prostate cancer discovery


New Test May Help Avoid Repeat Biopsies


prostate cancer detection
Partin and Epstein: Test predicts whether cancer may have been missed on the biopsy.

If the biopsy needles can’t
always find cancer, is it
possible that the presence of
these other somewhat weird,
hypermethylated cells might act
as the proverbial canary in the
coal mine? A new test suggests
that the answer is yes.


Nearly one million American men undergo a prostate biopsy every year. Three out of four of these men will be told that they don’ t have cancer because when pathologists looked at their tissue cores under the microscope, they didn’t see anything suspicious. However, of these 750,000 negative biopsies, an estimated one-fourth — nearly 190,000 mean — actually do have prostate cancer; the biopsy needles just missed it.


Many of these men will have to go through at least one repeat biopsy, maybe more, before their cancer is diagnosed.


For more than 20 years, ever since regular screening for prostate cancer began to be widespread, doctors have looked for a way to avoid unnecessary repeat biopsies. At the same time, Brady scientists led by William Nelson have been studying the nature of prostate cancer cells, and of the cells per colating alongside the cancer. They noticed that many of these cells showed methylation changes — “epigenetic” changes to the biochemical composition of their DNA that make the cells act differently. If the biopsy needles can’ t always find cancer, is it possible that the presence of these other somewhat weird, hypermethylated cells might act as the proverbial canary in the coal mine? A new test, a tissue assay called Confirm MDx, suggests that the answer is yes. “This assay looks at the methylation, the alteration of the DNA, of three genes,” says Alan W. Partin, M.D., Ph.D., the David Hall McConnell Professor and Director of the Brady, “and predicts whether cancer may have been missed and that a repeat biopsy should be recommended.”


Recently, Partin and pathologist Jonathan Epstein, M.D., led a multicenter study of 350 men who had under gone PSA tests and who had high-risk variables (such as high-grade PIN and a high PSA), but who had a negative prostate biopsy. The men were patients at five major urologic centers, including Hopkins; the study was called DOCUMENT, for Detection of Cancer Using Methylated Events in Negative Tissue. The tissue methylation assay was used to analyze the DNA from 3,687 negative tissue cores for epigenetic abnormalities, and the results were compared to findings on a repeat biopsy done within two years. Epstein, the Reinhard Professor of Urologic Pathology and Director of Surgical Pathology, reviewed all of the biopsy tissues . The assay performed like a champ, accurately ruling out the presence of cancer up to 88 per cent of the time. The study’s results were published in the Journal of Urology. “This study shows that by looking for the presence or absence of cancer in a different way, we may be able to offer man y men peace of mind without putting them through the pain, bleeding, and risk of infection that can come with a repeat biopsy,” says Epstein. “With prostate biopsies, there is often very little cancer, which makes it difficult to perform molecular prognostic and predictive tests. The DOCUMENT study overcomes this problem, because it looks at benign tissue, not just the cancer. There is a lot of benign tissue , which is why we think it performs so w ell. “Overall, if there is an absence of methylation in all three biomarkers, there is an 88 per cent likelihood you don’t have cancer,” Epstein says. “The test isn’t 100 percent perfect, but it is a major step forward.”

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