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Speaker 1: Yeah, sure. We were tasked with fighting over the clinical implications of a name change. It was me, Dan, Renu, and Brian that's in the room, and so we just came up with a list. One of them was debated a little bit, but there likely would be decreased treatment rates for what we now call grade one disease because we saw there's still what we consider reasonably high levels of treatment for pure grade one. Potentially that may go away, especially if payers step in and say, "We're not going to pay for 40 days of proton beam therapy for ASAP," or whatever you call it.

Decreased burden of diagnosis on the patient side, which I think is a big deal. Decreased being labeled a cancer patient. We talked about surveillance and how that may be altered for those of us who do a lot of active surveillance, and we all felt it would likely decrease the intensity of surveillance for some of the men.

Decrease in imaging and additional testing perhaps along those lines as we deescalate the level of surveillance for some of the men. Also, decreased imaging and decreased surveillance biopsies over time.

The risks? We discussed the risk of increased loss-to-follow-up, which we felt may be high, and missing some men. If they're now told it's not cancerous, they may not come back. They may not follow up, yet we have patients that we do tell them they have low-grade cancer now, and some of them don't even follow up. We don't know how different that would be, but likely there would be a higher risk of increased loss-to-follow-up.

We talked about how it may affect our decision to undergo biopsy, those of us who still evaluate men with elevated PSA, how that would be affected. We felt it likely wouldn't necessarily change knowing that there was this other entity out there. I mean, a lot of us practice now by upfront telling patients we may find a low-grade cancer from a biopsy, which we may not even recommend treatment for. That may not necessarily change our biopsy rate.

We talked about changes in potentially referral patterns, increasing the proportion of patients that we see with more high-grade disease needing more active treatment. This goes along the lines of decreasing the burden of low-risk disease and intensity of surveillance.

And then we also discussed, which was already brought up, would we see more grade group two being called by pathology because of this?

Speaker 2: I have a question, so I'm just curious for everyone. We talk about this upgrading. Say if we have a GG2 with less than 5% Gleason pattern four, would that be enough to pull the patient out of active surveillance?

Speaker 1: No, not necessarily. It depends.

Speaker 3: Across the country, in our country at least, any pattern for the most part is de facto treatment in a healthy person. Although, it's changing. That is changing just as it is for grade one. But I would say...

Speaker 1: Also here.

Speaker 4: I mean, at UCSF now, this is default active surveillance. But we're an outlier.

Speaker 1: Right. If you look at treatment across by grade, we already more than what... What'd you say? The current rates for grade group one are still...

Speaker 3: 50% across the board.

Speaker 1: Grade group two it's probably 90%, I bet.

Speaker 4: It's actually less than that, and there have been a couple of other studies. Michigan's down to about 75, 80% treatment for grade group two because they've really gone after surveillance on this protocol.

Speaker 5: But to his question, do you have data on the percent of four?

Speaker 4: It's like 5%.

Speaker 5: Is this just grade group two, the whole collection? Or is it...

Speaker 3: If you drill down to which grade group two are going on surveillance, it is mostly low-volume use one. But many of us have talked and blow back if this is discomforting.

But if we had to redo the Gleason system and blow it up, pattern three wouldn't be a cancer. Every report on biopsy or prostatectomy is some quantitative measurement of the amount of pattern four and five because that is what drives prognosis of management.

It couldn't be here, but just one of the other pathologists involved in CANARY has decided just to bifurcate the entire thing. He's got this grid of remapping out the entire classification. But basically draws a line and says, "These patterns matter, these patterns don't," and that's it. Either it's real cancer or it's not.

Speaker 6: One more point is even in areas where there's really high rates of surveillance for lower-risk disease, there's still a high rate of treatment after four or five, six, seven years. That's often unnecessary treatment, often driven by patient or provider anxiety because there's some subtle change in MRI.

Speaker 7: Yeah, I think this was what I was meant to be talking about, was the treatment of the group twos. I think this is a major advantage of redesignation is that it's going to be easier to get patients with low-volume pattern grade group two onto surveillance. Because you could say, "Well, you have cancer, but a very small amount of it," which is a much easier way of saying things than, "Well, you've got low intermediate risk or something like that." I think that's really, really critical.

One problem that we have right now [inaudible 00:05:39] just published this, we had a patient who had low-volume Gleason grade group two, was upgraded. Both the amount of pattern four and the amount of pattern three went down in the new biopsy, but the pattern three went down more than the pattern four. He became a grade group three, right?

At the same time, we had another patient who went from one to 10 millimeters of pattern four, but the grade group three went up even more. It went from two to 16 millimeters or whatever it was. And so that guy remains a grade group two. This is the kind of problem we're facing by calling pattern three cancer and sticking with ratios. It's making it very difficult to do active surveillance on a group of patients that we all agree could be eligible for active surveillance, i.e., a patient with pattern four, but not very much pattern four.

Speaker 3: All right, let's keep moving. We're going to be a little bit over my shoulders.