Laurence Levine: Well, thank you very much, Alan. I really appreciate the opportunity to talk to you about this topic, which is certainly near and dear to my heart. I see an awful lot of patients with this over the last 30 something years. And surgery is one of the treatment options and in to my opinion it is the gold standard for stable disease. So let's review a few slides and then we can have some discussion.
Here are my disclosures. None of them really directly pertain to this discussion today. The indications for surgical reconstruction start with having stable disease. Now, that has not been clearly defined, but in general we say that one should wait to do surgery for about a year from the time of onset of symptoms, and yet some people may be ready earlier. We do want to make sure that their change in their deformity has stabilized. They have not really seen any significant change in the last four to six months before considering surgery.
We do recommend that if patients did have pain due to inflammation, that that pain be resolved, and of course, surgery would only be indicated if they had compromised or inability to engage in coital activity secondary to the deformity and/or due to inadequate rigidity. If patients have already tried conservative therapy, then surgery would be certainly an option. We have found from our experience that patients who have extensive plaque calcification typically end up needing surgery as non-surgical treatment doesn't tend to work. But anybody in the stable phase who has the desire for the most rapid and reliable result, surgery is the way to go.
Now, back in 1997, we published the very first surgical algorithm for treatment of men with Peyronie's disease, and this would be men who had rigidity, which was adequate for sexual activity with or without oral pharmacotherapy. So in those men, if the curvature was 60 degrees or less, and there was no hourglass or hinge effect, then a tunic plication procedure would be recommended.
On the other hand, if they had more severe deformity, greater than 60 degrees and/or a destabilizing hourglass or hinge, then incision or partial excision and grafting would be indicated. But the key, particularly for grafting, is to have excellent preoperative quality erections. We have found from multiple studies that we have published, that the best predictor of successful grafting in terms of post-op results is going to be their preoperative erectile state.
We then published another article in 2000 on men with inadequate rigidity where penile prosthesis would be recommended. We find that occasionally just placing the prosthesis alone will do a substantial amount of correction. I don't recommend the LGX type prosthesis as it does not typically have good rigidity for modeling, and therefore the CX 700 by Boston Scientific or the Titan by Coloplast would be the recommended inflatable device.
If we still have residual curvature, then modeling as recommended by Steve Wilson back in 1994 is used. And if there's still residual curvature or the patient insists on having a absolutely straight penis, then incision and grafting is typically indicated, particularly if the defect is greater than two centimeters. And in this case, I would be using TachoSil graft as it can be applied without having to be sutured in place and seems to be adequate in this circumstance.
Now the goals of treatment, if you compare them to XIAFLEX or collagenase, the only FDA approved non-surgical treatment right now for Peyronie's disease versus surgery, is that in surgery the goal is to provide a functionally straight penis, which would be 20 degrees or less, correct the indentation and/or hinge, preserve or improve rigidity. Basically, fix the problem.
On the other hand, with collagenase, you might not correct the curve entirely. You might reduce it, hopefully, and the literature would suggest that somewhere around 20 degrees of curvature correction can be expected that we see in most of the studies that have been published.
Can we avoid surgery? Yes, one can, particularly if they have mild-moderate disease and their responder to that therapy. But clearly both of these treatments may improve sexual function, reduce bother due to the deformity, can certainly improve self-esteem and self-image.
So as I like to say, patients need to know the truth about Peyronie's, and that surgery has at least a 90% likelihood of making the penis functionally straight, which we have defined back in a study we published in 2010 as being less than 20 degrees in any direction. That should not interfere with sexual function. XIAFLEX or collagenase has a 70 to 80% chance of reducing curvature by about 30%, but a very low likelihood of really correcting the curvature beyond 30 degrees, especially if you have moderate to severe curvature, which we would define as greater than 45 degrees.
And when properly selected, surgery, I find, has a low risk of complete erectile dysfunction. XIAFLEX, we should recognize, does not correct length loss, indentation, hinge, or erectile dysfunction.
So in this brief presentation, the conclusion would be to me that surgery remains the gold standard. Preop assessment is critical. We want to make sure they have stable deformity. We should measure stretch penile length before surgery and then postoperatively, because change in length can occur as a result of any treatment we do to Peyronie's. All men should undergo a penile duplex ultrasound to evaluate their deformity and their erectile status.
Informed consent and patient selection is key as it is in all medicine, of course, certainly in terms of proceeding to surgery. And I think overall plication is best when the curvature is less than 60 to 70 degrees and there's no hinge and the patient doesn't have any serious concerns about possibly some further length loss, which can happen more often with plication, grafting is certainly more risky than plication, particularly with respect to postoperative erection issues.
But the indications for grafting have been consistent now for over 25 years using that algorithm that I mentioned earlier. We need strong preoperative erectile function, a severe curve, and presence of hinge and length concerns would be indications to do grafting. And if the man does not have good erections with or without oral medication and has Peyronie's disease, then I think an inflatable prosthesis should be placed and then straightening maneuvers would follow to correct the residual curvature. And that would be again, in the man would refractory erectile dysfunction.
And so that's my quick review of the surgical approach.
Alan Wein: That was a remarkable amount of information in a short period of time. What are the risks of the surgery? I mean, what do you tell the patient beforehand the bad stuff that can happen?
Laurence Levine: Sure. Well, that's critical, of course, in something as first of all emotionally charged and devastating as any change that happens to the penis for a man. These patients come in, they're all worked up, needless to say. And we'll take them in order in terms of the simplest to the most complicated.
