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BackTable / Urology / Podcast / Transcript #16
Podcast Transcript: Management of Localized Prostate Cancer
with Dr. Jeff Cadeddu
We talk with Dr. Jeff Cadeddu about workup and treatment options for patients with localized prostate cancer. You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Focused History and Workup for Prostate Cancer
(2) Surgery vs. Radiation for Prostate Cancer
(3) Risk Stratification of Prostate Cancer Patients
(4) Active Surveillance of Prostate Cancer
(5) Management of Intermediate and High Risk Prostate Cancer Patients
(6) Incontinence and Impotence Risks with Prostate Cancer Surgery
(7) Adjuvant Therapy for Prostate Cancer
(8) Future of Prostate Cancer Surgery
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[Dr. Aditya Bagrodia]
Hello, everyone and welcome back to the BackTable Urology Podcast, your source for all things urology. You can find all previous episodes of our podcast on iTunes, Spotify, and at backtable.com. This is Aditya Bagrodia, your host this week, and I'm very excited to introduce our guest today, Jeff Cadeddu from UT Southwestern. Jeff is a professor of urology. He's been a pioneer and thought leader in kidney cancer and prostate cancer for almost 20 years now.
Personally, he was my first mentor into urology. So I'm very, very grateful for that. He's an excellent clinician. Excellent physician and surgeon. We're really thrilled to have him. Jeff, how's it going this afternoon?
[Dr. Jeff Cadeddu]
Great, Aditya. Thank you. And thanks for the introduction. Happy to be with you.
[Dr. Aditya Bagrodia]
All right. Great. So we're talking about localized prostate cancer. Of course, a lot to unpack. So we'll go ahead and jump on into it. To keep it focused, We're really going to just focus on folks that already have a diagnosis of prostate cancer. PSA screening of course is an entirely different discussion. So maybe we just start this out, Jeff, whether you're getting referred a patient or even newly diagnosed somebody with prostate cancer. Just one-on-one, can you walk us through your focused history?
(1) Focused History and Workup for Prostate Cancer
[Dr. Jeff Cadeddu]
Sure. So the evaluation of a patient diagnosed already comes in. Obviously, it was triggered either by a rectal examination or a PSA. So we want to get that history. We do want to focus in terms of targeted neurologic history. You want to get an idea of their lower urinary tract symptoms. You want to find out about their erectile function and whether that is with validated questionnaires in clinical practice.
Certainly, either way you want to get that history particularly. The whole point of getting the PSA, getting the rectal examination, having the pathology report available of course would be to risk stratify the patient, hopefully at that first appointment.
[Dr. Aditya Bagrodia]
Got it. Family history and underlying genetics.
[Dr. Jeff Cadeddu]
Of course.
[Dr. Aditya Bagrodia]
Predisposition syndromes are becoming more and more of a thing that we're attuned to. Can you tell us a little bit about the questions that you're asking?
[Dr. Jeff Cadeddu]
Oh, certainly. You do want to know their social history, of course. You want to know their past medical history, social history, and then past medical history. Their diabetes status. You want to know their overall cardiac health and comorbidities, of course. Because comorbidities will drive a lot of discussion in terms of management, whether it be surveillance, surgery, radiation, and so forth. Comorbidities play a big role.
And then of course family history. You're absolutely right. A family history of prostate cancer, breast cancer, pancreatic cancer. We definitely want to focus on whether or not there's risk. Patient age of course is also an important factor in terms of getting the history.
[Dr. Aditya Bagrodia]
And do you actually do a rectal exam on everybody that either you're seeing for an elevated PSA? I would think yes, but who carries a new diagnosis of prostate cancer?
[Dr. Jeff Cadeddu]
So the answer is a little bit nuanced. Yes, of course with elevated PSA, I do rectal examination. If the patient is already coming in and has a diagnosis, frankly, if another urologist has done the exam, I'm okay with understanding that particularly in the age of MRI, right? I think the sensitivity of an MRI towards the question of extracapsular extension is how I would worry about a rectal examination.
So I think if they had an MRI, I don't do a DRE on presentation. If they haven't had an MRI, I'll do the DRE. And I think as you do, probably most people would now get an MRI prior to initiating any local therapy.
[Dr. Aditya Bagrodia]
Yeah, absolutely. I would say that every one of my patients as a part of their evaluation and management gets an MRI. And is that the same for you as well?
[Dr. Jeff Cadeddu]
Yes. The pendulum is shifting so quickly, but I would say in 2021, any patient who's going to get local definitive therapy, whether it be radiation or surgery, I think the standard of care is rapidly becoming an MRI.
[Dr. Aditya Bagrodia]
I totally agree. And I would maybe even extend it to say, if you're considering surveillance, you really want to have a good lay of the land. How long after the biopsy, if they haven't had an MRI, do you like to wait?
[Dr. Jeff Cadeddu]
It's six weeks I would like to wait. I mean, I know our colleagues in radiology will wait at least 30 days, but at 30 days, a lot of patients are still expressing hematospermia. You know there's bruising of that prostate after the biopsy.
So I like to wait six weeks, eight weeks. Again, obviously depending on this clinical stage or the grade of the tumor. But if the typical grade group two, grade group three patient, I'd like to wait about six weeks for it to calm down.
(2) Surgery vs. Radiation for Prostate Cancer
[Dr. Aditya Bagrodia]
We're obviously going to talk about management and surgery here extensively, what if you find a hernia on your exam? Is that something that you're typically going to fix yourself if they come to surgery or do you coordinate with your general surgery colleagues?
[Dr. Jeff Cadeddu]
Yeah. Good question. So to be completely frank, I don't always check for a hernia on an exam. If the patient already comes in with a diagnosis, MRI, everything, I'll ask if they've had any symptoms, but a lot of hernias are generally discovered, incidentally intraoperatively, I would say, and I am comfortable managing those hernias myself intraoperatively. So I do not consult general surgery. I think if the patient had clearly a massive hernia bowel in the scrotum, first of all, the MRI would have picked that up. Second of all, then I would probably get general surgery involved. But a typical direct small hernia. I think it's hard to pick up on an exam and if it's clinically significant at time of surgery, I would repair it myself.
