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Treatment Protocol for Incidental Prostate Cancer After HoLEP

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And we have a panel today with Dr. Ashley Ross, he's an Associate Professor of Urology at Northwestern Medicine; and Dr. Amy Krambeck, she's the Chief in the Division of Endourology and Stone Disease and a Professor of Urology at Northwestern Medicine. And they're here to highlight treatment protocol for incidental prostate cancer after HoLEP.

Doctors, thank you so much for joining us today. As we get into this really interesting topic, Dr. Ross, can you speak about the incidence of prostate cancer that's diagnosed at the time of HoLEP? How does the detection rate compare to other surgical procedures?

Dr Ashley Ross: Yeah. Thank you very much for having me. Essentially at the time of HoLEP, a large portion of the prostate is removed, maybe about 80% of the prostate is removed. And because of that, incidental prostate cancer can be found, so prostate cancer that you were not expecting to be there. That rate is slightly over 10%. In our series, I think it's close to 13%. And that rate can be modulated by a couple factors. One of them being how much the gentleman had gone through screening prior to the procedure. We try to take people through that process and have a good sense of whether they're going to have prostate cancer or not that's clinically significant before they undergo the HoLEP. But it could be higher in some series where that's not done.

If you compare it to other procedures, the main other ones being transurethral resection of the prostate, where tissue is coming out at that procedure, but much less of the prostate is removed, and so the amount of incidental prostate cancer will be lower. A comparable procedure would be something called a simple prostatectomy, which is a more invasive, more involved procedure that removes about the same amount of tissue as a HoLEP. And there, the incidence is roughly the same. Other procedures done for enlarged prostates, either vaporize the prostate or don't take out tissue. And so, it's unclear what you're dealing with in those scenarios.

Dr Amy Krambeck: So, I would like to just add to what Dr. Ross already said, which is one of the major benefits of HoLEP is that we're not only removing prostate tissue to help someone urinate better, but we're also getting what I would call the ultimate biopsy. We're removing about 80% of the tissue, so all of that tissue goes to the pathologist. They look at it under a microscope, and then they can give us a true assessment of the presence or absence of prostate cancer in that particular patient.

Melanie Cole (Host): So, I love that you said a true biopsy. It really is an excellent way to detect and you really get a good sample. Now, how do imaging modalities factor in, Dr. Krambeck?

Dr Amy Krambeck: I utilize two different imaging modalities for my patients. So when they come to see me for a HoLEP evaluation, the first thing I want to do is to ensure that this individual does not have underlying prostate cancer that is contributing to their symptoms. So, you know, they get a rectal exam, they'll have a PSA checked. If anything is out of the ordinary, then we will get an MRI. And MRI of the prostate can give us a lot of really good information about the interior textures of the prostate. We can look for abnormal lesions and if there's any abnormal lesions present, then Dr. Ross would do a targeted biopsy, which he can talk a little bit further about. If their initial workup's entirely negative, then I will just get a CT scan of the pelvis to get a sizing of their prostate. And generally, that's all that individual will need.

Dr Ashley Ross: I just want to add a little bit to what Dr. Krambeck is saying. It's important to note that it is excellent at a time of HoLEP that you get out so much tissue, which all gets processed and analyzed through pathology. The men should realize, and we are going talk about this I think later in the podcast, that a lot of the prostate cancer tends to live in the peripheral zone. And sort of what Dr. Krambeck's also saying is it's good to do these assessments of the whole prostate, including that peripheral zone before you go to HoLEP, so you can make sure that if you find cancer at HoLEP, it is usually the cancer that was in that more centralized area of the prostate as opposed to having like a tip of the iceberg kind of scenario where you're finding just a piece of the cancer that's mostly in that peripheral zone. So, that prior to HoLEP workup she's talking about with an MRI and potential biopsy is important for individuals that might be at risk to know that they're going into a HoLEP with what we think is either non-cancerous tissue, benign disease or with clinically insignificant prostate cancer, for example, small amounts of low-grade disease.

Melanie Cole (Host): Such an interesting detection modality as well. Now, Dr. Ross, tell us about the formal protocol that you both developed for managing prostate cancer after HoLEP and why is active surveillance sometimes the right approach.

Dr Ashley Ross: So actually, when Dr. Krambeck came to our practice, it was kind of early in my exposure to HoLEP. So, I think that just to step back for a second, the procedure is probably going to be, I think, the most commonly performed enlarged prostate procedure as time goes on, because the procedure itself is the most efficacious. When it's gone head-to-head with other procedures, it has the best combination of efficacy, safety, and durability of all the outlet procedures.

Now, the issue was that there was very few experts like Dr. Krambeck that were performing this at a high level. And so, people like me who are sort of getting towards mid-career had not really seen a lot of HoLEPs. But the new generation that she's training is going to do this more and more often. As we're removing all this tissue, we were finding all these incidental cancers and the question was how do we make a protocol and be thoughtful about how to follow these men.

Now, as was noted, about 80% of the cancers that we were finding at HoLEP were going to be lower grade cancers. And those are cancers that we really should think about as having men on surveillance for, so not going towards initial treatment. And actually, I think if we think about all the cancers that we find, it's even maybe a higher number than 80% that we're going in surveillance as our first shot.

We developed a protocol to think about two different scenarios. One scenario is the gentleman who's had a workup going into the HoLEP. So, it's a person that we were very deliberate about things. They've assessed their prostate cancer risk. We've determined that there's no cancer that's going to be present. They go to the HoLEP and then we find some incidental cancer. And then, the other one was in a setting where we didn't have the ability to do that for multiple different reasons. Maybe we had more urgency around getting them to the operating room for the HoLEP, and we didn't do that complete assessment.

