Alicia Morgans: Hi. I'm so excited to be here at AUA 2022, where I have the opportunity to talk about the new AUA localized prostate cancer guidelines with Dr. James Eastham and Dr. Steve Boorjian. Thank you so much, both of you, for being here today.

Stephen Boorjian: It's a pleasure to meet with you.

James Eastham: Thanks for having us.

Alicia Morgans: Wonderful. So why don't we start just by setting the stage, really, and trying to understand how these guidelines are put together, because they are compiled a little bit differently than things like the NCCN guidelines. And it, I think, is important to just put that out there so that we all understand how they're developed. So why don't you start that off for us, Steve?

Stephen Boorjian: Sure. So the guidelines are developed after a panel is put together by the AUA and panel chairs with multispecialty representation. This one was done in conjunction with Astro, as well as representation from the SUO and ASCO. The panel defines a set of PICO, or guidelines, sort of questions to define the evidence base that will then lead to a systematic review, methodologic review, that's conducted by a group out of the Oregon Health Science University. That group puts together a systematic review based on evidence comes back to the panel with that. And then the panel bases its subsequent recommendations, guidelines, statements upon the levels of evidence that were determined from that systematic review. And those levels of evidence are actually graded by the methodologic review as A, B and C, and they lead to the strength of different recommendations that come from that.

Alicia Morgans: Well, thank you, because I think that's so important as we think about how did the guideline statements, how were they constructed? And it's really based on that systematic review, which is external to the panel, but of course, is integrated and considered by the panel.

James Eastham: Right. The quality of the evidence really guides how we structure the guideline. So, many studies are older and they're based on particular levels of evidence that perhaps newer reports just don't have the quality of evidence available to be incorporated into this type of guideline. So it is structured in a format that's a little different, as you mentioned, than the NCCN and other types of guidelines.

Alicia Morgans: Well, thank you, and I'm glad to know that we have such a strong evidence base, or at least that we understand the strength of the data that is used to integrate into these guidelines. So really, really helpful and important. And so I'd love to hear from both of you, there was a lot covered in this guideline. What are your highlights?

James Eastham: I think one of the highlights is really a continued emphasis on shared decision making, that patients need appropriate information based on their individual setting, based on their age, their comorbidities, et cetera, and the risk of their cancer, and the risk of the treatment of that cancer in order to make a decision that is best for them. So we continue to emphasize high quality data, looking at outcomes, not only from the quality of life standpoint, but also from the cancer treatment standpoint. So I think that was one area of emphasis.

Alicia Morgans: And that's great. And I should mention, too, that there's a patient representative on the guideline panel, which I think is also really important.

Stephen Boorjian: Right.

James Eastham: And many of the comments we receive, so the guideline once it's formulated is sent out for peer review, and many of the peer reviewers are patient advocates. And so their comments were deeply appreciated and they helped formulate the final product, which we think certainly improved it in the end.

Alicia Morgans: Absolutely. And Steve?

Stephen Boorjian: Yeah, I thought two highlights that I took away from the guidelines were the use of a risk stratification system to help with the shared decision making. So the risk groups allow counseling on patient disease risk, and that gets put into the shared decision making with patient factors, prioritization, risk tolerance. And then the second highlight that I took away from the guidelines that I really think helped separate them were these sections on principles of management. So there was a section on principles of active surveillance that are aimed to help clinicians take care of patients on active surveillance, providing how these patients should be followed. Same thing for surgery, some principles of surgery. And the same thing for radiotherapy, some principles of radiotherapy that are sort of guiding the practical every day. How do we take care of these patients in different risk groups with all of the different management strategies that we have available for clinically localized disease?

Alicia Morgans: Go ahead.

James Eastham: I was just going to say, in that vein, certainly the section on active surveillance, and actually a strong recommendation and endorsement of active surveillance for the vast majority of patients with low risk prostate cancer. I think we solidified that section quite well. And since the last guideline, which was about five years ago, there have been significant improvements in techniques for radiation therapy, and our colleagues in radiation oncology really strengthened that section and really updated it. So I think that even though it's an AUA guideline, it's important to emphasize it was really a partnership between the AUA and Astro to generate the final product.

Alicia Morgans: Absolutely. And one of the other things that I think is so important is that it's not just the guideline statements that really communicate the depth of knowledge and the guidance that's in this document. There was a significant amount of effort put into the discussion sections, which really round that out, and as you said, these sort of focuses on and tables on how to do things in everyday clinical care. Do you have any comments or thoughts on highlights in the discussions that really bring out some nuances that didn't necessarily make it to the high level of evidence of the statements themselves?

James Eastham: I'll make a general statement, and then perhaps some specifics from Steve. But if someone uses the guidelines and simply reads the clinical statement and does not go into the discussion as you appropriately mentioned, I think they're missing the point of the guideline, because there are a number of nuances based on how we generate the guideline, evidence based, literature review, et cetera, that would get lost if you simply just read the clinical statements. So I think it's important to take a little bit of time, really digest what the panel was trying to convey in terms of each of the statements. but the discussion's quite important in rounding out the entire document.