[Dr. Aditya Bagrodia]
Got it, got it. And if the patient's considering surgery, take a look at their abdomen. Are there surgical contraindications in your hands, extensive previous surgeries, X labs for accidents, colectomies, APRs? In your 20 plus years of doing this, do you feel like you can negotiate most of those scenarios?
[Dr. Jeff Cadeddu]
In terms of past history, right? What you're hinting at is of course every patient fills out a past surgical history and you'll focus on that at the time of the evaluation. Anterior to posterior, I don't find any anterior surgeries being a concern, prior mesh hernia repair, prior appendicectomy, colectomy. I don't think any of the... Even a midline hernia repair with mesh, those just increase the difficulty of the access. I do think that if the patient had an APR, I think that would be quite bit of a challenge in terms of the risk of rectal injury. I've actually personally stayed away from those cases.
We'll get to it eventually, but unlike as you know, and some of the people in the audience know, I do a lot of kidney cancer. Unlike renal cell carcinoma, I don't think we should ever be in the business of forcing surgery into a scenario that is anatomically not favorable because there is a viable, alternative, and very efficacious alternative being radiation, one of the forms of radiation therapy.
For any surgeon, their comfort level with the anatomy with the prior surgical history is important. And if they're not comfortable with that, no one, me or you can be dogmatic about what to do and when to do it. I think a frank discussion with the patient, regardless of age, regardless of grade is that if you're not comfortable with this anatomy to have the patient reconsider a completely efficacious treatment being radiation therapy. I don't know if that answers your question.
[Dr. Aditya Bagrodia]
It does. It does. In that vein, do you have everybody that has a prostate cancer and a life expectancy that merits treatment see our colleagues in radiation oncology, or do you have that initial discussion with them?
[Dr. Jeff Cadeddu]
I definitely have the initial discussion with them and I fairly spend a fair amount of time discussing the advantages of radiation therapy, the risk of radiation therapy and offer every patient an appointment with radiation oncology.
It may be the scope of my practice, but most patients have already...by the time they come to see me have already decided to do a surgery. But if it's a newly diagnosed patient, I do offer it to everybody, and if I diagnosed it, I would say many patients do take that offer of consulting with the radiation oncologist. It's imperative that we offer the patient that. I don't think it's imperative that we mandate that consultation.
[Dr. Aditya Bagrodia]
Yeah. I certainly see a handful of patients that come in and their mind is made up on surgery or maybe a referring surgeon has told them that they need surgery, take a close look at their pathology and they've got some Gleason score three plus four equals seven and just a few cores, small component pattern four. Let's take a step back here and maybe considering surveillance.
I think I wholeheartedly agree that it's incumbent on us to really run through the whole gamut of options. You ever find yourself talking patients out of surgery or out of treatment altogether?
[Dr. Jeff Cadeddu]
Oh, certainly. I mean, the common one is patients who present with low or very low risk prostate cancer who were already advised that they should have surgery. I find myself counseling those patients and vigorously, aggressively trying to steer them towards surveillance.
Yeah, I think that's a low-hanging fruit. There are patients who come in, as we discussed already with hostile abdomen over hostile pelvis for whatever other procedure they've had three TURPs already. They're diabetic. You're worried about them being incontinent. Those patients, even though they may have come to see me with their heart set on surgery. I will spend an extra effort trying to counsel them on the long-term efficacy of radiation as a viable alternative. For sure.
[Dr. Aditya Bagrodia]
And what about when you get the... All right. You've talked to us about radiation. You've spent some time talking to us about surgery and they say, "Well, doc, you're the expert here? What would you do?
[Dr. Jeff Cadeddu]
Well, I always answer that question as that I'm 54 years old. So what I decide at 54 it may not be appropriate for where you decide at 65, 72. So I do try to steer that conversation away from that. But if the patient is 54, then I would say that, "Look, what I usually tell people is this, the majority of patients who would benefit from local therapy under the age of 60, the majority of those patients, I will be fair to say, 80 to 90% of those patients choose surgery. And the vast majority of patients over the age of 70, I think when counseled appropriately will choose a radiation therapy as an efficacious treatment.
So the people in their 60s I think have the hardest decision in terms of what is best for them. And this is basically a math question. It's a question of life expectancy. We know from many trials that the efficacy of treatment after the age of 65 is very questionable as it is, period. So I tried to steer patients, certainly in the late 60s and 70s. I don't encourage them aggressively to do surgery. I do encourage them to strongly consider radiation.
[Dr. Aditya Bagrodia]
Yeah, certainly a scenario that I find not infrequently is really across the age spectrum, but particularly in young patients, this fear of recurrence. Maybe not very aggressive cancer. And they like the idea of having radiation as an insurance policy, as a secondary option in their back pocket. How do you guide them through that process? Here, we're talking a little bit about adjuvant or salvage radiation versus salvage prostatectomy. Somebody told them that, "Well, if you get radiation and your cancer comes back, it's going to be a tough go at it."
[Dr. Jeff Cadeddu]
So I try to tell all patients and this depends, again, at the age of presentation, but I try to counsel patients in this following scenario. That is there is no trial that I am aware of where the disease free survival is different. That is the disease free survival at 10 years, between surgery and radiation in one of the formats is comparable. It's not 100%, of course in either scenario, but it's comparable.
So the fear of recurrence is legitimate, but it's no different in surgery or with radiation. And I tell patients that this is where the age comes in. So if they're presenting with initial diagnosis at 70 years old, and they have a recurrence, they're likely to have a recurrence at more advanced age, and any recurrence likely can be managed either conservatively with systemic therapy eventually such that the fact is that they will likely die of other causes before they would die of prostate cancer.
