U of M is the largest site for this national prostate cancer screening trial with 17,099 men participating

MINNEAPOLIS/ST. PAUL (March 18, 2009)— Six annual screenings for prostate cancer led to more diagnoses of the disease, but not fewer prostate cancer deaths, according to a new major report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The results appear online today in the New England Journal of Medicine (NEJM).

"What this report tells us is that the short-term benefits of prostate cancer screening, using present methods, do not result in the reductions in death that we had hoped," said Timothy R. Church, Ph.D., professor in the University of Minnesota's School of Public Health and cancer researcher with the University's Masonic Cancer Center.

Church is the principal investigator for the University of Minnesota's PLCO trial site, which enrolled 17,099 men, making it the largest of 10 sites in the United States. He also is a co-author on the NEJM article.

"It is possible that prostate cancer screening may produce longer-term benefits, and we will continue to monitor men in this study with the hope that we eventually will see reduced death from this disease," Church said. "In the meantime, it is important to remember that men differ in their risks for prostate cancer based on their family and personal history. Those men who are concerned about their prostate health should consult with their physicians about the best way to proceed."

The U.S. Preventive Services Task Force, whose recommendations are considered the gold standard for clinical preventive services, recently concluded that there is insufficient evidence to assess the balance of benefits and harms for prostate cancer screening in men younger than age 75 and recommended against prostate cancer screening in men age 75 and older.

Church said it is too early to know whether these PLCO trial results will alter the screening recommendations.

There were 76,693 men in this PLCO trial. Of the total study participants, 38,343 were randomly assigned to be offered annual screening with prostate-specific antigen (PSA) tests for six rounds and digital rectal physical exams (DRE) for the first four rounds. The other 38,350 men were randomly assigned to usual-care and did not receive recommendations for or against annual prostate cancer screening.

Of the men in the group who were offered annual screening, 85 percent had PSA tests and 86 percent had DREs. Men in the screening group were referred to their physician or health care provider for follow-up testing for prostate cancer if their PSA level was greater than 4.0 nanograms per milliliter (ng/mL) or if DRE found an abnormality.

Men in the usual-care group sometimes had these tests as well, due to the growing public acceptance of such screening. Screening by PSA in this usual-care group increased from 40 percent at the beginning of the study to 52 percent of men by the last screening year, and screening with DRE ranged from 41 percent initially to 46 percent by the last screening year.

The National Cancer Institute (NCI) began the PLCO trial in 1992 to provide answers about the effectiveness of prostate, lung, colorectal, and ovarian cancer screening tests in reducing deaths from these cancers. Christine Berg, M.D., is the NCI leader of the PLCO trial and the senior author on this report on prostate cancer screening.

The data are being made public now because the trial's Data and Safety Monitoring Board, an independent review committee that meets every six months, saw a continuing lack of evidence that screening reduces death due to prostate cancer as well as clear evidence that screening causes men to be treated unnecessarily. Today's results in the online NEJM coincide with presentation of the data at the European Association of Urology meeting in Stockholm, Sweden. (The print version of the results will appear in the March 26, 2009 issue of NEJM.)

The online publication of the NEJM also contains a report from the large European Randomized Study of Prostate Cancer (ERSPC), which shows a 20 percent reduction in the rate of death from prostate cancer but with a high risk of overdiagnosis. In the ERSPC, unlike the PLCO trial, men were referred for follow-up testing if their PSA level was 3.0 ng/mL or higher and were also screened, on average, every four years as opposed to annually PLCO.

In addition to Church and Berg, researchers on this study included Andriole GL, Grubb RL, Buys SS, Chia D, Fouad MN, Gelmann, EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, Crawford ED, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, and Gohagan JK.

More about this prostate cancer screening report

This report includes data for all participants seven years after they joined the trial and for 67 percent of participants 10 years after they joined the trial. Other important findings include:

• At seven years, 22 percent more prostate cancers were diagnosed in the screening group (2,820 men vs. 2,322 in the usual-care group). This excess is continuing to be observed in data collected up to 10 years (currently a 17 percent excess, 3,452 men vs. 2,974 men). It has long been suspected that many prostate cancers are never diagnosed and these findings confirm that suspicion.
• The vast majority of men in both groups who developed prostate cancer were diagnosed with relatively early stage II (out of IV stages, of which IV is the late stage) disease, and the number of late-stage cases was similar in the two groups. However, men in the usual-care group had more prostate cancers that fell into the Gleason scoring system's 8 to 10 range, which marks them as more aggressive. There is still some chance that the smaller number of men with prostate cancer with a Gleason score of 8 to 10 in the intervention group will lead to a mortality difference between men in the two groups, but data analyzed so far do not show any trend toward such a difference. (The Gleason scoring system was developed by the late Donald Gleason, M.D., a University of Minnesota Medical School faculty member.)
• Men in both groups who were diagnosed with prostate cancer at the same stage received similar treatments for their disease. This reflects the PLCO study design policy of not mandating specific therapies.
• At seven years, 50 deaths were attributed to prostate cancer in the screening group and 44 deaths were in the usual-care group. Through year 10, there were 92 prostate cancer deaths in the screening group and 82 in the usual-care group. The difference between the numbers of deaths in the two groups was not statistically significant. Thus there was no detectable mortality benefit for screening vs. usual-care.

A Q & A on the prostate screening results from the PLCO is available at http://www.cancer.gov/newscenter/pressreleases/PLCOprostateResultsQandA.

---

Masonic Cancer Center, University of Minnesota is part of the Academic Health Center. It is designated by the National Cancer Institute as a comprehensive cancer center for cancer research, treatment, and education. For more information, visit www.cancer.umn.edu or call 612-624-2620.

For more than 60 years, the University of Minnesota School of Public Health has been among the top accredited schools of public health in the nation.  With a mission focused on research, teaching, and service, the school attracts nearly $70 million in sponsored research each year, has more than 100 faculty members and more than 1,300 students, and is engaged in community outreach activities locally, nationally and in dozens of countries worldwide. For more information, visit www.sph.umn.edu. The School's Centers for Public Health Education and Outreach promotes lifelong learning to bridge academic and public health practice communities.

Media Contacts:

Mary Lawson, Masonic Cancer Center, University of Minnesota, 612-624-6165, mlawson@umn.edu

Sara Martin, Academic Health Center, 612-626-7037, buss@umn.edu