Read the Full Video Transcript

Gordon: I have the distinct pleasure of inviting Dr. Eggener to the podium to give us a discussion around leveraging cutting-edge technologies in the management of prostate cancer patient treatment options. He's the professor of urology at the University of Chicago School of Medicine, the vice chair, Section of Urology, and he currently is the director of High Risk and Advanced Prostate Cancer, a prolific academic surgeon, and an all-around great human being. So, thank you, Scott.

Scott Eggener: Thanks, Gordon. I know close to nothing about BPH. There were two great things about that session. Number one, we got to listen to three big brains talk about BPH, and number two, it's one of the few things that is now going to make prostate cancer decision-making seem really simple. How do I... Oh, here we go.

So I was excited when Dr. Hafron and Brown asked me to talk about this topic. It's not something I've spoken about before, so it was fun to put together. I'm presuming I speak for many of you in the room, technology and innovation is one of the things that was really attractive when you decided to go into urology, and now is a super exciting time and I just cover some of the things in prostate cancer. And it's going to be kind of a quick whirlwind through, and it's just one person's thoughts. There's a lot of controversy about what's good and bad, what we should pursue versus not, but I want to run through these things, at least from my perspective.

These are my disclosures, and I put boxes around the ones that are either directly mentioned in my talk or even peripherally mentioned. Even amongst the boxed ones, some of those, there is no financial element, but I've been an investigator in some of the trials or I've advised the company, sometimes for nothing, and then some of these are just one or two visits with them. Probably the one where I've been most involved with was Profound Medical, where for a couple of years I was on their advisory board, and ultimately the principal investigator of their registration trial for TULSA.

This is just kind of the grand overview of what I want to go through. I'm going to start with the famous Irish poet, public intellectual, alcoholic. Fun fact, one of the only two people to win a Nobel Prize and an Academy Award. But we all need to try to embrace progress to some degree, and that's one of the fun things in our field is that it's hopefully always changing. Now, my intent is not to be acrimonious with this, but I want to be honest in my thoughts. Some of these things are really exciting and some of these things I'm a little bit more sanguine about, and you have to be kind of balanced in what to embrace versus what not. It is easy to be wowed by new things. I think it's part of our kind of operating system. And it's also, in our brain, easy to be hijacked by things that may not be so important for patients, and I think it's important to temper some of the enthusiasm sometimes.

My personal thought is if you're always the first adopter or the last adopter of something, you probably want to be somewhere in between, and whatever fits you and your practice and your patients is probably best. I hate to sound like the ivory tower knucklehead here, but it really all comes down to kind of data and evidence on value for patients. There are certainly a lot of other ancillary things that are important—ease of use, reimbursement, other things—but ultimately, I think the single most important is for the patient. And more isn't always better. We have a unique healthcare system where we can easily pile on a lot of very expensive, fancy tests, sometimes nominal value, sometimes dubious value, and sometimes legit value. And I think it's important for us to always investigate in an honest way what those are.

So I'm going to go through different clinical stages. Screening, great news. There are a lot of tests out there that absolutely, positively outperform traditional PSA. The good news is some of them are easily accessible and cheap, some of them are more expensive, and I'm not going to go through them all except to tell you that, in general, they lower the likelihood of men needing a biopsy. You find nearly all of the men with grade group two or higher, which I think is the primary focus of screening. Try to find grade group two or higher and then decide what to do about it, whether you're going to treat or not. And you find fewer men with grade group one, which I think is a triple win for these guys. Now, I don't tend to order these regularly. That's the caveat. I tend to use free PSA, PSA, PSA density, things like that. There are absolutely times I order these, but it's certainly not a reflexive test, but there is absolute value in these tests.

I do think it's also important for us, as a reminder, to remember all the cheap free things that are at our disposal to make smart decisions with screening. I have a whole 30-minute talk on this. I'm just going to run through, in probably 30 seconds, things that I think are valuable. Not everyone needs a PSA. We've got a bit of an epidemic of sick old men getting PSAs. It's important to have some form of a discussion with a man before you start screening him, but that's more for the primary care physicians. Be familiar with the modified guidelines. We don't need to screen every man every year. Simple: always repeat an elevated PSA. I make the comment to our trainees, I'm not sure of any situation with screening, treatment, or post-treatment where you change the plan based on one new change in PSA. Always repeat it.

