Jenny Donovan: This is a question about quality of life in the surveillance group. Those that did not progress benefited greatly by avoiding radical treatment, but many of those who progressed experienced a longer time on androgen deprivation than the surgery and radiation group. How did their quality of life differ compared to the radically treated patients?

It's a very interesting, important question. The analysis in the paper shows that the patients who stayed on active monitoring avoided the impacts of radical treatments, the sorts of impacts that we showed earlier. We did actually look at some aspects of overall and cancer-specific quality of life.

That did not show a difference in the active monitoring group. There was no difference between the active monitoring group and the other groups in terms of those sorts of cancer-related, quality of life issues that you might expect from androgen deprivation.

But it is an important issue and we do want to look at that more closely. We're now setting up an analysis to look at the quality of life experience of the men who went on to have progression and additional treatment, because there aren't really very good data about men going on to ADT early on.

Nathan Roundy: In the support groups, we have a lot of men who really complain about their side effects from ADT.

Matthew Cooperberg: Yeah. This again, I would say, is something that can be managed. Well, not entirely. Some of the side effects of ADT are somewhat unavoidable. Many of them can be managed or at least ameliorated. I would also make the point, there was a question about diet. Diet and exercise are both essential for optimal management of prostate cancer in general.

I would say, for men going on hormonal therapy on ADT, there are a few questions less controversial in all of prostate cancer than the benefits of an aggressive exercise regimen for men on ADT, to help ameliorate both the physical and the mental side effects of treatment.

Jenny Donovan: Both of those things also enable men to take more control of what's happening to them. A lot of our men that we interviewed talked about wanting to change their diets and do exercise and things to keep themselves very healthy in a general sense, as well as for their prostate cancer.

Matthew Cooperberg: To this question about why we don't use diet to manage the cancer, that's an active research question going on at UCSF and elsewhere. Does an aggressive diet actually change the biology of the cancer? The answer is it might.

It's hard to show a clinical benefit because as you can see here, 15 years into ProtecT, we still only have a handful of long-term events. It takes a very, very long time to get clinical answers here, but we are seeing impacts on the cancer biology.

Freddie Hamdy: Matt, if I can make a comment about ADT?

Matthew Cooperberg: Please, please, please.

Freddie Hamdy: I'm personally trying to grapple with an interesting question, and that's the timing when ADT is given to patients. There's a very wide variation amongst physicians globally, and my personal feeling is that ADT is not infrequently given too soon, and of course, without knowing when the benefit is going to be.

Of course, ADT does have side effects that we all know about. As Jenny was mentioning a minute ago, it is not a nice treatment to take. There needs to be some order put into the timing of when ADT should be optimally started.

Matthew Cooperberg: That's an outstanding point. I think the trend over time has been that we've been starting it later. I think there's been less knee-jerk early start of ADT. However, this is an area where PSMA PET is changing things because we're finding metastatic disease much sooner than we would have. This distinction between M0 so-called and M1 has always been a little bit arbitrary, and we are affecting what's called a stage migration.

Meaning we're transferring men from the M0 category to the M1 category just because we have a new tool that lets us look harder. Those men who are found to have early metastatic disease are getting not only ADT now, but intensified therapy with things like abiraterone, first-generation AR antagonists, and chemo; it's a whole different conversation. But men who do not have PET findings, especially with a slowly rising PSA after surgery and radiation, typically do not need early ADT.

If they do go on ADT, it can very often be intermittent, meaning you treat for a period of time, come off it, take a break, and then go back on it for a time. Wonderful. Why don't we have each of the advocates whose question these are, go ahead and read them? I think it's good to preface them this way.

Bruce Zweig: You did have some people assigned to active monitoring who normally wouldn't be. They have higher Gleason scores, but they were randomized to it.

Do you think that might've skewed the results in any way from what happened in the normal population?

Freddie Hamdy: Thanks, Bruce, for that question. The number of men who had Gleason 4 and 5 in ProtecT was very, very small, it was about 2.5%. We don't think that excluding them or including them would have made a massive or significant difference that would change the findings that we've had. The bottom line is that ProtecT cannot really make any conclusions about high Gleason, except that we continue to believe that high-grade disease, Gleason 4 and 5, is not good disease.

