Phillip Koo: Hello, my name is Phillip Koo, and welcome to the Imaging Center of Excellence at UroToday. We're very pleased to have with us today, Dr. Sigrid Carlsson, who's the Director of Clinical Research at the Josie Robertson Surgery Center at Memorial Sloan Kettering Cancer Center. Welcome, thank you for joining us.

Sigrid Carlsson: Thank you so much.

Phillip Koo: At this upcoming AdMe Tech meeting occurring in September 2022, you're moderating session called Smart Screening in Prostate Cancer. Before we dive too deep into this idea of smart screening, can you give us a quick background on what are the challenges with screening today that require us to be smarter about screening?

Sigrid Carlsson: Yeah, certainly. It's an excellent question, Dr. Koo, because I guess it depends on how you define smart. I think there are a lot of roads that can lead to Rome and I think there are a lot of people around the world that have claimed to have found this solution or the way to Rome. I think maybe the answer is there are many ways to Rome. In this exciting session and at the upcoming conference, we have investigators and PIs from all over the world who are presenting some of their ongoing work on how to solve this equation and how to keep the benefits of screening and really reducing the harms. Because, as you know, we, PSA testing is great. We know that, that can reduce prostate cancer mortality, but there's, of course, the downsides, with primarily the risk of overdiagnosis, and that's what we really want to solve that equation and that's why we call it smart screening.

And so in this session, I think we have a really interesting smorgasbord of potential solutions, and that can involve incorporating PSA plus MRI before biopsy, plus/minus biomarkers, and the sequence they're off. So it's really interesting, because there are so many different proposals. A lot of this work is now being conducted in this large scale randomized trials and ongoing effort. So I think in the next few years, we'll have the answer to how to do this. What is the solution. But as of now, we are still trying to figure this out in the research community, which is a really exciting time.

Phillip Koo: Great. If we take a deeper dive with regards to imaging, the role imaging could play in smarter screening, what are your thoughts? Where are the opportunities there?

Sigrid Carlsson: Yeah. MRI, multiparametric MRI, or sometimes biparametric, has really become the new kid on the block in the past few years in early detection of prostate cancer, to be used before proceeding to biopsy and help biopsy decisions. There are some studies and some ongoing trials, Dr. Caroline Moore will present one of those at upcoming conference, proposing to use MRI as a screening tool. So abandoning the blood test PSA, but just going straight to MRI, so a mammogram, or just like we do with women, mammography. That will be interesting, to hear the results from that study and how many MRIs you need to do in order to find one cancer.

But several of the other ongoing studies, for example, the Stockholm trial, Göteborg-2 trial, and other trials ongoing, proposed to use MRI as part of the diagnostic change. So you start with a good old PSA test, with or without any other ancillary tests, could be other biomarkers, and then you have a subset of those men who then go on to pre-biopsy MRI, because the MRI can really help you do a better prostate biopsy. The idea there is to solve this equation. So you keep the benefits, you can still detect the high-grade tumors, but you can reduce the number of men who need to undergo unnecessary biopsy and also reduce overdiagnosis. So it's like trifecta, if you will. You have better outcomes on all those things. That's what these ongoing trials are trying to solve, this equation.

Phillip Koo: Great. I've also heard a little bit of talk and excitement about ultrasound, microultrasound. Do you think that has a role, moving forward in this space, for screening and early detection?

Sigrid Carlsson: That's an interesting thought in terms of scalability. If we were to introduce population-based screening and do we have MRI machines and do we have radiologists to read them? Because that we know that who looks at the images can really make a difference. And so when is the prostate MRI normal or what's the negative predictive value of prostate MRI can depend on how it was performed and the machine and also the reader. So, can it be accurately done at all centers if we were to introduce MRI as part of the screening pathway, is an interesting question. And so, can we use ultrasound instead? I don't think that has been studied in terms of prospective screening studies, but it's certainly an interesting question going forward if that is an imaging modality that could maybe be used and could be in the hands of experienced urologists. Yeah, it's an interesting thought.