Never give empiric antibiotics. Thankfully, that's not done as much as it used to. Baseline PSA is gold. In their 40s or early 50s, take their baseline PSA, risk stratify them. Every single guideline says based on that, you see them back somewhere between one and four years. We need to do it like colonoscopies. You get your baseline colonoscopy and then they tell you when to come back. Same with PSA, before BPH becomes a confounder. PSA velocity makes a lot of sense. The disappointing thing is, when you look at it rigorously, it's not very helpful. There's been two massive studies where once you know everything else about that guy, the PSA velocity falls out of the equation. So use all the other things that you know about.

I think free PSA, if we could monetize it, commercialize it, sell it, it is better than total PSA if you look at the raw data. If someone asked me would I rather know my total PSA or my free PSA? I'd rather know my free PSA. Every single person I screen, I get a free PSA on. PSA density is really powerful. There's a wonderful graph that I usually show. I think one of the greatest values of the DRE is getting a sense of small, medium, large, extra large, or double XL to make decisions with PSA density. And there is great data on when to stop PSA screening. So if your PSA is less than one at age 60, likelihood of needing something down the road is about 0.2%. That's your risk of dying from prostate cancer, and a 0.5% risk of metastasis. So dial back or even stop and document it in the note and we can save a lot. So that's my soliloquy on that.

Imaging. All right, MRI has taken over. MRI is a win. I order a ton of MRIs. There is value. But they're good, sometimes great, and rarely perfect. This is the epicenter of MRI imaging of the prostate at the National Cancer Institute, and not only great radiologists, they combined in this study with artificial intelligence. I only mention this to you, that MRI is really helpful, but it's not absolute, and it's important to know when you're thinking about extracapsular extension, either surgically or surveillance versus treatment, look at those operating characteristics on sensitivity and specificity. There are many times MRI can mislead you. So integrate it into your decision, but rarely, if ever, make it the end all, be all to guide the decision.

There's a lot of cool technology and innovation to make MRIs even better. I'm fortunate to work with a great MRI group. We've published a bit on using artificial intelligence with MRI. It's a 10-minute scan. We get some of the other sequences out of it. You can see some of the pictures there. In an early study that we've published, it appears to be more accurate and fewer people needing biopsies.

Here's some fancy pictures on picking up things that weren't picked up on traditional MRI, and so we target other areas based on the artificial intelligence. Here's the data from the 91-person study we did at our site. You can just simply see that hybrid MRI, the operating characteristics are better than a standard mpMRI. We've rolled it out to a couple other centers. We're doing a multi-site trial. We'll see if it pans out or not. Similarly, out of UCLA, Lenny Marks has some great data on using artificial intelligence with MRIs spun off a company called Avenda. I've consulted for the company, I've made $0 for them, I have zero equity, but there's some pretty cool stuff coming out of there. And you can get these great pictures that give you kind of heat maps on likelihood of extracapsular extension, and they have all sorts of stuff that match up with whole mounts. And they tailor it for individual patients and the system that you use to do your biopsies.

Now, what's better for extraprostatic extension, MRI, PSMA PET, or both? There are many studies out there, I'm highlighting one from Indiana University, where they looked at patients with intermediate or high-risk disease. They went to surgery. Let's use both of these to guide nerve sparing. Look at the whole mount. Which was better? Clear winner, PSMA PET. Now, it would be wonderful if PSMA PET was cheaper, easier, quicker. I'd love to order it on all my patients from surveillance on up. I don't because, at least at our place, I'm told it's a $7,000 test and I try to be at least, at times, cost-conscious with it. I hope there's a time where we order it more regularly.

And also remember with PSMA PET, I sometimes hear docs say, based on a PSMA PET or even an MRI, "I mean, that showed a node, that showed extraprostatic extension," and they talk in absolute terms. It's rare to find a test that has absolute data. And so again, just being a little bit more tempered. Here's the data that led to the FDA approval of PSMA PET. UCSF and UCLA, 277 men, and if you look at the sensitivity of finding nodes on PET, it only picks up about 40% of the nodes. So just because it doesn't show a positive node, many times there are.

