"This [guideline]... is probably the most broad in scope and incorporates a lot of the things that were missing or not yet mature enough to be included in the previous guidelines," says Badrinath Konety, MD, MBA.
In this interview, Badrinath Konety, MD, MBA, discusses key points from the American Urological Association (AUA) guideline on the early detection of prostate cancer.1 Konety is a member of the AUA prostate cancer guideline committee and the president of Allina Health Cancer Institute in Minneapolis, Minnesota.
I have been part of the prostate cancer detection guideline committee for the past 2 iterations. I was on the previous guideline and on the guideline before that. So, this is a guideline that evolved over time. This one, I would say, is probably the most broad in scope and incorporates a lot of the things that were missing or not yet mature enough to be included in the previous guidelines. By that, I mean imaging, like MRI, was not mature enough to be included in the previous one. There were lots of markers available then, but the data were not mature enough to figure out exactly where some of the secondary markers for prostate cancer beyond PSA fit in. So, most of the previous guidelines were a PSA guideline, [on] when to use PSA to detect prostate cancer more than anything.
They've done a great job of broadening the scope of the guideline to incorporate some of these other tools and exactly how they fit in to diagnosing prostate cancer. We've come up with 3 algorithms that are easy to read and follow in 3 different scenarios for patients. The guideline was divided up like that, [by] initial screening decision—somebody who's never been screened for prostate cancer—and then once you decide that you're going to go through screening, you have an elevated PSA, or other elevated risk for prostate cancer, what's the next step? Then you undergo an evaluation for prostate cancer, which turns out to be negative. What do you do after that?
So, there are 3 different clinical scenarios that we used to say, "Okay, let's address each of these." They specifically addressed MRI. We've addressed biopsy techniques, and also where to incorporate second level markers. We've also made comments on how [to] apply previously used parameters that triggered diagnostic evaluation for men with elevated PSA. One of the drivers for prostate cancer diagnosis used to be men who had been followed with serial PSA, [and] when PSA velocity went up, that triggered further evaluation by urologists and possibly biopsy. We have addressed that as well.
I would say [one of] the main things is the age to initiate PSA-based screening for prostate cancer. We still recognize that PSA is probably the primary tool for prostate cancer screening, and we acknowledge and respect that at this point. There is not another tool that is a better one than PSA as the initial test for identification or determination of prostate cancer. We acknowledge that, and then we went from there. As you know, we've used a standardized evidence analysis, a standard PICO document to collect the evidence, grade the level of the evidence using the AUA strength of evidence category, and we used a non-employed independent analyst who went through all the data and gave us the results, which the committee then sifted through and formulated the guidelines, using that as a basis.
The other thing is not only do we grade the level of evidence, but we also grade the strength of the recommendation. We use the grade approach, if you will, to analyze and formulate the guidelines. So, there's a dual certification of each guideline. We have recommendations that are strong, moderate, and conditional. Then we have clinical principle and expert opinion, where we have very little strong evidence, certainly no level 1 evidence at all, so [these are] areas that are gaps that we're trying to fulfill by using the expert knowledge that's on the committee or certain clinical principles that are defined.
Initial screening for prostate cancer, just like in the previous iteration, we stress again that shared decision-making is key. It's not that the prostate cancer screening is automatic in every person; there has to be a shared decision-making, understanding the risks entailed by such screening. It's like opening a Pandora's box; once you start screening, potentially there's a drive to take action, especially if the screening results suggest that there is a risk for prostate cancer by an elevated PSA. That may trigger a biopsy, which may potentially have a risk for complications, which may subsequently also trigger consideration of treatment, which should be judiciously used. You don't want to overtreat people who don't need treatment, and undertreat those who need it. There are some discussions that have to be had there, but I think it's important upfront to make the patient aware that there's controversy about prostate cancer screening. A man can [choose to] undergo prostate cancer screening based on their own preferences and risk assessment, and be aware that if we undertake this path, then there are certain next steps that may emerge that they will have to make additional decisions in a thoughtful manner.
The other thing I would point out, we acknowledged in this guideline, that there are transgender and other folks who need to be included. So far, we have not paid attention to people who are transgender. Men who become women but who still have native prostates left in there. We still need to include that population. So, if you look at the guideline, there's a lot of reference to "people" or "patient" but not "man,” or so forth, because there could be different people [and] we shouldn't forget them. We need to make sure we're aware of them as well.
We also said that the age to initiate screening previously was 55 to 69. Then we even said 50 could be okay. But here, we've lowered the age to initiate screening to 45 to 50 years, and then if somebody has an elevated prostate cancer risk, which obviously is defined as strong family history [and] Black ancestry, to initiate screening at the age of 40. We've decreased the age of screening, which was one of the big issues that people had with the previous guideline, [that] the age to initiate screening seemed to be rather high. Again, if you read through the guideline document itself, there's lots of basis behind this.