Stephen Boorjian: Yeah, I would extend that to say the discussion really is a reflection of the work of the panel. The panel members put a tremendous amount of time and effort into it, and it does offer context for the guideline statements. It, in many cases, offered an extension of what may be coming on the horizon, acknowledging the state of the limited evidence in maybe one or two areas, and saying, "Where made this be going next?" So, to James's point there, if you just read the guideline statements themselves, it's not enough, and I think you'll be left sometimes with questions about, "Why were these developed? How were these developed? How should I manage?" And many of those answers are actually in the text, as well as a look at what's going to happen next, I think.

James Eastham: Right. Guidelines, they were based on a literature review at the end of 2021, and some have said, "Well, guidelines are outdated before they get published." And that's true to some extent, but if you read the text, it really addresses that particular point, as Steve was saying. There's lots of things that are on the horizon. There's new research being published every day, and there's certainly more to come. And I think the exciting part, for me anyway, about being on the guideline panel is knowing that the guidelines will be updated, and that will ultimately improve patient care and how we deliver patient care to patients with clinically localized prostate cancer.

Stephen Boorjian: Yeah. I was going to say, I think one of the other unique features of the AUA guidelines is that they are continually updated. So the AUA, every one to two years, does a look at what's been published, what's new in that area, and does an assessment on whether guidelines need to be revisited and re-updated. And for multiple guidelines, you can see that the AUA has issued updates as new and important practice changing information comes out. Again, it's based on an assessment of the state of evidence and a systematic review, but it's, I think, one of the unique strengths of the AUA guidelines, is that it remains a working document that gets modified in accordance with new evidence.

Alicia Morgans: I would agree. So as a member of the panel this time, I really was impressed with the way that we were able to incorporate new data, but we couldn't do it necessarily in the guideline statement at the time, because the evidence base and the grade assignment was actually done so long previous to the guideline development. So we absolutely incorporated that into the discussion. And as you said, it's a look forward to the future, and certainly people can learn and use the discussion as well to inform their daily practice. They can go beyond the statements themselves.

James Eastham: Indeed. Yeah, I think there's a couple of areas, genomic classifiers, molecular imaging, that are quite popular in terms of discussion, and they generate a lot of preliminary data, but the level of evidence to incorporate them as a standard of care, the evidence just doesn't meet that threshold in this particular guideline, just based on how the guideline is formulated. And that's an area of future directions. And we certainly address that within the text of the guideline, that we certainly understand that this level of evidence is not currently there, but we expect it in the very near future, and the guideline will be updated appropriately as the level of evidence suggests that it should be.

Alicia Morgans: Wonderful.

Stephen Boorjian: And we also recognize that the guidelines provide a framework for care and some instructions, but clinical judgment and people interpreting new data that comes out even after the guidelines is going to be used in clinical practice. So it's by no means to say that these guidelines are the end all of how people should practice. We recognize the importance of people incorporating new data as it comes out, people using their own clinical judgment. And the hope is that the guidelines provide a background and framework to help shape care that way.

Alicia Morgans:  Well, I think they absolutely do. And I'd love to give you each the opportunity to give one final comment on this phenomenal effort. And congratulations on making it happen. Go ahead, James.

James Eastham: Sure. I think I'll just expand a little bit on what Steve said. I think that guidelines provide a framework to have a conversation with a patient about their individual situation involving risk assessment, not only from the cancer standpoint, but also from the treatment standpoint, and having a conversation about which of the different treatment pathways, be it active surveillance, surgery, radiation therapy, what their outcome might be and why they might want to consider this rather than something else. And when I'm chatting with patients, I very frequently say, "I could have your prostate twin sitting next to you, give you all the same information, and one of you may pick one treatment and the other may pick another, and you're both absolutely right." And it's how an individual will weigh different aspects of their care, whether it's the treatment or the treatment related side effects. So I think the guideline provides the basis. Again, not the be all and the end all, but it provides a basis for having that conversation, which certainly, in prostate cancer, is important. And that will improve patient outcomes, their happiness, if you will, with their treatment decision.

Stephen Boorjian: Yeah. I think that, in a very similar vein, I would say that the intention of the guidelines is to frame a "how to," not "what to." It was not intended to say "X treatment better than Y treatment," or provide comparative assessment. It was more to say, "Here's the framework of what you should be discussing with the patients, and should you choose treatment X, Y, or Z, here's some guidelines on how to execute that treatment." So it's more providing a background and information to guide that discussion with the patient so that they're as comfortable as they can be with their treatment choice, and so that the clinician is provided with as much information as they can be about how to go about each one of the different treatment modalities.

Alicia Morgans: Well, I sincerely commend both of you. It was a labor of love, that is for sure. And it has provided a framework for us to make sure that every patient with prostate cancer really has the opportunity to have the highest level of care out there and to really get the best outcomes for each individual. So thank you very much for your time and your expertise.

James Eastham: And thank you. And you contributed as well. So thanks very much for being on the panel.

Alicia Morgans: Thank you.

Stephen Boorjian: Yeah. Thanks for having us.