And on the other side of the coin, just because the PSMA PET lights up in a node, it's only real about 75% of the time. Now, there's some other studies that have shown that PPV being a little bit higher, but something to remember. And also remember with PSMA PET, in general you want an SUV above five before you start getting cocky about whether there's prostate cancer there. There's an equivocal gray zone of kind of two to five. There's a larger meta-analysis where the sensitivity is higher for picking up nodes. So it always depends on what kind of patients you put in the study and what your gold standard is. But just remember, it's not absolute. I use it a lot in patients, but it's not the end all, be all.

This is one where I first read, it kind of scrambled my brain. Like who are these charlatans? But I mentioned this in a technology innovation talk to ourselves that there are a lot of things that you once heard of that you thought were crazy and you now do probably every day or every week. And so you have to have an open mind. This was a group out of Germany where they took people with PSMA PETs that were positive, did not do a biopsy, and took them to surgery. And that sounds looney tunes, but it was less than 1% of their patients. They claimed, and I will implicitly trust them, that the patients had informed consent. And sure enough, at prostatectomy, they all had grade group two or higher, and you can see the pathologic characteristics there.

We were asked to write an editorial on it and I kind of struggled. Do you call these people out and push back? This is how I took it. Is this something we're all going to be doing one day and they're pioneers, or is it something none of us will ever do? You've probably all heard this quote at the bottom in one form or the other, and it's a good reminder, particularly when you're thinking about new technology or new innovation. Try to have an open mind, try to be skeptical, while at the same time embracing things and trying to learn more about it.

Prognosis, staging, and management. We've got a lot of genomic tests out there. Okay? I don't have any ties to any of them. I would tell you that I think the single best one, based on extensive validation, really good science, is Decipher. That being said, I do think it has value in certain clinical situations. If a guy is really struggling between surveillance and treatment and you're looking for something to tip the needle a little bit, but it's not the end all, be all, it has potential value. If someone is considering radiation therapy and has a low-risk Decipher score and might be able to skip ADT, great. There's data to support it.

That being said, now I'm going to give you my salty side. I think this test is way over-ordered. It's a $5,000 test. There are urologists around the Chicago area that every single patient diagnosed with prostate cancer gets a Decipher score. I see a ton of patients where I say to myself, "Why did they get this?" No matter what the Decipher shows, you're not going to change a darn thing in your counseling or your management for that patient. So try to be reasonable about when you order it. That being said, it's a really good test. The ASCO guideline, the AUA guideline, say the same exact thing. High-quality test, but try to pick patients where you think it might have potential value.

Artera. It was mentioned earlier by Dr. Jayram. This is basically artificial intelligence on prostate cancer biopsies in a radiation cohort where it has shown a signal. And this is a study that I asked some friends at UCSF, this has been in abstract form, not published, but basically they looked at tissue microarrays from prostatectomies and you can see artificial intelligence colors it up, does some things behind the scene on the computer. And interestingly, above and beyond the CAPRA score and what you already know, it can independently predict BCR and metastasis.

Now, whether it has value at some point down the road. I would say, some of the time, does it really matter if someone's BCR risk is 30% or 50%, if you're still going to treat them anyways? Is it going to change anything? So you need things that not only change what you do with a utility test, meaning it changes your management, but that the outcome is better. Or the outcome is worse and that's how we learn from things.

Circulating tumor DNA. This is kind of in the same category as circulating tumor cells, but this is just free DNA, cell-free DNA that you can measure. It makes a ton of sense and there's good data in urothelial carcinoma that Dr. Jayram had mentioned. We're not there in prostate. It would be great if we had this version of a liquid biopsy. Probably one of the best studies that's been out there. Patients going to prostatectomy, now, with current technology, only 16% of them had measurable circulating tumor DNA, but it did seem to be a signal. That's great, looking at the signal. But then if you look at the fine print, it wasn't any better than Gleason score. So we have a lot of good tools already. Hopefully in the future we can get CTCs or circulating tumor DNA.