Now, most people fall into the first category. And the idea there is if we have done an MRI already beforehand, before an elevated PSA say, and assess their prostate completely that way or if they've had lab values that suggest that there's no risk of prostate cancer, and we've cleared them just like we would anyone in the general population from the idea that they might have significant prostate cancer and now they're diagnosed with a small amount of low-grade disease at HoLEP, that person is different than someone that we biopsied for cause and, on a biopsy, a needle biopsy, which is looking at much less prostate cancer tissue, we're finding some incidental prostate cancer.

The guy who has it at HoLEP, and let's say their stage which in doctor speak is like T1a, they have less than 5% of their HoLEP tissue involved by cancer and they have low-grade disease, and that's the majority of our guys, that individual may be able to have slightly looser monitoring on their surveillance than someone who, say, came off the streets for prostate cancer screening, had an elevated PSA and then underwent a biopsy for that reason, and was found to have low-grade cancer, meaning that that individual, we want to follow them every six months with PSA, do a rectal exam every year. But we may think about future evaluation of that man's prostate only for cause. So for example, if the PSA was over 1 nanogram per milliliter after HoLEP, if the PSA velocity was increasing or how much PSA was being made per gram of tissue was high, that might lead us for more evaluation, which might be MRI and then a biopsy.

If we found more cancer than we thought, or a higher grade cancer, we put those people into a different category, one where we want to see where are we at six months in, what's their PSA doing, how do things look. And we're always going to do a confirmatory biopsy at one year, if they have, say, over 5% of their HoLEP specimen had low-grade disease, or if we found a little bit of favorable intermediate risk disease, and they would be following a more traditional surveillance protocol as we would do for men that did not have HoLEP. So again, it's kind of wordy, but the big difference is Dr. Krambeck and myself are recognizing that we're going to find more of these incidental cancers. And there's some cancers that are incidental and inconsequential, and we do not want to necessarily put that person through their paces and have them do a lot of invasive testing down the road. But we can't have a forget-about-it approach, we want a light-touch approach. And for people that are having incidental cancers that might develop into clinically significant cancers, we want to follow them a little bit more stringently, usually with confirmatory biopsy and often with confirmatory imaging as well.

Melanie Cole (Host): Thank you so much, Dr. Ross. You made some great points. Now, Dr. Krambeck, are there options for curative treatment that should be applied, that light-touch approach, depending on what you find? Tell us a little bit about what happens next.

Dr Amy Krambeck: Yes. So, like I had stated previously, the very first thing I want to do is ensure that this individual does not have prostate cancer that's contributing to their voiding symptoms. If they have prostate cancer contributing to their voiding symptoms, they really don't need a HoLEP. They need to see a urologic oncologist and have the prostate cancer treated. So, treating it before HoLEP is obviously ideal.

If for some reason the workup is negative or we somehow do not diagnose prostate cancer before and we identify a higher grade cancer in their specimen, those patients can still go on to an active treatment after their HoLEP. It's just a little bit more difficult. So, they are candidates for radical prostatectomy, but it is more challenging for the surgeon and would require more time and more reconstruction. But they can have a good outcome. They can get radiation, hormone therapy. Anything that you would offer before HoLEP can be offered afterwards. It just requires a more thoughtful approach.

Once you've gone in and operated on the prostate, it's more difficult to do more therapeutic interventions on that prostate, because they're at higher risk of urinary incontinence, scar tissue formation and erectile dysfunction. So, the best measure is to diagnose before. However, if you do diagnose prostate cancer that requires intervention afterwards, it's not impossible. It's just requires a more thoughtful, more directed approach after the HoLEP.

Melanie Cole (Host): I'd love to give you each a chance for a final thought. And Dr. Krambeck, starting with you, what research are you doing in this area? Give us a little blueprint for where you see this going as HoLEP becomes really the go-to therapy for BPH. What do you see happening next in the future?

Dr Amy Krambeck: It's such an exciting time for HoLEP. It's been around since 1998, but it's just now really taking hold as a top-tier treatment option for men with BPH. And as we have more and more individuals doing the procedure, we're finding out subtle nuances. We can increase the safety by changing the laser technology so that we have less bleeding. We're improving the morcellators so that they're less dangerous to the bladder. And hopefully, one day we can actually develop a standardized treatment assessment protocol so that we can catch men with prostate cancer before they undergo treatment and avoid a BPH surgery that they do not need. So, my goal is to develop a standardized diagnostic treatment approach towards HoLEP that any individual who does the procedure can use to maximize the patient's time, minimize testing, but still keep it safe and avoid unnecessary surgery.

Melanie Cole (Host): What an excellent goal that is. And Dr. Ross, last word to you. What would you like the key takeaways to be for other providers from this episode?

Dr Ashley Ross: I think of a few things. One, just to reiterate that HoLEP is really the gold standard in bladder outlet procedures to help men who have urinary symptoms relieve them. With that, we're going to find many incidental cancers and the majority of them will be low-grade and not require treatment and rather, he can just have surveillance. We're working on protocols and we have an eye towards dissemination of those protocols, Dr. Krambeck and myself, that will help people have sort of like a cookbook of how they can follow men safely and minimize additional testing. And I think that the other area of research that we're looking at together is doing things that can help understand disease risk after HoLEP. So, for example, we're looking at ways that the pathologists can use to find these small cancers and recognize that they're there or not. We're looking at different genomic assessments on those cancers as well.

Finally, for the patients out there, because just like Dr. Krambeck was saying, HoLEP is becoming more mainstream, it's important for them to know about it, to know that it's a very good option for their enlarged prostate and to understand that they not only can usually be relieved of their symptoms. But if cancer is found and it can't be watched, they're not burning any bridge. They have every treatment option that they would need.

Melanie Cole (Host): Thank you both so much for joining us. What an interesting topic today. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole.