Prostate cancer: National study shows no early benefit from annual screenings

Clinic part of major national study

Douglas J. Reding, M.D.

Prostate cancer screenings, done annually for six years, led to more diagnoses of the disease but no fewer prostate cancer deaths, according to a major new report from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

“What this report tells us is that despite finding more tumors, men diagnosed with prostate cancers didn’t live longer,” said Oncologist/Hematologist Douglas J. Reding, M.D., PLCO principal investigator at Marshfield Clinic.

Clinic is research site

Marshfield Clinic is one of 10 research sites nationwide for PLCO, a large-scale clinical trial designed to provide answers about cancer screening effectiveness.

PLCO, sponsored and run by the National Cancer Institute’s Division of Cancer Prevention, began in 1992 to determine whether certain screening tests can help reduce deaths from prostate, lung, colorectal and ovarian cancer.

The underlying rationale for the trial is that screening for cancer may enable doctors to discover and treat the disease earlier.

Research results appeared online Wednesday, March 18, in the New England Journal of Medicine (NEJM) to coincide with presentation of the data at the European Association of Urology meeting in Stockholm, Sweden. Print version of results will be in the March 26 issue of NEJM.

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

PSA tests

There were 76,693 men in the PLCO trial. Of those, 38,343 were randomly assigned to screening with six prostate-specific antigen (PSA) tests annually and four annual digital rectal exams, an exam in which a doctor inserts a lubricated, gloved finger into the rectum and feels for anything that is not normal.

The other 38,350 men were randomly assigned to usual care, but received no recommendations for or against annual prostate cancer screening.

Of those men who were screened annually, 85 percent had PSA tests and 86 percent had digital rectal exams.

Men in the usual-care arm 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 to 52 percent of men by the last screening year; and screening with digital rectal exams ranged from 41 percent initially to 46 percent by the last screening year.

Men in the study’s screening arm were referred to their usual 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 a digital rectal exam found an abnormality.

This report includes data for all participants at seven years after they joined the trial; and for 67 percent of participants at 10 years after they joined the trial.

“The PLCO study recruited men from a population at risk for the disease,” Dr. Reding noted. “If a man has a strong family history of prostate cancer or is an African American, he should speak to his doctor about the need for prostate cancer screening.

Treatment options

Likewise, a thorough discussion of treatment options should be part of the discussion.” Other important findings of the study include:

• At seven years, 22 percent more prostate cancers were diagnosed in the screening arm. This increased frequency of prostate cancers diagnosed in the screening group remains higher even after 10 years of follow-up.

• The vast majority of men in both groups who developed prostate cancer were diagnosed with relatively early disease, and the number of later-stage cases was similar in the two groups. However, men in the usual-care group had more prostate cancers that were more aggressive. Since a smaller number of men with more aggressive prostate cancer were in the group followed more closely, it is possible this may eventually lead to a mortality difference between men in the two groups, but data analyzed so far have not shown such a difference.

• Men in both groups diagnosed with prostate cancer at the same stage received similar treatments for the disease. This reflects the PLCO study design policy of not mandating specific therapies.

• At seven years, 50 deaths were attributable to prostate cancer in the screening group and 44 deaths were attributable 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.

“NCI wants to understand why some prostate cancers are lethal, even when found early by annual screening, and what approaches can be used to identify these more aggressive cancers when they can be effectively treated,” said Christine Berg, M.D., NCI leader of the PLCO trial and senior study author.

Unnecessary treatment?

PLCO data are being made public now because the study’s Data and Safety Monitoring Board, an independent review committee, saw a continuing lack of evidence that screening reduces death due to prostate cancer and suggested that screening may cause men to be treated unnecessarily.

The Monitoring Board also supports continued follow-up of all participants so every participant is tracked for at least 13 years.

Nearly 155,000 healthy women and men between ages 55-74 joined PLCO and were assigned at random to one of two study groups.

One group received routine health care from their health providers. The other received a series of exams to screen for prostate, lung, colorectal and ovarian cancers.

Screening of participants ended in late 2006. Follow-up of participants is anticipated to continue for several more years.

Editor’s note: Besides Marshfield Clinic, other PLCO research sites include Birmingham, Alabama; Detroit, Michigan; Denver, Colorado; Honolulu, Hawaii; Minneapolis, Minnesota; Pittsburgh, Pennsylvania; Salt Lake City, Utah (with a satellite center in Boise, Idaho); St. Louis, Missouri; and Washington, D.C. For more information, go to: the National Cancer Institute's news site.