The initial results also confirm that the design of the massive study, which will continue until 2019, will indeed allow researchers to determine whether current screening practices reduce death from prostate cancer, according to the authors. They present their analyses in two papers, one in the March 16 issue of the Journal of the National Cancer Institute and the other in the March issue of the Journal of Urology.
The study is part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial being conducted by researchers at Washington University School of Medicine in St. Louis and several other institutions.
Uncertainty about the need for prostate cancer screens stems from several factors. PSA and DRE tests can be inaccurate, giving both false negatives and false positives. In addition, neither test indicates how aggressive a man's cancer is. Furthermore, because prostate cancers grow slowly in many cases and treatments can have unpleasant side effects, treating the cancer may be less desirable than leaving it alone, especially in older men.
"But the main thing is we don't know whether screening saves lives," says Gerald L. Andriole Jr., M.D., head of the Division of Urologic Surgery at Washington University and Barnes-Jewish Hospital. "Our study follows about 75,000 men, half of whom we are screening, and half of whom are getting conventional care. By comparing groups over the long term, we will see what difference screening makes in survival rates."
Begun in 1993, the PLCO study has screened 34,244 men across the United States, aged 55 to 74, for prostate cancer and followed their subsequent medical history. The PLCO protocol advises men to consult their own physician if either the PSA or DRE tests given by PLCO are suggestive of cancerous growth.
The outcome of the study should aid patients and doctors in making decisions about diagnosis and treatment of prostate cancer. "It's a complex decision," Andriole explains. "Say your father had an abnormal PSA test, and he's 76 and has a bad heart, diabetes, or recently had a stroke. Frankly, the patient and doctor have to base their decision on the probability that one of those factors may cause death before prostate cancer."
Of the men screened by PLCO, about 14 percent had positive screening results, indicative of possible cancer. Approximately 8 percent screened positive by PSA test, and about 7 percent screened positive by DRE test. Only about 1 percent of these results overlapped, demonstrating the importance of using both screening methods.
"We were hopeful some years ago that men could just have the PSA blood test, because men hate the rectal exam," Andriole says. "We've found that if you omit the DRE, you'll miss a certain percentage of cancers."
Three-fourths of the men with positive PLCO screens went in for further diagnostic evaluation with their personal physician. The physicians would decide whether to conduct their own screenings and whether to subsequently perform a biopsy, which is needed to confirm the presence of cancer before treatment.
About a third of men with abnormal tests had a prostatic biopsy within a year of the initial screen. Of men with PSA readings higher than normal, 64 percent underwent biopsy within three years. The higher the PSA readings, the higher the biopsy rates. The biopsy rate in men with positive DRE alone was 28 percent.
The initial data indicate that younger men, men with a family history of prostate cancer and African American men are more likely to have a biopsy after an abnormal screening result. "These statistics parallel many medical recommendations and reassure us that good judgment is being applied to the evaluation of the initial screen," Andriole says. "We are confident that when the study is ultimately completed, it will truly measure the effect of current medical practices."
In men with suspicious PSA readings, regardless of DRE findings, biopsy revealed cancer almost half the time, while in men with suspicious DRE tests, regardless of PSA levels, biopsy found cancer about a third of the time.
The majority of men with cancer had localized cancers. About ten percent had more serious advanced forms. These advanced cancers were linked to higher PSA numbers and suspicious DRE results.
Overall, 1.4 percent of the approximately 34,000 men screened were subsequently diagnosed with prostate cancer by tissue biopsy. This rate of detection is lower than in two previous studies of prostate cancer screening, which found cancer in 4.2 and 3.2 percent of patients, respectively.
This lower rate of detection more accurately reflects the contemporary standards of practice, because biopsy and diagnosis took place outside of the PLCO study, according to the authors.
Andriole GL, Levin DL, Crawford ED, Gelmann EP, Pinksy PF, Chia D, Kramer BS, Reding D, Church TR, Grubb RL, Izmirlian G, Ragard LR, Clapp JD, Prorok PC, Gohagan JK. Prostate cancer screening in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial: Findings from the initial screening round of a randomized trial. Journal of the National Cancer Institute, Mar. 16, 2005.
Pinsky PF, Andriole GL, Kramer BS, Hayes RB, Prorok PC, Gohagan JK. Prostate biopsy following a positive screen in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The Journal of Urology. March 2005;173:746-751.
Funding from the National Cancer Institute supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.