It doesn't necessarily grow very fast. But the world of literature and experience suggests that these high-grade cancers need to be treated sooner rather than later, and sometimes with multimodality approaches to it. I think we just need to clarify that ProtecT is not about high-grade disease. It's about low and intermediate-risk disease. Matt, do you want to add anything to that?

Matthew Cooperberg: Oh, no, no, I agree completely. I think, again, like we've talked about, there are some patients who had high-grade disease on final prostatectomy who had been under-sampled.

In a way, it's remarkable that the difference between the metastases curves is so small, even knowing that many of these men were under-sampled. It just stresses the point that if you've got low-risk disease by a contemporary diagnosis, surveillance is the way to go.

Freddie Hamdy: But you mentioned PSMA PET, and I think we routinely in our clinic, we do use PSMA PET in patients with high-grade disease, whether they seem to have localized disease or not. It is very helpful in staging, continuing the staging. Yeah.

Stan Rosenfeld: Dr. Donovan, did the questionnaire ask men if they were using aids for their erectile dysfunction: vacuum pumps, injection therapy, et cetera? Because to me that would make a major difference.

Jenny Donovan: Yes, thanks for that question, Stan. It was something we thought about, but we didn't have the resources to collect the data specifically about the use of the different devices and aids and so on, but all men followed standard practice at the time.

Actually, all the men involved in ProtecT saw a nurse at least every year, and they were able to discuss with a nurse and a urologist, if they wanted to, whether to have any of these devices and things. What we heard in the interviews was that some men use them, some men didn't.

Some found them useful, some didn't. These data are effectively showing you, on average, across the groups, the effects of these treatments with and without the aids that they could use. We don't have the detailed data, but we have these average effects.

Stan Rosenfeld: As you're saying, it's all averaged out. Maybe a future study can differentiate and differentiate between which aids gave which satisfaction, because I think that's really important that men know that.

Jenny Donovan: Yes. It needs to be a specific study to look at that issue.

Stan Rosenfeld: Yeah.

Jenny Donovan: Of course, each man's situation is different, and would need consideration with your clinician, closely monitoring.

Stan Rosenfeld: I just want to say for everybody listening, that I chose my treatment back in 1998, based on my research, on showing that I could get good erections with injection therapy. I, therefore, chose not to have my nerves spared, which was a risky choice to have.

But I chose not to, because I knew that I could get erections anyway. I think that kind of information prompts patients to use their best judgment, their personal preferences, along with their spouse or partner. It's important information for men to have.

Jenny Donovan: Yeah, absolutely. It is very much an individual choice.

Matthew Cooperberg: I would say, I would just emphasize what we said before too, that side effects can be managed. Resilience is a bit of a double-edged sword after treatment. I think we see many men years out from treatment, who have been using two or three pads a day, every day since surgery, and have decided, "Well, this is what life is like."

They say they're fine with it and they shrug about it. I say, "My colleagues could probably do something for you." They say, "No, I'm fine." But when pressed, the reality is that the interventions that we have are often pretty straightforward. Things like sling procedures for minor incontinence, even an artificial sphincter, which is more of a procedure, but is an outpatient,

Or one night at most in the hospital procedure, and can be highly, highly successful in improving quality of life, should be considerations. These should at least be conversations. The same is true for management of sexual dysfunction or bowel dysfunction after radiation.

Freddie Hamdy: I just want to comment here, Matt, that we have here, just on this table talking, we have wonderful examples of survivorship. Survivorship is a science, which I think is under-researched. Everybody thinks of the immediate, what's happening immediately when you're diagnosed with cancer.

But in the case of prostate cancer in particular, people live such a long time with or without treatment that surviving this cancer and what happens over a long period, 15, 20, 25 years, is such an under-researched part that I would like to see a lot more work done in that area.

Matthew Cooperberg: Absolutely, absolutely.

Stan Rosenfeld: It's pretty clear to me, looking at the study, just looking at an active surveillance, that just age alone is contributing to many of the side effects.

I'm just wondering if you've come to the same conclusion, or do you think we need another study that compares patients with prostate cancer with the population at large?