This is an exploding space with new isotopes for theranostics or imaging in prostate cancer and elsewhere. This is a laundry list of things. Actinium, which is a beta-emitter, lutetium, you've heard about, and many others. Big companies have invested a ton of money in this space. It's exciting. There's something called scandium. We've worked with our colleagues at Argonne Laboratory, which we have a relationship with. We've given them some money to run with things. Scandium, there's a lot of excitement about because it has a longer half-life, so there's not as much of a rush to image. There's less off-label targeting. So there's thought to be potentially less side effects with some of the theranostics.

And then lastly, moving into treatment. So again, there's a lot of visceral opinions on focal therapy and a lot of blowback. I would just remind us that sometimes history reminds us that we can be wrong in certain things. And as someone who has taken an interest in focal therapy for many years, I've done a lot of reading about breast cancer focal therapy, and it's fascinating, and I can make a very compelling argument to you that we're almost exactly 50 years behind the breast cancer community in each of these steps. And if you read the history of breast cancer focal therapy, which is now in longstanding standard of care, the early adopters of that were called assassins, committing crimes against humanity, shouted down, "Can you believe they were doing this?" And then sure enough, randomized trials showed value, and nowadays about 60% of women with breast cancer get lumpectomy, also focal therapy.

I know there was a talk earlier today about it, so I'm not going into a lot of details except to say we're making progress in prostate. And when I say making progress, I mean we're studying it more rigorously and there are randomized trials going on. I have absolute confidence there's going to be a subset of patients where focal therapy is a very reasonable option. It worries me that there are, perhaps in your community, and many of them, there's charlatans out there that are going to offer focal therapy to everyone; it can be upwards of $30,000, and we need to try to, if it's even possible, to limit that.

Here's a form of kind of focal-ish therapy, but something interesting. And I am with this company, the PI of the trial, I haven't received a dime and I have zero equity in the company, but we have a randomized trial on intraprostatic immunotherapy where you basically inject into the four quadrants of the prostate. It's inert and it's a genetically engineered adenovirus. It's inert until they start taking valacyclovir. They take a course of valacyclovir and it activates what's going on in their prostate, stimulates a T-cell response. And the cool thing is we enrolled people in a trial, and it was a randomized trial for men on surveillance, fully accrued, we've got three-year follow-up, and over the next few months, we're going to unblind the data and see if there's value there. So maybe possibly... There's also a massive, much bigger phase three radiation trial where they did it that will be reporting about the same time.

There's a bunch of new robots out there. Obviously, that's been a major advance in our field. They're all over the place and it's been really helpful for patients. There are competitors from many other countries that were touched on earlier today in a talk that I assume most of you were at. There's a lot of potential for improvements.

I hate to be the Debbie Downer, but here's kind of what I think is somewhat typical, but a black eye on American medicine. You can build something that's super expensive, you can advertise and market the heck out of it, you can make a fortune, you can bilk insurance companies. And then finally, 30 years later, someone does a trial that is just now in abstract form, it will be published. Proton therapy is exactly the same as regular radiation therapy, IMRT, for prostate cancer. It's not any better, it's not any safer, there's not less side effects. But you can draw fancy pictures, and certainly from a physics standpoint, it's supposed to be better, and it pains me to think how much money we, even as taxpayers, have spent on this. You know the story.

I mentioned this to you because hypofractionation wins the day. These are from guidelines. Everywhere from low risk, which should probably almost never be treated, to high risk, the guidelines suggest some form of hypofractionation, moderate to ultra. I don't mean to be the mean guy here, but if in your practices or your radiation oncologist, your patients are getting six to eight weeks of radiation therapy, there's only one benefit of that six to eight weeks of radiation therapy and it's not to the patient.

Five takeaways, because Dr. Brown asked me to wrap it up in five. So seek newer and better ways. Embrace it. I mean, you don't want to become that old cranky doc that we all knew when we were training that is still doing things from 20 years ago. There's a ton of exciting things out there. And this was just a whiteboard, splashing some things up. Try to be sensible about things. Don't be a sucker. And if it's amenable in your practice, I certainly try to do this, where if there's an opportunity for a trial to study something before just widely embracing it, I think that's always preferable. And particularly in LUGPA, where there's a super impressive clinical trial mechanism that outdoes even many places in academic medicine. So thanks for listening.