Planting the Seeds of Prevention - Siteman Cancer Center

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Gerald Andriole, MD, talks with longtime patient Paul Colombo of St. Louis. In 1990, a then-new PSA test detected Colombo’s prostate cancer. Andriole performed surgery and still provides follow-up care. 10 The Alvin J. Siteman Cancer Center Unearthing Disease Refining the Science of Prostate Cancer Screening It is evidence of the complexity of prostate cancer that so much of the disease’s story remains unresolved, even though it is the most common nonskin cancer in men, affecting one in six, with an estimated 186,000 new diagnoses in 2008. Large studies performed over several years have examined prostate screening’s effectiveness, but still, the endings to many of its subplots have yet to be written. A major character in the prostate cancer story always has been the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, a leader in the field. It was here, beginning in 1989, that the then-new PSA test for prostate cancer — a blood test for an elevated level of the protein called prostate-specific antigen, or PSA — was systematically evaluated. In this study, more than 30,000 St. Louis-area men had their PSA levels tested regularly. If their level was abnormal, they underwent biopsies to see if they had cancer. The results were clear: The PSA test found prostate cancer when it was still contained in the small gland in 95 percent to 98 percent of the cases. “That was a terrific improvement,” says Gerald Andriole, MD, professor and chief of urologic surgery at Washington University School
of Medicine. Before the advent of the test, about one-third of men diagnosed with prostate cancer had disease that had metastasized to the bones, and another third had tumors that had grown outside the prostate. In that sense, screening for prostate cancer is an undeniable success story. But even after fine-tuning the test and beginning to examine the rate of increase in PSA rather than just the amount in the blood, there still are uncertainties. How often to test remains a question. Annual testing has been recommended, but some men with very low PSA levels may require testing only once every two to five years. Another issue is the test’s tendency to produce false-negative results. Andriole says about 15 percent to 20 percent of men with prostate cancer have a low or normal PSA level, so the blood test misses their disease. PSA also may be falsely positive. “If a man’s PSA level is 5 — a high number — he still has only about a 20 percent to 25 percent chance of having cancer,” Andriole says. In other words, up to 80 percent of the biopsies that follow a high reading find no tumor. Eliminating these false positives is highly desirable because the biopsy process is unpleasant and the costs of unnecessary care are high. To achieve greater precision, new tests are being evaluated. The PCA3 gene test looks for cancer-specific RNA molecules in cells washed out in urine, while the ProCAM test, which is being investigated by Andriole’s team, looks for DNA methylation modifications in these same cells. Not as far along in development is a test for EPCA-2, a protein expressed principally by cancerous tissue. That’s unlike PSA, a normal product of the prostate. The emerging technologies of proteomics — the study of proteins and their patterns within cells — also hold promise. Andriole says that precise patterns of many blood proteins may be closely associated with various cancers. “If we can train computers to recognize telltale patterns, we might not even need to know what all of the involved proteins do,” he says. Does screening save lives? That’s one of the biggest remaining questions, Andriole says. “The average 50-year-old man has a 3 percent chance of dying of prostate cancer,” he explains. “Altogether, when we screen a man every year with PSA, after only a few years, his chance of being diagnosed with cancer exceeds his lifetime risk of dying of it. We find five to seven times as many men with cancer as will die of it. So if we treat everyone with the disease, we’re clearly overtreating.” Overtreating is expensive, with side effects that can include incontinence and impotence. As chairman of the prostate committee of the National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Andriole seeks answers about whether screening extends life. PLCO compares men who are screened with men who receive conventional care. The prostate portion of the trial has enrolled 75,000 participants at 10 centers nationally, including Washington University School of Medicine. Objective: Perfect prostate cancer screening www.siteman.wustl.edu 11
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