Phillip Koo: Great. You bring up a great point about MRI and some of the limitations facing MRI. We've heard about a lot of the struggles in inter-reader variability and referring physicians not feeling very secure or the results being reliable. AdMeTech and the work they've done with PI-RADS has obviously been very pioneering. Where do you think we stand today with regards to that issue regarding the interpretation of prostate MRI?

Sigrid Carlsson: Yeah, I think it's a point well taken. PI-RADS absolutely following that system and also training of the readers and radiologists. I always say, "A chain is always as strong as its weakest link." So the whole chain needs to work, which is the urologist performing the biopsy and the radiologist reviewing the images and the equipment, what you have, and the pathologist also reading the biopsies. So it's like you need that whole chain to be well functioning and it's like a well-oiled machinery that where you have the training and the expertise for this concept to be successful, because, to your point about the variability, maybe these excellence results that we have seen in the large scale trials might not be generalizable to the community for population-based screening. But, on the other hand, the PSA test was a simple blood test, which is you get a value and level. So it doesn't have so much reproduce ability in variation in that. There are a lot of interesting concepts when you think about screening and population-based screening, if you can translate the results from these excellent trials.

Phillip Koo: Great. You're the world's expert on this topic, you know more about this than anyone else, and if you sort look into your crystal ball five years down the road and what the potential solution might look like, can you tell us what that would be, and maybe it could help direct some of the efforts occurring globally to make that vision a reality?

Sigrid Carlsson: Oh, good question. There are a lot of things we can do that are very simple, I would say, if you want to keep the benefits and reduce the harms of screening. So we don't have to have super complex methods or studies or solutions, but the good old PSA is very good. We start with a PSA test and it's still an amazing marker of prostate cancer. If you look at that predictive accuracy and it's ability to predict risk in the future of life threatening prostate cancer, the area under the curve, it's 90%. So it's a really good screening test. I don't think we should abandon PSA. That's our first starting point.

The other thing that we can do to reduce some of the benefits, it's not to over screen elderly men or those with comorbidities and focus screening on men in midlife and those at increased risk, African American men and those with family history. So if we can shift what we're currently doing to focusing on those at greatest risk and who might have the greatest benefit, we have a lot to gain just from doing that.

I would say start with the good old PSA, and then use some sort of risk stratification before proceeding to biopsy. Back in the days, if the PSA was above 3 or 4, we'd just jump straight to biopsy. But I think that's old practice. So now, whatever people use, whatever they feel like, it's a biomarker, whether it's pre-biopsy MRI, whether it's a combination of those things, it could be a risk calculator, some people use that, and the risk calculator that's been developed in your population if it's in the U.S. or in Europe, but something, some sort of risk stratified approach. It could be do an ultrasound and prostate volume, volume is a great marker, or some other reflex tests that can be used together with PSA, and then jump to biopsy if it's indicated. And then also simply repeating the PSA test, because we know that the PSA test can fluctuate. Those are very simple things to do. And then the biopsy, who performs the biopsy. We have methods now and better techniques to do more targeted biopsies and more precise biopsies to mitigate the side effects of that.

It's almost like a pyramid. You start with the PSA test. And also, I shouldn't forget to mention our own studies that show the value of a baseline PSA to exclude men from screening. Because we know that if your PSA level is less than 1 at age 60, the long-term risk of developing metastatic disease, of dying from prostate cancer, is very, very small. It's 0.2% at age 85. So that means you can exclude almost 50% of men from additional PSA testing if the PSA is less than 1 at age 60. So that's also incorporated in our guidelines at MSK and that's another very easy, simple principle. So if you have that pyramid, again, PSA test, risk ratification, with or without MRI, and then proceeding to biopsy, I think that's how you can keep the benefits and reduce some of the harms.

Phillip Koo: That's wonderful. It makes a lot of sense and it really provides a nice roadmap for how we can solve this problem. For those of you who are interested, please make sure you join, register for this meeting. I think it'll be a great session. Thank you so much for joining us.

Sigrid Carlsson: Of course.