Alicia Morgans: Hi. I'm so delighted to be at APCCC 2022, where I'm here with Dr. Rob Reiter, who is the Chair of Urologic Oncology and a Professor of Urology at UCLA. Thank you so much for being here.

Rob Reiter: Good to be here.

Alicia Morgans: Wonderful. So I wanted to talk with you a little bit about the use of MRI and active surveillance, which I think is such an area of interest in the field. And certainly, there's a lot of interest in active surveillance by patients and providers alike. So tell us a little bit about this, maybe active surveillance and its importance, and then specifically how MRI might play a role.

Rob Reiter: Sure. So active surveillance is obviously very important, because we know historically that we overtreated prostate cancer. That's what led to the downgrade in PSA as a marker. But I think that over the last 10 years, 15 years, we started to do much better. We recognize more and more patients who clearly do not need to be treated and can be safely placed on active surveillance. And the long-term data for active surveillance is very strong.

But there remain areas where there's tremendous controversy, for instance, patients who have grade two cancer, which of those patients could go on active surveillance, which might not. And so MRI has entered into the picture in terms of trying to improve our ability to properly select patients for active surveillance.

Alicia Morgans: Absolutely. And I think one of the more interesting things about MRI is that, certainly, it's increasingly used just even in our staging of localized prostate cancer. But one of the concerns, of course, is that MRI may or may not actually be able to replace a biopsy. There's a lot of talk around that. And I wonder what your thoughts are. Do you use MRI to really guide the need for biopsy, or are you thinking about replacing biopsy with MRI?

Rob Reiter: So I was a very early adopter of MRI. It's almost 20 years ago now. And we, together with one of my partners Dr. Leonard Marks, we really started a pretty active MRI guided biopsy program almost 14 years ago. So we are in the habit of doing MRIs prior to biopsy, but we still do do biopsy, because even grade five MRI targets are not always cancer. And of course, we need the pathologic or histologic information to make management decisions. Is there cribriform? Is there intraductal? How much pattern 4 is there? And you can't get that just from an MRI, although an MRI provides a lot of information that can help risk stratify and guide one's thinking.

Alicia Morgans: Absolutely. Well, and just to pick up on one of your comments with cribriform, we heard a really interesting talk by Dr. Declan Murphy, who was explaining some of the histologic patterns that we might see and how patients who have a Gleason 7 cancer who do have cribriform are probably not the patients you want to take a chance on in terms of active surveillance.

Rob Reiter: Right.

Alicia Morgans: What are your thoughts there?

Rob Reiter: So A, I agree. B, it's kind of cool because we published a paper a few years ago. Initially, there was a couple of papers suggesting that cribriform cancers were very poorly visualized by MRI, but we actually showed the opposite. Not only that, but we sequenced tumors that were highly visible in MRI versus those that were actually not visible, that looked histologically the same, Gleason 7. And we found that visualized tumors were associated with genes that are classically associated with cribriform, and cribriform cancers were increased in the group that had MRI grade five targets.

So in fact, MRI does provide just biological information in addition to where's the lesion that you need to biopsy, and cribriform and intraductal cancers are more likely to present as pattern five or PI-RAD 5 on an MRI.

Alicia Morgans: And that's so interesting. And thank you for bringing that up. I think that it's data like that pushes some individuals to think, "Well, we don't necessarily need to have biopsies so often. Maybe we can just use the MRI." And I know you spoke to the need to have the histology and to have that confirmation. Is there an opportunity to decrease the number of biopsies over time, or where might we spare patients a little bit of trouble?

Rob Reiter: So I think the MRI data is increasingly clear that if you have an elevated PSA, but you have a negative MRI that the likelihood of having significant cancers is significantly lower, and so that you can avoid biopsy in a substantial number of patients. Still, there are some patients who, despite a negative MRI, need a biopsy. But you can use things like biomarkers, PSA density to really select the patients who would still need a biopsy.

If you have a PSA density greater than 0.15, the literature shows you have about a 20% risk of having a significant cancer despite a negative MRI. But if it's lower, you only have an 8% risk. So there's no doubt that MRI is decreasing the total number of biopsies that are done in patients.

Alicia Morgans: So important. So the final question I want to ask is, for those who are still trying to get their active surveillance programs up and running or to feel more confident about their approach in integrating MRI, how often are you repeating the MRI in your active surveillance cohort?

Rob Reiter: So I'd say a couple things about the use of MRI and active surveillance. So we just published a paper. Adam Canera, former postdoc with us, just published a really good paper in European Urology, showing that if you have any cancer in an MRI target, you are more likely to basically fail active surveillance. So we recommend a confirmatory biopsy, usually six to 12 months after an initial biopsy. And if the target has cancer in it, you have to watch those patients more closely. Even if the target's grade one, and if they have a grade two cancer, they have about a 40% chance or threefold risk of actually failing active surveillance over time.

So based on that, our recommendation, and it's variable, there's no hard facts on how often to do these, we usually do it every year, an MRI, inpatients where we know there's a substantial risk of progression. Whereas if they have grade one cancer, they have a negative MRI, perhaps you need to do MRIs and biopsies much less often, because MRI is a very strong negative predictor of significant cancer. But if you have a positive MRI, then those are the patients you probably need to follow more closely.

And then the other point I would just say is that monitoring MRI changes, that can work, but many patients will have progression with no change in the MRI. So the MRI, there will be a lesion that's a centimeter. It remains a centimeter. So you still have to biopsy them. You can't just follow the MRI and not biopsy because there's no change.

Alicia Morgans: Well, thank you for that. And I just want to emphasize that point, that there can be change in histology even when you don't have a change on the MRI.

Rob Reiter: Correct.

Alicia Morgans: So really important to keep that in mind. Well, thank you so much for sharing your expertise and for-

Rob Reiter: You're welcome.

Alicia Morgans: ... taking the time to talk today.

Rob Reiter: Anytime. Good to see you.