Jenny Donovan: Yeah. Again, it's an interesting question. The analysis that I've shown shows you can compare the different treatments with each other. Because it's a randomized study, there's the same number of different men of different ages in each of the groups. But we did look specifically at this in the six-year data, as we did investigate the impact of age there.

Interestingly, we found that actually, of the main data items that I mentioned earlier, only pad use for urinary leakage was affected by age. Older men tended to use more pads for leakage than younger men, but the erection problems were similar for older and younger men. The bowel issues were similar for older and younger men.

It's not quite as simple a relationship as one might think, but obviously, some aspects of the urinary and sexual and bowel system do deteriorate over time with increasing age. But in terms of the effect, the interaction with treatment, we did actually look at that at six years and only saw that the difference was really for pad use.

Matthew Cooperberg: I might field one of the attendee questions here too, since it's relevant, which is about prostatitis and enlarged prostate. Is that an indication to choose surgery over radiation after years on active surveillance? It certainly is the case that many men with prostate cancer also have BPH, and can have some pretty terrible, obstructive symptoms, having nothing to do with the cancer.

But just because they have benign growth of the prostate, which is even more common than prostate cancer as men get older. It is the case that when we do a prostatectomy for men who have a higher risk prostate cancer as well as BPH, we actually can often yield better urinary function at the end of the day, than the man had going into surgery, because we're killing two birds with one stone, as it were.

The radiation results, I would say, are a little bit more mixed in that situation, but this is still not an indication to do a radical prostatectomy for somebody that otherwise has low-risk disease, except in very, very uncommon situations. I would say for the most part, men in that situation are better off just having a BPH procedure like a TURP or a HoLEP, or something like that.
We continue to follow the cancer, because the overall risks and the risks of sexual side effects, in particular, are much, much lower.

Freddie Hamdy: But also, Matt, just on that, what we observed, at least anecdotally, is when they are on androgen deprivation therapy for three or six months, that improves their outflow obstruction symptoms.

Matthew Cooperberg: Yeah. Yeah, for sure.

Freddie Hamdy: Then they get the radiation, and as you say, the results are mixed at the end.
I agree with you, it's not an absolute indication for doing the radical prostatectomy if you have BPH.

Bruce Zweig: I was wondering about your results for patients 65 and over, as there seems to be a tendency to favor radiation for them. I'm just wondering, and that was with prostate cancer source mortality as your measure.

But if you look at overall survival, did you look at that at all for the 65 and older? I know it wasn't in your pre-specified analysis, but if you look at overall survival, does that change things?

Freddie Hamdy: No. Let me tell you, with this, this is a very interesting finding. First of all, is to caution about interpretation again, because this is a subgroup analysis, and the numbers are very small, as Matt alluded to in the 10-year paper, when the editorial suggested that the very, very small numbers indicated that one treatment was better than the other, I think the numbers are very small.

The second thing is that most other studies suggest that beyond the age of 65, that doesn't seem to be a significant benefit in treating patients radically. We've shown something different, perhaps for the first time, which is actually very useful. Because being older than 65 should not stop or prevent patients from receiving treatment, which could make a difference to the cancer outcome at the end.

I think we need more data to be able to analyze that particular issue more carefully. It actually doesn't surprise me, because if you look at epidemiological data of patients who present with prostate cancer without screening or who die of prostate cancer, that tends to increase with age, not decrease. As the life expectancy now is increasing everywhere in the Western world, we are going to see more older patients get the disease and benefiting from radical treatment.

It's a balance, but it's an indication that we should be more attentive to patients who are older with prostate cancer, but it opens a whole can of worms there. I don't know, Matt, what do you think?

Matthew Cooperberg: I agree completely. I think when we've talked about prostate cancer diagnosed in older men, there's a lot of question about what the screening history has been as well. Why are we finding prostate cancer at 73 instead of at 60? I think it depends what has happened in the intervening years. Men who have had a PSA every few years, and it's always been stable, and then it goes up, and we find prostate cancer in the men's 70s.

