Fifty percent of men in the United States undergo regular screening for prostate cancer, using a test that measures levels of prostate-specific antigen (PSA), a protein secreted by the prostate gland. However, recent research looking at PSA levels after a prostate biopsy has revealed that PSA level is not a very accurate predictor of prostate-cancer risk. Prostate cancer can occur when PSA levels are what many consider to be normal. Other variables, such as family history, age, race and digital-rectal examination (DRE) results also play a role in assessing prostate-cancer risk.
Now, researchers in the Public Health Sciences Division and colleagues have developed a model to predict prostate-cancer risk in men who undergo a prostate biopsy. The details of the risk calculator appear in the April 18 issue of the Journal of the National Cancer Institute.
Prostate Cancer Prevention Trial
The data for the analysis came from the landmark Prostate Cancer Prevention Trial (PCPT), which was designed to test the effectiveness of the drug finasteride in preventing prostate cancer. The primary results of the PCPT, published in 2003, showed a near 25 percent reduction in prostate cancer due to finasteride.
The PCPT study involved 18,882 healthy men at 219 clinical sites nationwide. More than 750 men participated from the state of Washington. Participants were followed for seven years, receiving regular PSA screening and DREs annually. If tests were abnormal, men underwent a prostate biopsy to check for prostate cancer. Men also underwent biopsies at the end of the study if they had not been previously diagnosed with prostate cancer. The researchers used various statistical tests to analyze biopsy results, family history of prostate cancer, race, age, rectal-examination results and previous biopsy history.
Lead author Dr. Ian Thompson of the University of Texas Health Sciences Center and co-authors, including Chen Chi, statistical research associate, and Phyllis Goodman, biostatistician, both in the Public Health Sciences Division, used the equations generated by their analysis to develop a risk calculator that can be used to assess an individual's risk of prostate cancer. The tool is available online and can be used to calculate risk of prostate cancer and high-grade disease for men 55 years and older who have no previous history of prostate cancer and who have had recent PSA screening and DRE tests. The Web-based calculator was implemented by Peter Lin, systems analyst programmer with the Early Detection Research Network
"This risk-calculator model uses variables that go beyond only PSA levels to help patients and physicians decide whether a prostate biopsy should be performed," the authors wrote. "We anticipate that the area of cancer-risk modeling — including the incorporation of new risk variables and the understanding of patient decision making — will have a measurable clinical impact over the next few years."
A tool for testing decisions
In an accompanying editorial, Dr. H. Ballentine Carter, Johns Hopkins School of Medicine in Baltimore, brings up concerns about overtreatment of prostate cancer if the model were to pick up the nonlethal varieties of prostate cancer. "In the absence of accurate markers of life-threatening disease, I do not believe that physicians should endorse any approach to predicting the risk of prostate cancer that is likely to increase the diagnosis of biologically unimportant cancers," Carter said. "Once we have the ability to assess multiple risk factors (e.g., PSA or other new markers) in populations for which the long-term outcomes are known, such approaches will help identify those men who will benefit from active treatment."
Goodman said, "A man with a PSA test result goes to his physician with a group of other risk factors for cancer including his family history of prostate cancer, his ethnicity, his age and his prostate-examination findings. Also, he may have had a previous prostate biopsy. In the past, his physician, recognizing all of these items as risk factors for the disease, had to integrate them in his head — a process that was often overlooked. Now, we have a powerful tool that helps both the physician and patient incorporate these risk factors, assess his own personal risk and come to a personalized decision as to whether further testing is necessary."
Funded by the National Cancer Institute, the PCPT trial was coordinated by the Hutchinson Center's Southwest Oncology Group. PHS houses the SWOG Statistical Center, which oversaw every aspect of the trial, from study design and effective data management to final statistical analysis.