 30 percent would lower the death rate to 1.75 percent”

    That’s a huge exaggeration even if the 30 percent reduction is true. The 30 percent reduction only applies to men in the core screening age group of 55-69. Once men become older than this range (when the vast majority of prostate cancer deaths occur), this reduction no longer applies. Accounting for this fact means the total prostate cancer mortality might be reduced to 2.4 or 2.3 percent.

  • I believe that it makes sense to have PSA tests, and then think about what steps to take if the PSA level has a high trend or if PSA exceeds acceptable levels.

    However, the method used in the recent analysis is clearly flawed. Patients are randomized to avoid the self-selection that occurred as members of the control group had treatment. That being said the original study, which showed no significant difference, was also clearly flawed because they were not making a clean comparison to a control group.

    • After you get a PSA-positive is not the time to start thinking about what to do do if you get a PSA-positive. You should start thinking about what to do as soon as you decide to get screened at the very latest. Any sort of emotional distress and time-constraint is a terrible environment in which to think about these things.

  • I am suffering from Prostate Cancer last Feb. 2012. I want to know how cure prostate cancer of my which therapy we use . Please. Give me sugestion
    .

    • Dr. Khera, please find the Facebook Prostate Cancer Forum, and also go to jimjimjim (dot) com for more information on treatments — by patients, for patients. Google “offical prostate cancer treatment protocol PDF” for the official treatment guidelines by the medical community, based on the science. Turn to the forums for additional, but not replacement, therapies and treatments to enhance your quality of life during and after treatments. God bless you. Dr. Rings

  • My best friend died from prostate cancer at 46.

    Never screened. PSA can save lives. The only drawback is the Medical Industrial Complex desire to cut costs.

    Men, get screened!

  • African-Americans get little consideration in test elimination proposals. I know several men with no symptoms who had Stages 2 – 4 of prostate cancer that was only discovered through a PSA test and subsequent biopsy. Some were under age 60. Thankfully, they are all alive today.

  • Get checked! It saved my life. Found it in a life insurance checkup. Had no signs of anything wrong. Side effects, sure but I’m alive.

    • “It saved my life.”

      No one can know if PSA screening saved their life. It is not possible to know what would have happened otherwise. Doesn’t stop people from claiming they “know” of course. Even trials have been completely unable to show there is even a disease-specific mortality benefit up to 7 years after screening.

  • I am now age 54 with metastatic prostate cancer. My PSA at age 50 was 0.5, then at 52, 1.1, then age 53 it was 2.5 (still normal range, normal digital rectal exam). My primary care doc said don’t worry, it’s still in the normal range, no more testing until next year. Within 10 months I started having nocturia and hermatospermia. DRE normal, PSA rechecked…now 90! Metastatic spread to bones, abdominal lymph nodes and one node so large it is causing kidney damage before the urologist put in a stent.
    Men: ignore the “stats” and demand a baseline PSA around 45-50, and get a biopsy or CT scan of the abdomen/pelvis if it doubles or quadruples. Once it is outside the prostate, mortality increases significantly, and treatment options get more difficult (think chemo and lifelong castration meds).
    Forget the “normal” range (PSA<4) if it increases 2x-4x, and especially if you take Propecia for male pattern baldness…it can artificially suppress your PSA, which most docs don't take into consideration at all (I only found this information out too late).
    Demand your health care you want, and demand a PSA, AND THOUGHTFUL ANALYSIS OF THE TRENDS OVER TIME.

  • Dr follow guidelines that govt sets except for some dr. Our dr did not worry about my husbands PSA chg of 2013 1.5 to 3.5 in 2014. Dr at kaiser said does not mean anything. Do digital exam for over 20 years. Dr said never found any cancer that way. New dr said well what would you do if PSA goes high? No need to check. 1 1/2 yr ago had MRI and Ct for back said dr should order bone scan. Asked him and family dr. Both Dr said not needed lymph gland were enlarged nothing to worry about. We asked about follow up he said not needed. Few mo ago went to dr as burn with urination and hard to pee. Thought just enlarged prostate. Well had large tumor and cancer had spread to more lymph glands and spine possibly to cervical neck. PSA was over 29 Now doing hormone therapy to keep it from spreading more. Dr said it is systemic and could be anywhere in body but not yet big enough to show up yet. No cure just keep at bay. Now they say discuss only with men bet 55-69. Bull s—
    In 2012 govt recommend no PSA tests. Too many biopsy and cost. We had friend we had biopsy twice before they found his cancer and he died of it. That is like saying do not biopsy breast cancer as it may be negative do not hear about that. I had 2 breast biopsy and glad I did negative thank goodness but if not done and positive I would be in same shape as my husband is. Govt will not test things like marijuana or other natural cures as the pharmacy companies pay everyone off as they would not make money. If they find something like a recent PSA medicine had 2 great studies. Will take years to be approved by FDA. Cost ? $9000 per month. What about the guy who bought a RX co that was selling life saving pills for $5 he raised it to $500+. Same epipens sky high rise. This is price gouging. Govt plays with our health and now my husband is paying for it. Trying to do our own research. Do not trust doctors but due to cancer have no choice. Thanks for your great article.

    • It’s not the government that recommended against testing, it is the medical societies.

      Most men eventually get prostate cancer. Some is fast acting; that is the kind that kills people. Other prostate cancer is slow acting and relatively benign. People with fast acting prostate cancer should have aggressive treatment. People with slow acting prostate cancer are probably better off if they are closely monitored without having aggressive treatment. That being said, it makes sense to me to have a PSA test, and then decide what to do if the PSA test is positive.

Sign up for our Morning Rounds newsletter

Your daily dose of news in health and medicine.

X