It's very different from a man who gets a first PSA in his 70s and is found to have a pretty bad cancer that has been missed. I would really stress the point that this is increasingly clear that the best way to screen for prostate cancer, is to check a baseline PSA relatively early in life. For the large majority of the population, literally about 75% of men who get a baseline PSA at 45 or 50, they're pretty much done, or at least done for the next 20 years.

We've got quite good evidence on this now, to avoid delayed diagnosis of high-grade cancers, which I think was even more common in the era of ProtecT accrual. But it's still an issue today, because PSA testing is still done mostly on men in their 60s and 70s, which is not optimal.

Leszek Izdebski: Your paper mentioned that Gleason grade group was used to pre-specify some of the groups. Obviously, biopsy is still imperfect, but during that period of time, when it was not driven by MRI or ultrasound, in many cases, was even less perfect.
There is a big question, obviously, how potentially this misassignment, so to speak, of the subgroups could impact the results of the study.

Freddie Hamdy: Yeah. No, it's a great question. Thank you. I think the question really illustrates the fact that the study has taken that long to complete and to finish, and to yield results, and then the world moves on at the same time. The answer to your initial question is, have we considered pre-specified by baseline? The answer is yes. We've only considered the baseline biopsies to subdivide the pre-specified group.

Not by pathological staging or grading after radical prostatectomy, because we only had that data for the man who received surgery, so we couldn't do it. Having said that, we know that because it was a randomized design, that the upgrading and the upstaging that we found in men who received surgery would be reproduced in the other two arms. For example, we had upstaging following radical prostatectomy of about 29% of patients.

So, just under a third. We expect that, therefore, in the radiotherapy arm and in the active surveillance arm, that monitoring arm, we also had roughly the same number of men who would've been upstaged. Was it adjusted? No, it was not adjusted. Is the new diagnostic pathway using PSA followed by a multiparametric MRI? At least in Europe. I think it's catching up in the US, Matt can update us on how far this has gone.

But using the multiparametric pre-biopsy imaging and then using targeted imaging, either using cognitive or fusion biopsy techniques, I think that will have allowed us to make less misassignments of the grade group. There's no question about it. What would it ever look like? I don't know, but I think we have demonstrated clearly that the risk stratification of patients who were enrolled and recruited to ProtecT, was not very good.

It is likely that if we use now the current diagnostic pathway, that the assignment will have been different.

Leszek Izdebski: Obviously, the surgical techniques have improved, and have been improving consistently, and radiation therapy has been improving.

Especially on the side effects, I'm wondering, has there been any way of looking at the data to compare the results of surgical intervention done 10 years ago versus five years ago, and similarly for radiation therapy?

Jenny Donovan: Yes. Again, a very interesting question. We aren't able to do that within our study, but what you can do is compare our study results with some cohort studies that have been set up more recently. After the ProtecT data were published in 2016, a couple of big cohorts in the US were published that looked at patient-reported outcomes using the same measures that we did and with essentially the updated treatments.

Radiotherapy with the IMRT, brachytherapy, robot-assisted prostatectomy, and active surveillance. What's interesting, when you look at those cohorts, is they weren't randomized, so they have biases. We know that older, sicker men tend to be offered radiotherapy and younger ones, surgery. They tried to account for those things, but may not have done so perfectly. But when you look at the data on the side effects, the patterns of the side effects are remarkably similar to our findings.

There's also been a trial comparing robot-assisted prostatectomy with open, and that showed very similar functional outcomes. In terms of the side effects, the new treatments have not really changed things in terms of the functional side effects. I think most people think that the modern radiotherapy might have lesser effects, but they're actually very similar, when you look at the data for our study. Our study, we had hormone therapy, ADT, with the radiotherapy.

If you don't have the hormone therapy with the radiotherapy, then obviously you don't have the effects of the hormones. But actually, yeah, the side effects are not that different.

Matthew Cooperberg: Let me just get to one of the other questions in the Q&A, just to emphasize that point. Just to confirm, all the patients that got radiation in ProtecT did get a short course of ADT?

Freddie Hamdy: Yes.

Leszek Izdebski: The follow-up question on the radiation therapy, the lack of difference, do you think it's mainly because the doses were lower for the ProtecT study than current typical radiation is?