The other risk factor we also had to consider is germline mutations, such as BRCA. We felt that there is strong evidence, and it's a strong recommendation to commence screening at age 40 in people who had these risk factors, Black ancestry, germline mutations, and strong family history of prostate cancer, which I think will be a unique and a new mention compared to the previous guidelines. Of course, we recommend PSA be used in the first test for screening for prostate cancer. We also recommended a screening interval just like in a previous guideline of 2 to 4 years in people who are 50 to 69 years of age. You could also personalize the screening interval based on the patient's risk. [If] you have a high-risk patient, then maybe you want to do a yearly screening interval. Maybe their lower risk or standard risk, you can go to a 2 to 4 year screening interval. In people who are getting their first PSA, we strongly recommend [getting] a complimentary PSA, to get 1 more PSA before you initiate any further action, particularly if they have an elevated PSA level. If they have a normal PSA level, it's okay, but if you have an elevated PSA level on your first screening intervention, then you need to confirm it at least a month out and then see what happens. This is in patients with average risk in particular. Then the DRE, [we] made it optional. Previous guidelines said the screening intervention consists of PSA and DRE, this time we said just PSA is required and DRE is optional. That's how we separated the 2 out, based on a lot of strong evidence from the European studies, particularly EurSPC.
Once we do perform the screening intervention, if a patient has an elevated risk for prostate cancer as designated by a high PSA, then we say at this point, use a risk calculator. You take the PSA into consideration along with other parameters, and you could use any one of the online risk calculators as well as the life expectancy assessment. We would say that in patients who have an elevated risk either based on just a PSA or 1 of these composite risk calculators that include PSA, percent-free PSA, age, race, family history, etc. You could [use the] EurSPC-based one, there's a prostate cancer [Prostate Cancer Prevention Trial]-based risk calculator. Any one of those that are available online can be used.
Then, you use those data and discuss with the patient what is their risk of having prostate cancer, particularly high-risk prostate cancer, or more aggressive prostate cancer, and then decide on the next steps in these patients. At this point, we felt it was also convenient and appropriate to bring up the discussion regarding secondary markers, particularly for patients with a PSA between 4 and 10 ng/mL. Are there other markers, whether it's a 4kscore test, phi, Exosome tests, or any one of these other second level marker tests. Or an MRI would be the other test that we recommend be discussed at these times. These are both optional at this point, but we recommend discussion of those as optional tests.
Clearly, when the PSA alone is high and no adjunctive biomarker is agreed upon, then you could certainly proceed to initial biopsy. If the biomarker is done and that also is positive, then also you can go ahead with further prostate biopsy. But if the adjunctive biomarker is negative, then you could have a discussion with the patient if the decision is made not to perform a biopsy right away, then certainly you go back to the repeat screen interval and within the next 2 or 4 years, you get another PSA and act upon it accordingly. Same thing works, you can get a prostate MRI, the prostate MRI is negative, the decision could be made to say that we're not going to proceed with a biopsy, particularly if all you see is a PI-RADS 1 or 2 lesion. But if there is a PI-RADS 3 or higher lesion, then you could go to a prostate biopsy. We do recommend that if you perform a prostate MRI, which is optional at this stage, that the MRI be read using the PI-RADS scoring system so that it is very consistent. It has to be a multi-parametric MRI to be able to do that, so routine MRI won't do.
The initial prostate biopsy can be done either as a targeted biopsy, if you have an MRI-based target, or if you don't have an MRI, then you just do a systemic biopsy. In patients who have an MRI and have an identified target, you can either just do a targeted biopsy and make the systemic biopsies optional, or you can do both. You can do a targeted as well as systemic because there is a small subset of patients in whom the systemic biopsy could pick up prostate cancer that's missed by the targeted biopsy. This number is very small and most often tends to be low Gleason cancer, so that's why the strong emphasis on performing systematic biopsy on everybody is not there. The biopsies can be done either transperineally or transrectally. I know there's a lot of data in the literature, and the group acknowledged the fact that there are some data suggesting transperineal biopsy may lead to lower rates of systemic infections in particular, but strong data are still forthcoming. So, at this point, we felt the data were not strong enough to sway one way or the other, but we acknowledge that there could be potential advantages over transrectal. Once that becomes more clear, we can place greater emphasis on that form of biopsy, but at this point, we cannot.
Then of course based on the results of the biopsy, the discussion has to be had as to how to proceed with treatment, if that's deemed necessary, and for that the AUA clinically localized prostate cancer guideline can be utilized. If patients' biopsies are negative, but they have atypical small acinar proliferation, or they have high grade PIN [prostatic intraepithelial neoplasia], then the decision-making will involve whether to perform a repeat biopsy. [If] you just have focal PIN, we said even if it’s high grade, it’s not significant enough to warrant repeat biopsy at that time. But any one of the other factors, the discussion has to be had with the patient about the need for repeat biopsy, because there is a substantial subset of these people who probably have prostate cancer that can be detected subsequently. So, that is the reason for having that discussion.