We know that. What you're hinting at is it's much more important for a man in his 50s and early 60s, because if they have a recurrence at 10 years, or they have a recurrence at five years, now they have to do the math. And yes, in that scenario, the one advantage of surgery is that it allows for a salvage modality that has low morbidity. Conversely surgery, radiation, if there's a salvage scenario that's necessary, the surgery morbidity is greater, right? Does that make sense?
(3) Risk Stratification of Prostate Cancer Patients
[Dr. Aditya Bagrodia]
Absolutely. So when you're sitting down with the patients and they're coming in with grade group three Gleason score of four plus equals seven prostate cancer, PSA's of 10, are you actually using any type of preoperative, predictive models, part in tables MSKCC nomograms or giving them more risk stratified, broader ranges?
[Dr. Jeff Cadeddu]
I don't do that in clinical practice. In my practice, at least it takes a little bit too much time. I also find that giving or providing data regarding nomograms to patients, the average patient, at least in Texas comes back to what you said, which is, "Doc, what would you do?" Right? So I don't find doing that. I do risk stratify everybody per AUA and NCCN guidelines, and then provide them with that information. And that the favorable and unfavorable intermediate risk, if they have a 10-year life expectancy, they would benefit from treatment at least in preventing metastasis. And if they have a long enough life expectancy would probably benefit from, in terms of dying of prostate cancer.
The high risk patient, I think, as long as they have a life expectancy of five to eight years probably would benefit from treatment. And I just kind of ballpark it for the patients. I think patients like that going into... This is the rare patient who can understand the nuances of some of those nomograms.
[Dr. Aditya Bagrodia]
Yeah. I wholeheartedly agree. I think you have to read the room a little bit and see what's going to be a digestible format for the patient. Life expectancy prediction is tricky business. We've all seen patients that are 50 that look like they're 80 and vice versa. You mentioned five years as a landmark that pops up in the AUA guidelines, 10 years. How do you assess functional status life expectancy?
[Dr. Jeff Cadeddu]
I don't assess it. Again, in the real world, I think community urologists would appreciate the fact that we don't have time to sit around and input patient data into some sort of calculator. You also realize that no patient likes to be told that they're 65 years old. There's no chance in hell they're going to live to 75. So it's nuanced. You talk to the patient and then when you do talk to the cardiologist, which is most of their comorbidities, no cardiologists will stick their head out and say, "Oh, yeah. This patient definitely will be dead in eight years."
Everything's pretty nuanced. Like you said, you have to feel the room, get a jist for the patient's health. If you've got a history and the patient is 70 years old and has diabetes and hypertension and coronary artery disease, I think you have to have a discussion where, okay, well, you might really not get the long term benefit of surgery.
I think that the greatest benefit of surgery is a really long-term. That's 15-year disease free survival. So those patients, it's a pretty easy conversation. Also, it's hard to find it's a 55-year-old who similarly doesn't think they're going to live to 65. So I don't calculate anything, but you can have a co-morbidity discussion with the patient and weigh the benefits of radiation versus surgery.
And in the occasional patient, even active surveillance. But all the nomograms in the world, I think most people in a busy clinical practice will agree that there's still the art of medicine, the nuances of counseling patients and the gestalt of how they're doing. I think patients are honest with themselves and then we'll come to the realization of what may benefit them best.
[Dr. Aditya Bagrodia]
I wholeheartedly agree. I think it goes into, we're trying to convey a message. If I've got a patient that's 77 with a little bit of grade group two prostate cancer, and they want something done, that's the guy that I pull up the life expectancy calculator, put in their history of have you had a TIA, a stroke or is your blood pressure okay? Here's your cancer characteristics. And then this little box pops up. There's a hundred people and it says three men will be dead of prostate cancer. 80 are going to be dead of something else, and seven are going to be alive.
Then I have some ammo to go in and say, "Listen, my bar to help you is 3% and my bar to hurt you is fairly tremendous as soon as I walked through what surgery radiation looks like. Well, that's incredibly helpful. So maybe let's just start kind of jumping into some patients here. So very low risk or low risk disease. PSA is under 10. Relatively modest volumes, grade group one. Are these generally going to be surveillance patients in your practice?
[Dr. Jeff Cadeddu]
Yeah, they definitely are. I'm pretty dogmatic about that. Certainly, there are colleagues who would certainly consider a more aggressive treatment, but regardless of age of the patient and health of the patient, my first recommendation will always be active surveillance. If they have very low risk disease, I will be pretty blunt and I will tell the patient, "I will not treat you. If they want surgery, they have to find another urologist."
If they have low risk disease, that is Gleason 6, right? Three more. So let's say half a prostate. It's not nuanced. Let's say they have six out of 12 cores Gleason 6. Okay. They're young. We get an MRI, we can get an oncotype. We can evaluate further. There are some patients with low-risk disease that would benefit from a local therapy, but by and far in my practice, that's single digits, single percents of patients. I endorse aggressively active surveillance for low risk prostate cancer.
[Dr. Aditya Bagrodia]
Yeah. I think especially the younger folks spending a little bit of extra time is invaluable high volume group, grade group one Gleason 6, as you mentioned, perhaps has some people's attention a little bit more. You mentioned oncotype. Are you routinely using genomic classifiers in these scenarios? Other young guys, grade group, one high volume or low volume grade group two?
[Dr. Jeff Cadeddu]
Not routinely. So the low volume grade group two, a little bit advanced age. I will use it when they're similar to the scenarios that earlier where the patient wants treatment. And I think active surveillance may be reasonable. And if the score comes low, I think it reinforces that. And then conversely, the same thing. If I have a very young patient with significant volume of Gleason 6, those patients are usually more amenable to going ahead with treatment, but certainly I'll use it in that patient. So it's a nuance of, I probably would have the test less than 10% of my patients, but it is to help steer the discussion in where you think the patient may benefit.
[Dr. Aditya Bagrodia]
One thing that always stuck out to me, Jeff, that I recall learning as a resident from you is that you kind of preset the expectations, whether that's Prolaris, Oncotype, or decipher that here's the results. So talk us a little bit about that. Also, that was a very useful way to think about them.
