Ra-223: New Arrow in Prostate Cancer Quiver

Howard I. Scher, MD; Johann S. de Bono, MD


June 10, 2013

In This Article

Imaging as a Biomarker

Dr. Scher: The lesson is that we have to treat imaging as a biomarker, which we will talk about in more detail, and we can't use the same assessment tools to determine whether a drug is working as a function of the mechanism of action.

Dr. de Bono: You are absolutely right. One of my big concerns is that patients are so dependent on PSA monitoring, which is essentially a pharmacodynamic biomarker of androgen receptor signaling, that decisions are being made incorrectly on the basis of PSA. We will be developing drugs that will not affect PSA but that will benefit patients.

Dr. Scher: We already have.

Dr. de Bono: Ra-223 being one of them and cabozantinib being another. We have to educate our patients, our clinical colleagues, and our urologists to rethink what PSA and bone scans mean. Essentially, with bone scans, we are measuring osteoblast uptake of technetium-99m. The study presented today on sodium fluoride PET[8] was not that different. What did you think about that study?

Dr. Scher: To me it's another biomarker. Essentially, every time we bring in a new test, whether it's a laboratory test or clinical parameter, we essentially have to start over and try to understand first how to measure it. If you take the same patient and do a technetium bone scan and then do a sodium fluoride PET, it looks like 2 different people. Many nuclear medicine physicians are not familiar with how to interpret changes in the sodium fluoride. We don't know what those changes actually mean. If we are going to test it as a biomarker, there has to first be some consistency in how the test performs, just from an interpretation point of view, ignoring how you acquire the images. So, Evan Yu[8] from the University of Washington and Mike Morris[9] from Sloan-Kettering are looking at what happens when you do 2 sodium fluoride PET scans a week apart -- are they the same?

Dr. de Bono: The variability.

Dr. Scher: If you test and retest, are the interpretations consistent? That is the type of foundational information you need to go forward.

Dr. de Bono: It's key. We have to have a very clear road map for developing biomarkers of any sort for the prostate cancer community and be very rigorous in looking at reproducibility, variability, and what changes mean with respect to patient care.

Dr. Scher: Right. There is a road map that essentially says, "First be able to measure it." If you think about how Ra-223 will be tested going forward, many would consider simply adding docetaxel. In fact, Michael Morris has led a trial showing that this can be given safely on a repetitive basis. If you look at the history of docetaxel combinations in prostate cancer, they have not been successful. That is a gross understatement.


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