Annual screenings for prostate cancer 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. The University of Pittsburgh Cancer Institute (UPCI) is one of 10 sites that enrolled participants into the PLCO, which was designed to assess the effectiveness of prostate cancer screening.

"Prostate cancer screening in the trial increased detection of early prostate cancer," said Joel L. Weissfeld, M.D., M.P.H., principal investigator for the UPCI PLCO Cancer Screening Center. "However, over the first seven to 10 years of follow-up, we have not yet seen a corresponding decrease in deaths from prostate cancer."

Results appear online March 18 in the New England Journal of Medicine, coinciding 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 journal's March 26 issue.

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 of prostate cancer screening in men younger than 75 and recommended against prostate cancer screening in men ages 75 and older.

Of the 76,693 men in the PLCO trial, 38,343 were randomly assigned to screening with annual prostate-specific antigen (PSA) tests for six rounds and digital rectal exams (DRE) for four rounds. A DRE is an exam whereby a doctor inserts a lubricated, gloved finger into the rectum and feels for abnormalities. 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 DREs. 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. Men who were screened annually 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 DRE 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. Other important findings include:

- At seven years, 22 percent more prostate cancers were diagnosed in the group that participated in annual screenings (2,820 men vs. 2,322 in the usual-care group). This same pattern also was observed among those followed for up to 10 years (with 17 percent more prostate cancers diagnosed for those screened annually).

- The vast majority of men in both groups who developed prostate cancer were diagnosed with relatively early stage disease, and the number of later-stage cases was similar in the two groups. However, using the Gleason scoring system, which assesses tumor aggressiveness, men in the usual-care group had more prostate cancers that fell into the Gleason 8 to10 range, which marks them as more aggressive. The smaller number of men with prostate cancer with a Gleason score of 8 to10 in the intervention group 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 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 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.

"The National Cancer Institute 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 author of the study.

Another report in this same online publication of the NEJM is from the large European Randomized Study of Screening for 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 also were screened, on average, every four years as opposed to annually in the PLCO.

"These long-awaited results from PLCO and ERSPC add new information to ongoing discussions about best prostate cancer screening policy and practices," said Dr. Weissfeld.

The PLCO data are being made public now because the study's Data and Safety Monitoring Board (DSMB), 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 the suggestion that screening may cause men to be treated unnecessarily. The DSMB also supports continued follow-up to track participants for at least 13 years.

The PLCO is a large-scale clinical trial, sponsored and run by NCI's Division of Cancer Prevention, begun in 1992 to determine whether certain cancer 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.

Nearly 155,000 women and men between the ages of 55 and 74 have joined the PLCO trial. At entry, participants were assigned at random to one of two study groups: One 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.

Founded in 1984, the University of Pittsburgh Cancer Institute became an NCI -designated Comprehensive Cancer Center in 1990. UPCI, the only cancer center in western Pennsylvania with this elite designation, serves the region's population of more than 6 million. Presently, UPCI receives a total of $154 million in research grants and is ranked 10th in funding from the NCI.

University of Pittsburgh Cancer Institute

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