[Dr. Jeff Cadeddu]
I use Oncotype and then in the pre diagnosis, I'll use 4K score a lot. And I tell the patients that comes back as a percent, right? A percent risk. We have to be comfortable. It's not a black and white test. This is not a pathology where you're going to come back with a cancer, no cancer. You're going to come back with a risk that you might have aggressive disease. And what is that risk that you're comfortable with? So you have to preset that.
You don't want a scenario, we get a result back and it says, "There's an 8% chance you have aggressive disease." And then the patient says, "Well, I don't know what that means. What is 8%? Is that high or is that low? So I try to always... before I order any of these tests, I will tell them, "Look, we have to predetermine our results? If it comes back low risk and that's 7%, are you comfortable knowing that there's a 7% chance we're missing something?"
Obviously, if it's 50%, you wouldn't. So is it 3%, you're okay, 10% you're okay. 50%. So I make the patient kind of decide in advance of ordering the test. And if they are indecisive of what is the number that that's going to scare them into treatment or no treatment, then I might not even know what to test. Is that what you're getting at, I think?
[Dr. Aditya Bagrodia]
Absolutely. Yeah. I think I walked through this with the exact same type of thing with my patients even once you have the information, whether it's a nomogram. I might say that one in a hundred chance of dying, no big deal, but we take insurance for a lot of things to mitigate less than 1% risk.
And then exactly like that, about 2% or 3% or 5%. I think having that line in the sand is useful. So let's just say patient comes in, low risk, very low risk, broad strokes, PSA's, MRI, repeat biopsies. Can you tell us what your practice is? Are you getting PSA's at six month intervals, annually? Do you get an early repeat biopsy? I assume everybody that can get an MRI gets one, if they haven't had one.
(4) Active Surveillance of Prostate Cancer
[Dr. Jeff Cadeddu]
Right. So everybody, if they haven't had an MRI, they definitely get an MRI once they come back to see me. Again, I think I do try to practice the guidelines in the sense that someone newly diagnosed with low-risk prostate cancer is just that they're diagnosed with it, but the first step before you would consider active surveillance is to have to go through a confirmation process.
So active surveillance for me, doesn't start until they undergo a confirmatory evaluation. And of course that means confirmatory biopsy for most patients. Only after that second confirmatory biopsy, would I then offer the patient with confidence active surveillance. So I make a very big distinction about that to my patients. So if they have systematic biopsies coming from the outside Gleason 6 and two cores, three cores, I will tell them, "Okay, let's wait about six to eight weeks. We'll get an MRI. If we see a lesion on the MRI, we'll get a PSA every six months and we'll probably repeat the biopsy somewhere between six and 12 months. Guidelines say 24 months."
And if that confirmatory biopsy is Gleason 6, then they embark on active surveillance. If they come in with an MRI already prior to the biopsy, high res three lesion or no lesion, someone did a biopsy anyway, and you have Gleason 6. Well, then I feel a little bit better, but I still would ask the patient to get a confirmatory biopsy within 12 to 24 months per guidelines.
So to me, there's a confirmatory window where they are leaning towards active surveillance, but they need to have that confirmation biopsy. Once they get that confirmation biopsy and it confirms Gleason 6, then my practice is PSA every six months. And if they have an MRI, probably I think that the pendulum is going where they'll probably have an MRI, at least in the beginning every year.
And if there's a change in the lesion, a biopsy, if there is a new lesion that wasn't there before biopsy, and then a follow-up biopsy, again, for guidelines is anywhere between two and five years after the confirmatory biopsy. So then it just depends on where the PSA or MRIs change. I think that's how most people are practicing now.
[Dr. Aditya Bagrodia]
Yeah. Very similar to me. Once they've had their confirmatory biopsies, PSA is every six months. At 18 months, they get an MRI. If that looks fine, continue on with PSA's at three years, repeat an MRI. And pretty much at that time, they're going to get a biopsy. All right. So let's say we've confirmed them to be low risk or very low risk and they're fairly symptomatic, significant LUTS. You've got an MRI. Maybe they've got a 60 gram prostate median lobe. How does that kind of factor into your decision-making?
[Dr. Jeff Cadeddu]
The cancer is not the cause of their LUTS, right? Of their medium lobe. So I think they should have that pathology treated. And obviously that is whether medical therapy doesn't work, whether or not they'd benefit from a TURP or some sort of surgical procedure for their BPH related symptoms. I personally don't think the risk benefit of radical prostatectomy to treat LUTS plus low risk prostate cancer is worth it.
I'm very conservative about it. I know there are surgeons that would say, well, with significant medically refractory LUTS, why not just take out the prostate at the same time? So you get rid of the Gleason 6. I think the morbidity of that is significantly greater than a TURP. And I don't think you should be treating LUTS with a radical prostatectomy. That prostate cancer, as we know, we just said, we'd never killed them. So they just should continue an active surveillance for the Gleason 6 and take care of their LUTS.
[Dr. Aditya Bagrodia]
Yeah, totally agree. I feel like it's one of those things that may be absolutely bringing a gun to a knife fight. How about if the patient is interested in ablation?
[Dr. Jeff Cadeddu]
Ablation in terms of focal therapy or whole gland, as a treatment for Gleason... Are you talking now, again, low risk or intermediate risk?
[Dr. Aditya Bagrodia]
This can be low-risk. We'll hop into intermediate risk here. Let's just say, it's a younger patient or a higher volume, and of course we could have a whole discussion on hemigland, whole gland, focal, but do you think it's going to obtain more of a role or whether it's justified or not be a patient-driven phenomenon?
[Dr. Jeff Cadeddu]
This is as much medically complicated and as politically complicated in terms of how to deal with focal therapy or ablation of the prostate. My feeling is that in the low risk patient who qualifies for active surveillance, I don't see any reason that that patient should to go any kind of treatment, whole bland, focal ablation, what have you. We have 15-year active surveillance protocols results for these patients where they didn't have any of these treatments and they're all alive and they're all fine.