Now, following this, what happens if a patient has a negative prostate biopsy? They have a negative prostate biopsy, you continue to go back into the screening mode and can proceed screening with PSA every 2 to 4 years or you can personalize the screening interval; especially in a high-risk person, you could bring it down to 1 year. If a person has significant comorbidities, something has changed, their life expectancy now is thought to be less than 10 years, or if they have a personal choice that drives screening to be stopped, then you can stop screening as well in these folks. These folks, we can recheck the screening PSAs and utilize the risk calculators to reassess risk if the PSA is again elevated. That’s going to be important to continue to categorize patients regarding the risk of having particularly high-grade prostate cancer. This is another spot where adjunctive biomarkers and prostate MRI can be used.
Again, if PSA remains elevated on repeat, we think that an adjunctive biomarker as a default test can be an option. But in this situation, we would recommend obtaining a prostate MRI. In the previous case, in a new PSA that’s elevated, prostate MRI was optional. Here, we actually recommend getting a prostate MRI in this case, because patients already had a biopsy or evaluation in the past, which has been negative, so now before you proceed to another biopsy, you really want to reevaluate and make sure that the patient has a lesion. If he does have a lesion, then you can proceed to target that lesion. Again, the same parameters, the MRIs read with the PI-RADS scoring, if it's 3 or higher, then you go to repeat biopsy. If it's a 1 to 2 or no lesion, then you could consider an optional repeat biopsy, but there is no strong recommendation to proceed in that direction. If the adjunctive biomarker is positive, or if the prostate MRI is positive, then we recommend doing a repeat biopsy. Again, it can be transperineal or transrectal. You certainly would do a targeted biopsy if there's a target lesion. The systematic biopsy on top of that is plus/minus. You could eliminate that if there is concern for infection, or if the physician feels that's the right option. And again, based on the results of the biopsy, if it's positive, you go into a clinically localized prostate cancer guideline, if the biopsy is negative, but has ASAP or high-grade PIN, then you go into the decision-making mode and discuss with the patient that there still is a substantial risk of missed prostate cancer and we could consider repeat biopsy just based on that at some point in the near future. If the discussion is with the patient that the patient will not undergo any repeat biopsies or doesn't need one, then the patient goes back to routine screening.
That's how we've laid out the guideline. You'll see this in the narrative in detail. The paper has been published online. The papers have been divided into 2 parts…just for ease of reading and to be able to compartmentalize the material.
The change I will see is probably the earlier screening, particularly based on some of the risk factors. We're probably going to see more men who are younger coming in because of their family history, they're Black, they maybe have a family history of other cancers. We will see more of that. We will probably see more interest in men getting assessed for genetic risk, whether they do some kind of genetic germline screening study to make sure they have BRCA or not; greater awareness and need for that. [Also,] greater use of genetics and genetic counselors to see when should I get screened for prostate cancer. We'll see some of the earlier capture.
We will probably also see more men drop off at the other end who are thinking okay, if I'm an older person with a PSA that's slightly elevated, but a negative biopsy, and so either they won't get referred, or they maybe come in and decide not to. I suspect there will be some of these greater use of MRI in practices. It may not be routine in every patient, but I would say it will slowly become more and more accepted. I would say there's a distinction between the AUA guidelines and the EAU guidelines. The EAU guidelines actually mandate an MRI before a biopsy in everybody. We chose deliberately not to go all that way because we looked at the data pretty hard, and the data are not as complimentary as we would like it to be to make a mandatory statement or a strong recommendation for an MRI in everybody, especially for biopsy. But I think there will be greater adoption of MRI.
There will also be a greater adoption of some of the second level testing. I'm using both MRI and second level testing in my practice, but people who have not been using it as much are going to likely use it to a greater extent. Where I may change my own practice is even up front. Most often, the second level testing had been done and so you already had a negative biopsy. Now, before you repeat the biopsy, you either get an MRI, or a second level test or both. Whereas I think we may think more about bringing second level testing into the biopsy-naive setting, somebody comes in who has never had a biopsy before. Before we proceed to biopsy, we may do a second level test as a cheaper alternative to an MRI, because it is increasingly becoming evident that what we want to do is find patients with high-grade cancer.
The last thing I will mention is whether to go with transperineal or transrectal. I know there has been a significant move, at least at some centers, to transperineal biopsy. I think that has a role, but the data are not conclusive yet. At least 1 presentation at the AUA with a 700+ person randomized trial from Albany suggests that maybe the infection rates are not that different. There's some controversy there, so I think it's important for us to dig into this and understand if it's worth switching everybody to the transperineal, because it is more painful, it does require anesthesia, it has reimbursement implications, so it's not that simple. A lot of people are doing it in the office with local anesthesia, but it's not as comfortable as the transrectal biopsy.
I think this is a remarkable guideline. It's an enormous amount of work and scope that's been done, so I hope it's well received by everybody. I think within the next couple of years, when some of the other data come out, I think we'll need to change this or update it, particularly regarding MRI, second level testing, transperineal biopsy, all of these are hot topics right now. It's great advancement over the previous one, but I suspect there will be more very quickly.
1. AUA/SUO releases early detection of prostate cancer guideline. News release. American Urological Association. April 25, 2023. Accessed June 16, 2023. https://auanet.mediaroom.com/2023-04-25-AUA-SUO-Releases-Early-Detection-of-Prostate-Cancer-Guideline