For the plication procedure and for the grafting procedure, I tell patients that there may be residual deformity, there could be recurrent deformity, which is probably, in my experience somewhere in the 2% range, where we might need to do something more after a surgical correction. So unlikely.
There could be some sensory changes, particularly if you have to mobilize the neurovascular bundle, which is almost always the case when you're doing grafting. But still with proper technique, the likelihood of having permanent, substantial loss of sensation is very low, in my experience.
There could be change in length. Again, men with Peyronie's, one of the most bothersome parts of Peyronie's is length loss and surgery could make for more length loss. So we talk about that as being a possibility. And that's one of the reasons why we recommend using plication for the less severe curve, because they're less likely to have length loss than if you're trying to correct a 90 degree curve with a plication.
We do strongly recommend post-operative rehabilitation using traction therapy, which we published on years ago, showing that this will reduce the likelihood of length loss with both plication and grafting.
Alan Wein: What kind of traction therapy do you use?
Laurence Levine: Well, there are several different devices out there. There's the RestoreX device, which is I think more convenient and easier to use. 30 minutes twice per day tends to be easier to apply. It's a little more expensive a tool. I tend to prefer what's called the PeniMaster Pro. It has to be worn for two to three hours or more per day, but is easier to wear. It can be worn to bed. And I think, just like braces on the teeth, they're not on there just a little bit of time. They're on 24/7 cranking away.
So a more prolonged, I think, traction has a greater likelihood of success, both post-operatively and even pre-operatively for correction of deformity. And then the final thing and most important thing that we address is ED. ED is going to be much greater risk in the man who needs grafting, which is why we insist that they have the best possible quality erections.
I always start when I'm seeing a patient, when I come in, do a duplex ultrasound. How does the erection we have just created in the office compare to the erection you have at home? And if they've got a strong erection and they say, "yeah, this is about the same as it is at home," or, "better at home," then I know that they would be a candidate for grafting.
And with that, and we, I think recently published on this as well, we found that men who have good preoperative erections have about a 4% chance of needing a prosthesis after surgery if they have good erections beforehand. But if they do not have strong erections but insist on going ahead with the grafting procedure, there's a 50% risk that they'll need to have a prosthesis later.
The other surgery would be the prosthesis, and we talk about the same things that we would use with any penile implant. Risk of infection, One to 3% is sort of the general number published in the literature. Mechanical failure of the device. Most companies now, I think, accept about a 20% 10-year mechanical failure rate, in which case the device can be replaced, or it can be left in place if a man doesn't care to have sexual activity anymore.
Incomplete correction of deformity is relatively rare once the prosthesis is placed, or recurrent deformity, again, highly unlikely when the device is placed properly and they do proper cycling after the procedure.
Alan Wein: If someone just has a graft procedure and then subsequently they develop ED, that's refractory to oral medications and even intracavernosal injection. Are the prosthesis more difficult to insert in someone that's had a graft or not?
Laurence Levine: Well, that's a great question because it comes up now and again. The answer is no. Usually if you've done a grafting procedure, it does not tend to obliterate the cavernosal space, and we can readily get our cylinders into that space, and we find that it's almost like putting in a prosthesis in a virgin case, because the patient has hopefully had their deformity corrected and now we're just putting the prosthesis in, either from a penis scrotal, which is my preferred approach, or from an infrapubic approach. Maybe a little modeling would be necessary, and we're off to the races. So it does not tend to be more difficult.
Alan Wein: So a graft alone or a graft with a prosthesis, how long until they resume sexual activity, assuming they did the modeling, etc.
Laurence Levine: Typically with the prosthesis, it'll be four to six weeks before we start cycling the device. If we're doing incision and grafting over the prosthesis, then it will be at least six weeks. Typically, what I do is, I leave the prosthesis partially inflated, maybe 50, 60% inflated, so they are in the erect kind of configuration for a couple of weeks during the early phases of healing. Then we deflate the device for a month, allow further healing to occur, and then we begin cycling at six weeks.
Without prosthesis, if they've had a grafting or a glycation procedure without implant, we start resuming sexual activity at six weeks. Typically, at two weeks we begin rehabilitation, which includes massage and stretch, and start using traction therapy at around one month after surgery, and they'll do that daily for three months, but can resume sexual activity at six weeks.
Alan Wein: If there's enough calcification on an ultrasound so that you can see it. Does that mean not to use collagenase?
Laurence Levine: No, not necessarily. We graded, established a grading calcification some years ago, grade one and two, which would be pretty much anything less than maybe a centimeter diameter calcification. One can use XIAFLEX. The more calcification, the more less likely you're going to get a good result. But people have shown that injecting around the calcification, you still can have some correction.
If it's so-called grade three calcification, one and a half centimeters in any dimension and maybe associated with severe indentation, then in my opinion, XIAFLEX is not indicated. We also looked at surgery after XIAFLEX, and we found that the majority of men who had failed... Who underwent surgery, who had also failed XIAFLEX, had already severe disease, meaning that their curvature was in excess of 60 degrees, they may have had grade three calcification, and/or had a severe hourglass causing a hinge.
Alan Wein: Great. Listen, that was terrific. Thank you so much for sharing all that information. Really appreciate it.
Laurence Levine: My pleasure. Of course.
Alan Wein: Thanks so much.
Laurence Levine: Great to be with you. Nice to see you.