So I don't know why you'd treat something that's not a threat. We don't treat other conditions that don't progress. I think if there's progression, then they should undergo the appropriate treatment for that progression. And I don't think they need to undergo focal therapy for something that's low risk.
[Dr. Aditya Bagrodia]
And what are those triggers for treatment in your practice?
[Dr. Jeff Cadeddu]
So rising PSA, right? So certainly we know that as soon as their PSA goes over 10, it's no longer low risk. So if the PSA is trending towards that, I think that's a concern, the PSA philosophy, right? We can have upgrading on subsequent biopsy, MRI biopsy. So my triggers would be either upgrading or upstaging either by MRI or PSA progression.
[Dr. Aditya Bagrodia]
Right. We're fortunate to have a really tremendous team offering MRI inboard biopsies, MRI ultrasound fusion biopsies. And let's say they've been five or six cores coming out of a single lesion that are all grade group six, patient is little nervous. How do you handle that, that situation?
[Dr. Jeff Cadeddu]
If you have a lesion in your biopsy 10 times, you'll have 10 of 10 cores, if it's all Gleason 6, right? The number of cores in targeted biopsies are done to increase the yield, but the number of cores themselves should not drive the decision-making. Right? So I would say if they have a five millimeter, PIRADS 3, PIRADS 4 lesion on MRI, and you have three out of three cores that are Gleason 6, it's probably reliable.
If it's a 17 millimeter lesion on MRI and you have three cores and three out of three are Gleason 6 may not be as reliable, right? So this is no different than kidney tumor biopsy now. So the number of cores, I think, is also relative to the size of the lesion. And I think that would influence how you counsel the patient.
[Dr. Aditya Bagrodia]
Got it. So maybe moving on to intermediate risk disease. We've decided that between the cancer characteristics, patient's comorbidities, something should be done. Can you walk us through your prostate cancer talk for those that are electing treatment?
(5) Management of Intermediate and High Risk Prostate Cancer Patients
[Dr. Jeff Cadeddu]
So in the patient that elects treatment, I feel that I try to be as balanced as possible. I don't think we can advocate for a patient that oncologically one treatment whether it be radiation or surgery is better than the other.
So if the patient, and I'm going to table a focal ablation and whole gland ablation. The guidelines still don't endorse that as first-line therapy. And I wouldn't endorse them as first-line therapy either, right? So it's either going to be IMRT, SBRT, Brachytherapy, proton if available versus radical prostatectomy, open or robotic. The way I counsel a patient is I tell them that both radiation and surgery are not risk-free.
And the only thing you can control between the choosing of them is what kind of risk and where do you want the risk? I say what kind of risk? Because obviously we're getting at the concepts of continence, potency and rectal side effects versus where do you want the risk? Do you want the risk upfront with surgery or do you want the risk delayed with radiation therapy.
Neither treatment is risk-free. I walk them through where do you want the risk? So obviously all the radiations, the most valuable thing about radiation therapy is that it's not surgery. There's no pain. There's no catheter. There's no bleeding. There's no anesthesia. There is no risk of incontinence practically speaking with radiation therapy in the modern era. Yes, there's some delayed risk of erectile dysfunction, but none of those surgical risks, none of those perioperative risks.
And that's the best thing about radiation therapy. You continue to go to work. There's no social downside too much in terms of socioeconomic impact from it. On the other hand, we know that there are irritative symptoms with higher risk disease. There might be the side effects of ADT involved. So you have to bring that into the conversation. So the short-term risk of radiation may involve some ADT related issues, of course.
But then the downside of radiation as you hit earlier is the delayed risk is that what if you have a recurrence and you're still young and you're still healthy? How do you do salvage therapy? So you're deferring risk, I think with radiation. With surgery, I tell the patient you're taking all the risk upfront. You're taking this risk of surgery. You're taking the side effects of pain and catheter and risk of bleeding and the recovery and the risk of incontinence, at least temporarily, the risk of erectile dysfunction, hopefully only temporarily.
But with organ confined disease at the outcome, you'd probably have a little bit more security long-term that if you do have a recurrence salvage radiation, we know the morbidity is pretty low. So you have the long-term security of at least oncologically somewhat a little bit more confidence in the outcome.
So I counsel my patients every day when I talk about radiation and surgery about where and what kind of risks do you want? I try not to tell them what to do. I try to steer them to understand that, that nothing is risk-free.
[Dr. Aditya Bagrodia]
Yeah. I think that sounds like a pretty balanced conversation. You mentioned organ confined disease, and of course the decision of surgery and radiation persists is relevant to high-risk disease. A little bit about staging. CT scans. Do you ever get CT scans on patients?
[Dr. Jeff Cadeddu]
Again, of course, with the high risk patient. With the favorable, intermediate, generally, no. Almost never. And then unfavorable intermediate, they all would get MRIs now. Right? So if they have an MRI, there's a question next to extracapsular extension, T3b disease, seminal vesicle involvement, I mean, all of a sudden now you're locally advanced. Yes. I get a CAT scan and a bone scan, but in the age of MRI, you also get a good look at the pelvic nodes. So the real advantage of CT would be higher common iliac nodes and retroperitoneal nodes.
Well, those patients generally have a PSA above 10. They generally have probably more likely to have concerning imaging pathology, concerning MRI in terms of extracapsular disease or whatever. So not that many patients in the immediate get MRI, get a CAT scan, unless there's some other concern. Does that make sense?
[Dr. Aditya Bagrodia]
Yeah. I mean, I would say that in my practice, if their MRI doesn't show any concerning pelvic lymphadenopathy I’ve essentially stopped getting CAT scans of the abdomen. I mean, if their PSA's in the 30, 40, 50 range then I'll actually get their chest image as well along with the bone scan. High-risk disease, low PSA, are those patients getting bone scans?
[Dr. Jeff Cadeddu]
Yes. In my practice, yes.
[Dr. Aditya Bagrodia]
Okay.
