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Matt Cooperberg: Well, I'm just going to really, honestly, just echo a few other things Scott has already said. First of all, again, this term cancer resonates in the world and has done for thousands of years, and the nomenclature really does matter as we see when we look at how men react to the diagnosis. The fact of the matter is what we call cancer histologically is basically a normal feature of male aging. If you live long enough, every man is going to have a few glands of what we call Grade Group 1 cancer. And we're trying really, really hard not to find it, okay? We've really changed our diagnostic paradigm in the last five years. We've got more biomarkers than we know what to do with, we've got MRI, we use these tests to separate men between Grade Group 2 and higher and benign type Grade Group 1. So all these tests are explicitly intended to not find the Grade Group 1s. And it's working.

In CaPSURE, old times, 50% of the cancer seems to be low grade. Now in the AQUA figure we're down to 20% of the UK where you don't get a biopsy without an MR. So Grade Group 1 diagnosis is basically an accident, at this point, of the pursuit of finding Grade Group 2, so if you find it accidentally, we really should not be considering it cancer.

As Scott just mentioned, we're making a lot of progress with surveillance, we're up to 60% from 30% in the last six years, but there's still extreme variability. This is the likelihood of getting surveillance with low-risk disease by individual urologists, which ranges from 0% to 100% depending on whose door you knock on. This is still a major problem, and a lot of this is driven by the fact that either the physicians or patients react to the cancer diagnosis.

And this is not really cancer the way we think about cancer in the modern sense. It does not have the hallmarks of malignancy when we think about what really makes a cancer, either from the framework of a patient vantage point or from the framework of molecular biology beyond the histology. So this may look like cancer histologically, but if it doesn't act like one, can we really call it a duck? It looks like one, but it's neither quacking, walking, nor flying.

At the end of the day, there is this concern that Grade Group 1 has some molecular changes consistent with what we might find in Grade Group 2. The same is true of normal. We've drawn a line for a long time, somewhat arbitrarily, between ASAP and Grade Group 1 based on size. There's no particular reason that that's where the line has to arbitrarily be drawn when we use the word cancer. It could just as easily be between Grade Group 1 and 2.

At the end of the day, a lot of us think that surveillance would look exactly like it does now. We wouldn't manage men any differently. Would a small number of men disappear from followup because they don't have the diagnosis? Yeah, probably. But at the end of the day, if we convince the primary care world who are really responsible for finding these cancers when they are curable, finding the high-grade cancers when they're curable through screening, if we convince the primary care world that overdiagnosis is over and we get a B recommendation or at least a C change in practice and we screen men at younger ages, we will have a public health impact that far, far outweighs anything we're worried about in terms of loss to followup.

With that, I'm going to pass it on to Dr. Kibel who's going to give a counter viewpoint.