Or do you think it's just in general radiation therapy side effects seem to be always very similar?

Freddie Hamdy: They had 74Gy, so they were not low radiation. I know people have gone to over 80. What the radiation oncologists mostly focused on is reducing toxicity, because even very recently there's been a suggestion that if you give even less doses, you get similar outcomes. I think we are not looking at cancer outcomes, we're looking more at reducing toxicity for patients.

For surgery, the common denominator is the individual skill of the surgeon, and it is the surgeon that makes the difference rather than the technique. We see bad outcomes from bad open surgeons. We see bad outcomes from surgeons who use the robot. I think it's misleading to think that just because you're going to have a robot-assisted prostatectomy, you're automatically going to have a better outcome.

The robot does not make a bad surgeon a good surgeon. I think that's really important, and there have been wonderful outcomes from open surgery as well. Matt, I don't know if you want to comment?

Matthew Cooperberg: The robot does not even make a bad surgeon an average or acceptable surgeon. That, we've seen over and over again, and I could not agree with that point more. The robot does decrease blood loss, it does decrease pain slightly. It decreases hospitalization slightly. But if you're a surgeon who's done 1,000 open prostatectomies, do open number 1,002. You'd rather not be robot number six for that surgeon.

I really would stress the point that I made earlier, which is if you're seeking treatment, push your team on their own outcomes. If they don't know their own outcomes, you should be going somewhere else. The practices, which are really specialized in prostate cancer, we all track these quality of life outcomes very specifically within our own practices, and that's essential.

With that, I realize we're at the hour. If everyone has a few minutes, we can go through some of the questions from the field. Maybe to pick a few out of the Q&A first here. First of all, there is a comment that this is wonderful work, and how did you get it funded? There are amazing things that happen out of the UK that don't seem to be possible in the US.

Freddie Hamdy: It's a long story, it's an adventure. Jenny and I, and David Neil, together, we started to pull together the idea of ProtecT and to get it funded as early as 1994. To cut a long story short, it took us five years to get it funded, but only as a pilot. Because, as you said earlier, Matt, nobody could believe that we would be able to detect men with prostate cancer and randomize them to a non-intervention arm in active monitoring.

Nobody believed that we could achieve that. We were given funding, modest funding, to do a pilot study, a feasibility study, and it took us two years instead of one year. It was largely through the qualitative work about recruitment and the patient perception and the recruiter perception that Jenny was leading, that we were able to succeed in getting the rates of 70% randomization by the end of the pilot.

When we did that and achieved that, then the door was open for us to get formal funding, and the funding ended up coming from the UK government. The NIHR, which is the equivalent of NIH in the US, did not exist at the time. It was the Health Technology Assessment Program, and we were given then the funding competitively from that organization and the UK government.
Yes, it was a long adventure. Then we needed extensions about four or five times, and eventually, we got there. NIHR flags it as the most expensive study that was ever funded.

Jenny Donovan: The breakthrough happened when we audio-recorded what the urologists were saying to the patients about the trial and the diagnosis, and the treatments and so on, and what the patients said in response to that. Then I interviewed patients afterwards and it was listening to all that material that we discovered how best to present the study.

Then we trained the urologists and the nurses because we discovered when we first listened to it, that the urologists described surgery with great enthusiasm at great length. They described radiotherapy with some enthusiasm, but not for very long. Then they basically just said, "Oh, and there's this other treatment that isn't really a treatment at all for older men."

We had to then discuss what active monitoring was. We had to create it. Then once we worked out that, then the issue was describing the three treatments with equivalence, which was what was the truth. Then we listened to what the men said about that, and then they came along and agreed to be randomized.

Freddie Hamdy: Yeah, it was reaching equipoise. It was getting the nurses to randomize, having doctors, and keeping on training the recruiters, so that they have reached that level of equipoise. These were the main things. Sorry, you had a question, Matt?

Matthew Cooperberg: Will they fund a 20-year follow-up?

Jenny Donovan: We hope so.

Freddie Hamdy: At the moment, no, but yes, we've been invited to apply for a follow-up.