[Dr. Jeff Cadeddu]
We know in high risk disease that the D differentiated malignancy does not make PSA per volume. As you know, you'll see patients with Gleason 8, Gleason 9 particularly. So grade group five disease who have a PSA of four or three, and they have extracapsular disease in their MRI. Right? So I don't think PSA with high grade disease is a reliable indicator. So those patients, I think I always give a metastatic evaluation.
[Dr. Aditya Bagrodia]
I think that makes sense. Absolutely. Are you surveying many patients with grade group two disease?
[Dr. Jeff Cadeddu]
Not many. I would say patients often are usually in their 70s or have comorbidities in their 60s and a grade group two, not grade group three in general. But I do. I usually will get an Oncotype in that patient. And if it shows them to be low or intermediate, then I think it's reasonable to follow those patients. I counsel them. They know that over the 10 years they may develop... Well, not watchful waiting. So if they have progression, we would try to initiate treatment. But there's a risk of metastatic progression as we know.
[Dr. Aditya Bagrodia]
Yeah. And does the percent pattern four play into that conversation? So let's say there are 50% core involvement, 90% grade pattern three, 10% pattern four.
[Dr. Jeff Cadeddu]
That's the favorable and immediate patient. Right? So I think in an older age, that surveillance makes a lot of sense for those patients as opposed to the grade group three. If it's 60, 70% pattern four, no.
[Dr. Aditya Bagrodia]
Right, right. I mean, even further into the weeds, oftentimes it's a single core of grade group two. And in that core you have 5% pattern four, and I'll often try to talk patients off the ledge in that scenario.
[Dr. Jeff Cadeddu]
Well, and that's also a scenario where a confirmatory biopsy is going to be critical, right? So they need an MRI. They need to go through a confirmatory biopsy. And if your confirmatory biopsy still shows low volume pattern four, I think you'll feel a lot more confident. Again, no one goes into active surveillance until they finished the second biopsy. So this the confirmatory biopsy.
I can't give someone advice to do active surveillance. They just entered this limbo period until they get the MRI 12 months later, six months later. Again, another biopsy.
[Dr. Aditya Bagrodia]
Totally makes sense. And you kind of touched on this earlier, when you talked about radiation and clearly, the way that radiation can be delivered is extensive breaking therapy, combination therapy with or without ADT, SBRT and so forth. If you're starting hormones, do you start them on vitamin D and calcium or get your endocrinology colleagues involved in early?
[Dr. Jeff Cadeddu]
Yes. The answer is yes. If they go short-term ADT six months for an unfavorable, intermediate risk disease, and they get six months of ADT, yeah, they should get a calcium and vitamin D. I don't get endocrinology involved in that patient. And I don't really know if six months of vitamin D and calcium, when the patient should recover, it's going to make that big of a deal. But high risk patients, they're going to go for two years, likely two years of ADT. They should be aggressively managed.
[Dr. Aditya Bagrodia]
What about going back to prostate anatomy, larger lobes, median lobes, is that going to be a relative contraindication to radiation in your practice?
[Dr. Jeff Cadeddu]
That's an example where you think that surgery might offer the patient better outcomes in terms of the urinary symptoms.I think that's where you're getting at. But I would not counsel that patient without them actually seeing and visiting with a radiation oncologist and having the radiation oncologists counsel and address that with the patient as well. So if that makes sense. Especially, if the patient, if they're going to get ADT with their radiation therapy, I just want to have a more nuanced discussion with the radiation oncologist who often are pretty straightforward with the patient.
They'll tell the patient in our institution, as you know, that surgery may be a better option for them because of a hundred grand with a median lobe.
[Dr. Aditya Bagrodia]
Yeah. I think it's fair. I mean, certainly if they're getting ADT, you maybe have a little bit of a run end and you get some shrinkage. You have some improvement in symptoms, but I would agree that their reflexive 50 grams or larger is automatic surgery is probably of historical interest and non-data driven.
[Dr. Jeff Cadeddu]
Yeah.
(6) Incontinence and Impotence Risks with Prostate Cancer Surgery
[Dr. Aditya Bagrodia]
So kind of getting a little bit into the nuts and bolts of it, urinary symptoms wise, what do you tell the patients if they're electing for... Let's just leave it at radiation, again, comes in so many flavors with various iterations that that conversation needs to be comprehensively had with the radiation oncologist just like surgery with us. But in terms of urinary symptoms, can you tell us a little bit about what you tell the patients that they can expect over the days, weeks and months following surgery?
[Dr. Jeff Cadeddu]
I think the practice now is that most people get if they do surgery, they do it robotically. So the anastomosis is so well visualized that most of us just leave a catheter in for some five to seven days. So I tell a patient once the catheter comes out in my practice about 40% or more of the patients will have zero to minimal leakage for a few days, and then they do well.
What I try to do in fact is tell the patients that you can count on that. So what you want to do is focus on more of the intermediate term. So I counsel patients that, "Look, you're going to probably have some degree of stress incontinence for a couple of weeks, couple of months." In experienced hands, probably 95% of patients regardless of age are going to regain social continence by six months.
I think that's pretty fair. So I don't want to over promise them that they're going to have instant continence, though some do. And I try to prepare them that usually within three to four months that continence will recover, and there's a few guys who struggle at six months. But I think one of the biggest important things to tell people is that any incontinence that goes beyond six months is correctable, in my opinion.
The biggest knock on surgery, the biggest criticism and fear of the patients is that they're going to be incontinent for life. And as you know, that's incredibly unlikely, incredibly rare. It is also unfortunately incredibly common that the average urologist who does radical prostatectomy, including myself, do not know how to surgically correct stress incontinence in a male.
So having a partner, which we're fortunate to have, who can correct this, whether it be a male urethral sling, and in the rare occasion, patient with an artificial sphincter, I tell patients, "Look, surgery, you have a short-term risk of incontinence, but the only reason you're going to be in a diaper the rest of your life is if you choose to do so.
And any friend of yours who had surgery that is incontinent, and that's why you don't want to have surgery because your friend Joe has been incontinent for three years, Joe was never given the appropriate medical advice to seek surgical correction of his incontinence. I don't see any reason that man after radical prostatectomy should be incontinent beyond six to nine months.
