prostate cancer discovery

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the patrick c. walsh prostate cancer research fund

Understanding Prostate Cancer Progression During Active Surveillance

Did the low-grade cancer somehow morph into high-grade disease, or did both low- and high-grade disease just happen to spring up together?

Urologist H. Ballentine Carter has done pioneering research in prostate cancer for decades, but he's never talked about it like this: Think of low-risk prostate cancer as a turtle, intermediate-risk cancer as a rabbit, and high-risk cancer as a bird, he says. "The classification depends in large part on the cancer grade. If turtles, rabbits and birds were put into a fenced area (the prostate), the turtles would never leave, or spread to other parts of the body. The rabbits would sometimes leave, and the birds would often leave."

Carter has been thinking about the different risk levels of prostate cancer particularly as it has to do with low-risk cancer – the men who qualify for the Active Surveillance program, which he began 15 years ago and continues to lead. With funding from the Patrick C. Walsh Prostate Cancer Research Fund, Carter has teamed up with some impressive Hopkins co-investigators — geneticist William Isaacs, pathologists Angelo De Marzo, Srinivasan Yegnasubramanian, Jonathan Epstein and Michael Haffner, and mathematical analyst and scientist Sarah Wheelan. "The purpose of this project is to determine whether turtles can evolve into rabbits and birds," says Carter. The scientists have identified men in the Active Surveillance program who were initially diagnosed with low-grade disease, but during the close follow-up turned out to have high-grade cancer found on a repeat biopsy, which resulted in radical prostatectomy. Using those pathology specimens, "the low-grade 2016and high-grade components of the cancer within the same prostate will be genetically sequenced to determine how these cancer cells are related," says Carter. The scientists hope that by making a "genetic fingerprint" of these tumors, they can answer some key questions, including: Did the low-grade cancer somehow morph into high-grade disease, or did both low- and high-grade disease just happen to spring up together? Do these high-grade cancers leave some sort of calling card — a genetic marker that could be used to predict whether men have cancers that are actually birds in turtle clothing? The investigators will also look at a control group — low-grade cancer that has remained low-grade, "to determine if there are high-grade markers within these low-grade cancers," Carter continues. "Lastly, if we find definitive markers of high-grade cancer within low-grade cancer, we will sequence prostate biopsies to determine if disease that we diagnosed as low-grade actually contained high-grade markers. This information could help men with a diagnosis of low-grade cancer know whether they will eventually need treatment."

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