New blood test may someday help guide the best treatment for aggressive prostate cancer

Charlie Schmidt

Editor, Harvard Medical School Annual Report on Prostate Diseases

Tumors that spread, or metastasize, in the body shed cells into blood that doctors can scrutinize for insights into what a patient’s cancer might do. Analyzing these so-called circulating tumor cells (CTCs) isn’t part of routine care yet, in part because they’re so hard to pick out of the millions of normal cells in a blood sample. Still, scientists are making progress in this area. And in June, a research team reported that treatment decisions made on the basis of CTC testing had increased lifespans in men with an aggressive type of metastatic prostate cancer.

Doctors usually treat metastatic prostate cancer with drugs that interfere with how a man’s body makes or uses testosterone, which is the male hormone (or androgen) that accelerates the tumor’s spread. If the standard hormone-blocking treatments aren’t effective, then doctors have two other options: they can either give chemotherapy drugs known as taxanes, or shift to other hormone blockers that act specifically on the cancer cell’s androgen receptor. Known as androgen receptor signaling (ARS) inhibitors, these alternative hormone blockers include an agent called enzalutamide and another called abiraterone. But neither of them will work if the androgen receptor has a genetic mutation called AR-V7 that also makes the tumors grow very aggressively.

With mounting evidence showing that the mutation doesn’t affect a man’s response to taxanes, researchers began to wonder if screening for AR-V7 in CTCs could guide them to the most appropriate treatment. That’s what a team at the Memorial Sloan Kettering Cancer Center in New York set out to investigate.

Here’s what they did

They began by collecting blood samples from 142 men with metastatic prostate cancer who weren’t responding to standard hormonal therapy. After their CTCs were screened for the AR-V7 protein, the men were treated either with ARS inhibitors or taxanes at their doctor’s discretion. The treating doctors had no knowledge of each patient’s AR-V7 status.

Half the men wound up being treated with ARS inhibitors and the other half with taxanes. And as it turns out, the men who tested negative for AR-V7 lived longer when treated with ARS inhibitors; their median survival was 19.8 months, compared to 12.8 months among the taxane-treated men. Conversely, the men who tested positive for AR-V7 lived longer when given taxanes: their median survival was 14.3 months, compared to 7.3 months among the men treated with ARS inhibitors.

The results mark a significant advance for AR-V7 as a guide to more effective, personalized treatment, and also for CTCs as “liquid biopsies” that doctors can easily sample for important prognostic information.

“The research adds to an expanding body of knowledge related to AR-V7 in prostate cancer,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. “Hopefully the utility and availability of this test will become more widespread, and further enhance our ability to select the best treatments for specific patients based on the molecular characteristics of their disease.”

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