And that's where the patients have misconceptions. I think that's an important point. Patients come in to see us so afraid of surgery because they think they're going to be a diaper forever. And that is farthest from the truth in the 21st century.
[Dr. Aditya Bagrodia]
Yeah, I agree. I run through the statistics and so forth and my personal statistics, of course, and then I'll tell them off the record, you should be dry ultimately.
[Dr. Jeff Cadeddu]
Right.
[Dr. Aditya Bagrodia]
With that being said, when it comes to the kind of erectile aspects of the talk of the prostate cancer surgery talk, I will not go off the record and say, "Off the record, you should be potent." I think that's a little harder to guarantee if you will. Before we move into to the erectile aspect of it, so I typically have my patients do cables for about a week, 10 days prior. And if they're really struggling with incontinence, either small volume, that's bothersome or larger volume, which I've found it impossible to predict to that patient's going to be, I'll get them in to see a pelvic floor physical therapy, generally wait to see how they do in a six to eight weeks out. But if they're really having a hard time, just have them see our colleagues who are actually tremendous and can add to that.
[Dr. Jeff Cadeddu]
No, I think that's a really good point that I don't know how widely available it is in the community, but we do benefit at the university setting of having pelvic floor physical therapy. And I will do the same. I usually see my patients back somewhere between eight and 12 weeks after surgery. And if they are still struggling with continence at that point, and it's significant, if you can say, "Oh, they're getting better every day," you can predict that this is mild. One pad a day. I don't think you can do anything.
But otherwise, I will then send them to PT because I don't think we should intervene surgically on these patients until they're well beyond six months to maybe nine months. So they still have a window of time. And I think the physical floor therapy is something that people in the audience should inquire about for their patients, because it does help. It's not dramatic, but we do see patient reported improvement with that kind of teaching.
[Dr. Aditya Bagrodia]
Okay. So I think we've got a really nice flavor for the incontinence aspect of it. Erections wise, how does that conversation go? And maybe I'll start out with, if they've got an MRI with some concern for prosthetic extension, are you framing this as a likely going to be a unilateral nerve sparing, or is that an intraoperative decision for you? I mean, of course there's shades of gray.
[Dr. Jeff Cadeddu]
Acknowledging that there's shades of gray and there's variable extent of extracapsular extension. I don't think MRI is the most reliable predictor unless it's gross extracapsular extension. So I always in my practice leave it to an intraoperative decision. I think as one gets experienced, one can feel more confident doing that. So I'm not against empiric counseling of unilateral nerve sparing, but I think as one develops more and more experience and confidence and follows their outcomes, looks at what they did versus what the pathologic outcome was, I think you can nuance this. They got an intraoperative decision.
There really is partial nerve sparing. Again, with more experience, you can do that. So I try to tell patients that we will decide intraoperatively to answer your question. And I feel strongly about that. I personally, at this point in my career, don't believe that empiric preoperative decision-making on unilateral nerve sparing should be done unless the MRI clearly shows T3 disease.
[Dr. Aditya Bagrodia]
Can you give us a little bit of your counseling on timeline and statistics for recovery of potency?
[Dr. Jeff Cadeddu]
I'll tell patients all the time the following. The recovery of your potency depends upon the volume of disease and stage, depends on your preoperative performance status. I'm never going to make you better. It depends on your age. The younger guys take a licking and keep on ticking a lot easier than the older guy.
And then the last factor is depends on your surgeon. So I can't control their preoperative status. I can't control their age. I can not control the volume of disease. So there is value in counseling a patient when they're younger, back to the active surveillance in grade group two disease. Do you do active surveillance? Well, if you're young and if you're low volume, it's more likely I'm going to have a better outcome.
Then age, right? So the 40 year olds, 50, 40 year or decade to 50 decade to 60 decade to 70 decade, patients just incrementally do worse with every decade of life in all of the studies that have been done. So I try to nuance all that in. Unlike continence where I think almost no matter what age, 95% of those patients are going to be continent. It could be a week or six months.
Potency really is nuanced. So then you want to ask me, you have to give me a scenario. Is it a 55 year old low volume disease, perfect erections, is going to do, 80, 90%? And if you're 70 years old with high volume disease and preoperative PD, five inhibitors and 100 milligram dose of Viagra because it's already struggling, well, you know that guy is not going to be potent, no matter how good you think you are of a surgeon.
So it's a much more nuanced discussion. But I also tell the patients that just like continence, what you lose is erectile function, right? A whole lot of patients have a misconception that they'll never have sex again. A lot of patients have a misconception that they never have sensory function again. There are a plethora of technologies and needs to get erectile function restored, and we will start that immediately after surgery.
I think if you counsel patients that way and you really make sure they understand what the consequences are, I think they are much more accepting of that risk and knowing that they can regain function, particularly if they're in a stable relationship, their partner would be supportive.
[Dr. Aditya Bagrodia]
I kind of tell all my patients, it's a weird thing to wrap your brain around, but you can actually have an orgasm without having an erection and without having an ejaculation. And usually there's some kind of shock and disbelief that follows. And I wholeheartedly agree. Obviously, we work in the same practice. We've got a really nice support, but starting in with low dose phosphodiesterase inhibitors and ramping up based on prioritization, based on function with erection devices, injections, and ultimately if they do require surgical therapy, we've got people that do that routinely and are very, very good.
Jeff is an excellent surgeon. I feel super fortunate to have trained with him. There's so much we could cover in terms of lymph node dissection, continence maintenance techniques, but I think we're going to be kind of outside of the scope. So you mentioned [inaudible 00:51:05] 12 weeks. That's where you get your first PSA kind of get a lay of the land. We talked a little bit about pelvic floor physical therapy, when to incorporate.
Let's say the pathology comes back fairly aggressive. PSA is fortunately undetectable. Are there patients that you send for true adjuvant radiotherapy?
