What to Do If PSA Comes Back After Surgery? New Test May Help                              


The numbers are troubling: About 240,000 men in the U.S. are diagnosed with prostate cancer each year. Of those, about half – 120,000 – will undergo radical prostatectomy, and of those, about a third, 40,000 men, will eventually have a return of PSA , or a "biochemical recurrence" of cancer. "These men present a management dilemma to many clinicians," says urologist Ashley Ross, M.D., Ph.D. "In fact, there are no standardized management plans for these men, and this is primarily because their experiences are so varied." Some men with a rising PSA after radical prostatectomy eventually develop metastatic cancer; in others, cancer returns at the local site and can be treated successfully with radiation. And for some men, the only sign that at least a few prostate cancer cells still exist is the fact that PSA shows up in a blood test. "Even among men who experience metastasis after a biochemical recurrence, the time to metastasis can vary over an order of magnitude."

Using a newly developed clinical test based on the specific pattern of gene expression from the primary tumor, Ross, with urologist Edward Schaeffer, M.D., Ph.D., and colleagues from GenomeDX and the Mayo Clinic found that they could help predict which men with an elevated PSA after radical prostatectomy will go on to develop metastatic disease. Although further studies are required to confirm their findings, "these results suggest that this molecular test can be used to better identify men who will need more intense, or earlier treatment at the time of their PSA recurrence, and which men will not need additional treatment and can be spared having to go through it."

"Some of these men live for many
years and do not die of their
cancer, while others experience
early metastasis."

Men at Very High Risk

In other news, Ross, Schaeffer, and urology resident Debasish Sundi, M.D., have defined a new subgroup of men with localized prostate cancer: men at very high risk. "When you look at what the National Comprehensive Cancer Network (NCCN) defines as high-risk prostate cancer," says Ross, "you can see that some of these men live for many years and do not die of their cancer, while others experience early metastasis even after aggressive local treatments." Ross, Schaeffer and Sundi believe this category is too broad. To help define it, and to offer more specific guidance for men with high-risk disease, they searched the Johns Hopkins radical prostatectomy database and identified more than 750 men who fit the NCCN standard of having highrisk localized prostate cancer: These men had a Gleason score between 8 and 10; a PSA greater than 20 ng/ml; or a clinical stage of T3 or higher. "We found that 15 percent of these men could be defined as being of very high risk," says Ross. Men in this subgroup had a primary Gleason pattern 5 found at biopsy (note: this is not the Gleason sum, which is obtained by adding the most common and second-most common cancer cell patterns); or five or more cores of cancer found at biopsy with a Gleason sum of 8 to 10; or multiple NCCN high-risk features (listed above). "These men had a risk that was three times greater, when compared to other high-risk men, of having metastasis and death from prostate cancer after prostatectomy. We hope that when these very high-risk men are identified, their doctors can counsel them on getting the best treatment possible," which may include surgery, radiation, and cancer-fighting drugs or hormonal therapy, and also participation in clinical trials.

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