Jim Foley (left) has battled prostate cancer several times with the help of oncologist Michael Morris (right) and a clinical trial that's had him in remission more than a year.

Of the roughly 190,000 men diagnosed with prostate cancer in the United States every year, many have slow-growing tumors that are unlikely to spread. Without treatment, men with nonaggressive tumors will likely live for decades and eventually die of something unrelated. But others will have cancers that spread to lymph nodes and bones. Predicting, on initial diagnosis, which tumors are deadly is a matter of guesswork for physicians.

The blood test used to screen men for prostate cancer—called PSA because it measures the level of prostate-specific antigen—is little help in predicting how a tumor will progress. PSA levels can be just as high in men with slow-growing cancers, or no cancer at all, as in men with aggressive tumors. Because doctors tend to err on the side of caution, patients with nonaggressive tumors are often treated the same as those with more high-risk cancers. As a result, the value of the PSA test has long been debated.

“It's a major clinical challenge,” says HHMI investigator Arul Chinnaiyan, at the University of Michigan Medical School. “We end up overtreating because physicians can't tell the difference between these aggressive tumors and not-so-aggressive ones.”

With Chinnaiyan's recent discovery of a gene that drives more than half of prostate cancers, however, and work by other HHMI investigators, physicians may soon have new tools to predict the course of prostate cancer and identify the most aggressive tumors.

They're developing new treatments, too, and Foley can attest to their success: In 2008, during a recurrence of his cancer, he was one of the first patients to enroll in a clinical trial for a novel prostate cancer drug developed in part by HHMI investigator Charles Sawyers at Memorial Sloan-Kettering Cancer Center (MSKCC). Today, Foley's cancer is in remission. When he thinks “What next?” he's planning his retirement or his next trip to Virginia or Iowa to visit his daughters and grandkids, not deciding how to treat his cancer.

Foley's diagnosis came after an annual PSA test, which men are encouraged to undergo beginning at age 50. A PSA of up to 4 (measured in nanograms per milliliter) is generally considered normal. Higher levels can be okay too, though—it varies from person to person. The rate at which PSA changes is often more indicative than its level. The red flag for Foley came when his PSA rose from 4 one year to 10 the next.

In December 2008, the New England Journal of Medicine presented the case of a 63-year-old man with rising PSA scores and polled more than 3,000 doctors on how they would treat him. They were split three ways: about 39 percent said they would remove the patient's prostate; about 33 percent would treat the tumor with radiation; and about 29 percent would wait and monitor the patient's PSA levels.

With this lack of consensus, the decision often comes down to a gut reaction by an informed patient. Foley and his doctors—including oncologist Michael Morris at MSKCC, who became his primary prostate cancer doctor—weighed the options after considering his PSA levels, his age, general health, and MRI scans.

Photos: Chris Jones

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