(7) Adjuvant Therapy for Prostate Cancer
[Dr. Jeff Cadeddu]
Yes. There are patients I send for these, the consultation that I do reflexively. And I won't be paternalistic and not offer it to the patient. So what I'm getting at is some people would say, "Oh, we should always wait. You do not send them to radiation oncology,” but I do. Anybody with a node positive disease, I send for consultation with medical oncology and radiation oncology.
So then outside of that group, if they have high risk cancer, it's T3 and they have a positive margin, I send those patients for consultation with radiation oncology. I think those patients are at high risk. If their nodes were negative and they had T3 disease, I may have missed a node and they actually obviously have a risk for early local recurrence.
If they have high risk disease or a grade group three disease is T3A, but negative margins, I often will not send that patient for radiation consultation I think if they have negative margins. Any patient that has a positive margin and T2 disease, I usually will watch it because I think some of those for sure we know are going to be iatrogenic and not real T2 positive margins.
I feel confident enough at this point in my career that I probably didn't leave any real prostate behind, if they have a positive margin T2. So those patients I usually watch. So I think that kind of covers the group that the scenarios where we would consider radiation positive margin T3 disease N1 disease. N1, yes. T3 with positive margin, yes. T3 with negative margin, probably not. T2 with a positive margin, probably not.
[Dr. Aditya Bagrodia]
Totally. For the high risk patients, are you prepping for these possible scenarios on the front end pre-surgical counseling?
[Dr. Jeff Cadeddu]
Absolutely. When I see a high risk prostate cancer patient, I tell them that this is not your unimodality cancer. You have to be thinking about this as multimodal therapy like we do with other cancer. And if we do surgery first, you have to be mentally prepared for having adjuvant to salvage radiation therapy. And if it's N positive disease, probably systemic therapy for some period of time as well. So I prepare them all that anybody with high risk or T3 disease, it could be intermediate risk, but they have T3 and MRI. I will tell them that we are going into this as multimodal therapy.
(8) Future of Prostate Cancer Surgery
[Dr. Aditya Bagrodia]
Yeah. I think that's absolutely mandatory for managing expectations. And you know, of course, if you do this, you're going to see persistently positive PSAs or PSA recurrences. And just to kind of keep the floor from falling out of our patient's legs, letting them know that that's a possibility's mandatory. So I think we've covered the gamut of it.
Of course, we could talk about localized prostate cancer until the cows come home. Over the course of your career in kidney and in prostate, you've seen less and less invasive options. Do you think for prostate cancer, with earlier tools like MRI for screening, ablations, minimally invasive prostatectomy is prostatectomy going to be like the CABG to cardiac stents? Is that kind of an analogy for us? Is that what's coming? How do we keep up with the emerging technologies? I mean, there's IRE, there's TULSA, there's HIFU, there's cryo. You've kind of been on the head of technology for your entirety of your career, but maybe give us that perspective from your end.
[Dr. Jeff Cadeddu]
Well, I think that radical prostatectomy robotically or open hasn't gone away since the 1980s. I think the selection for patients is getting tighter and tighter so that we're not treating all Gleason 6 with radical prostatectomy anymore. As you know, my experience in kidney, I adopted ablation very early. I did not adopt ablation very early in prostate, but then maybe I missed the window there myself. But the point being is there's still a role for surgery and kidney cancer, right? We still do nephrectomies. There's still partial nephrectomies that are not amenable to ablation technologies in kidney.
I think it's kind of the same thing. We may see for sure, an appropriate well-defined role for focal therapy. We're going to see that ablative technologies will, again, focal or whole gland will certainly be for selected patients whether, there'll be elderly or not good surgical candidates. But I think we'll always see perhaps a diminishing role for surgery, but they'll always still be a role for radical prostatectomy, the high volume, high-risk patients, perhaps no different than it is in kidney ablation. The cryotherapy, radio-frequency SBRT, and it's still niche patients that are ideal for those treatments. And then everybody else has surgery.
So it may not be 100% of patients benefit from surgery, but we'll still have some degree of radical prostatectomy. Now, the next question then of course is can we get less and less invasive? I don't think that's the question as much as can we continue to improve outcomes? How do we continue to improve continence and potency so that the surgical expectations are no different than... The ideal thing was surgery shouldn't... For radical prostatectomy, it should be no different than appendectomy.
[Dr. Aditya Bagrodia]
Yeah, that'd be nice.
[Dr. Jeff Cadeddu]
Right. And if it is, if we can get it to be no different than appendectomy, then there's always going to be a role for surgery.
[Dr. Aditya Bagrodia]
Absolutely.
[Dr. Jeff Cadeddu]
So we just have to continue to improve rather than accept our outcomes. And we have. I mean, robotic surgery has revolutionized some of the outcomes and the playing field for surgery. We just need to continue to educate regarding that.
[Dr. Aditya Bagrodia]
Well, Jeff, I have always enjoyed learning from you. You've always been super thoughtful. And over the course of this hour, nothing different. A lot of good pearls for me to take home. Any thoughts for our listenership before we wrap it up?
[Dr. Jeff Cadeddu]
The most important thing in terms of a surgeon in the space of prostate cancer is to continue to stay up to date and educate yourself, whether it be adjuvant, genomic testing, whether it be the surgical outcomes, how to improve your surgical technique. Don't get in a rut and don't think the way you do it now is the way it's going to be done in five years. You've got to continue to evolve.
[Dr. Aditya Bagrodia]
That's perfect. Well, again, appreciate your time. Jeff Cadeddu, senior author of the AUA localized prostate cancer guidelines. All right, Jeff. That was perfect. Thank you so much.
[Dr. Jeff Cadeddu]
Thank you so much.
Podcast Contributors
Dr. Jeff Cadeddu
Dr. Jeffrey A. Cadeddu is a practicing Urologist in Dallas, Texas and is affiliated with multiple hospitals in the area, including Veterans Affairs North Texas Health Care System-Dallas and UT Southwestern Medical Center.
Dr. Aditya Bagrodia
Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.
Cite This Podcast
BackTable, LLC (Producer). (2021, September 22). Ep. 16 – Management of Localized Prostate Cancer [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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