Matthew Cooperberg: There are a couple of questions here just on definitions, just for clarity. Localized prostate cancer, first of all, is prostate cancer that, as far as we can tell, is still in the prostate. For men who are diagnosed with low-risk or the lower end of intermediate-risk disease, the risk of metastasis is extremely small. We usually don't look for men who have high-risk disease or have the higher end, intermediate-risk disease.

There is that chance. Historically, we would have looked with a bone scan to look at the bones and a CT or MRI to look for lymph nodes. These days, in more and more clinical settings, PSMA PET is the way to look for distant disease. Cancer that has spread beyond the prostate is considered non-localized. In between, there's cancers that get outside of the capsule of the prostate but have not spread to other parts of the body.

We might call those locally advanced or sometimes regional, but they're still potentially curable with surgery and/or radiation therapy. But those are well out of the low-to-intermediate risk territory that we're talking about with ProtecT. Just to emphasize the point too, there's a couple of questions about what active surveillance means, and I would say this has evolved quite a bit.

Again, when ProtecT launched, surveillance was pretty uncommon, outside of only a handful of academic settings. UCSF has been doing this since the mid-'90s. Johns Hopkins, Toronto, there were a few centers that have been doing this for a long time, but it was very much an academic curiosity back when ProtecT was being planned. For a long time, we had a standard protocol at universities like UCSF where everybody got a biopsy every year or every two years.

These days, there's a lot of interest in trying to deintensify surveillance for men who have really low-risk disease. I can speak to the protocol at UCSF, which is when we diagnose a patient with low-risk disease or they come in from the outside, we will do confirmatory testing. We'll get an MR if they've not had one, we'll typically do a repeat biopsy within a year to make sure we have not under-sampled the cancer.

If we confirm low-risk disease at that point, the goal is to do as few biopsies as possible. If the PSA is stable, we will follow with imaging. If PSA plus imaging looks good, we really try not to do another biopsy for 4, 6, 8 years, in some cases. There's a lot of research ongoing in terms of using novel tests like genomic tests and biomarkers to do even better, and figuring out who really doesn't even need all these biopsies.

On the other hand, for the relatively small proportion of men in whom a cancer is growing relatively aggressively, we want to find those early and be able to intervene while the cancer is still curable. But it does look a little bit different from place to place, center to center, and I think it's increasingly tailored from patient to patient.

Freddie Hamdy: Yeah, so if I could just add to that. The other thing we would add is risk evaluation, particularly if there's a family history, we do more due diligence with the patient. If they have a significant family history, we get them in for genetic counseling to see if they need to be tested for some of the mutations, which are BRCA1 and BRCA2. Because there is evidence that these men are more likely to develop aggressive disease in the long term.

I would add to that, we would do practically the same thing. We do an evaluation, and then we would repeat the imaging at one year. Repeating the biopsy will depend on changes in the imaging. We do not use the biomarkers that you mentioned. I think they still need more validation, more evaluation, and they're not reimbursed anyway. The philosophy of active surveillance, which we've called active monitoring, but after quite a length of time, we changed the terminology.

Again, that's credit to Jenny's work in recording the things. Watchful waiting is something that has a different definition now. We have had patients saying, "I don't want this watchful waiting business, because it means you watch while I die." That's really helped us to change the terminology from conservative management, I think, to active monitoring. Patients need to know, which is true, that they are being actively followed up.

The purpose is not to delay or not treat the patient, or be defeatist about the disease or dismissing the disease. The purpose is to keep every patient in a window of curability, if they need to be treated and cured. It's a fine balance between protecting their quality of life from the side effects of the treatment, to not missing that window of curability where they would not suffer the consequences like metastasis in the long term.

That's a fine balance, which is challenging at the best of times. Jenny, do you want to say anything else about that?

Jenny Donovan: No, I think you've captured it perfectly.

Matthew Cooperberg: I would really emphasize this point about how wide the window of opportunity is for cure. Again, we see these delayed treatments in surveillance, and that is absolutely fine. I, and many, would rather have, I'd rather have my prostate treated at age 69 than 59. I'd rather have it treated in 2032 than 2022. Treatments continue to improve. There's a lot to be said, even for men on surveillance for a year or less.

That time to come to terms with the diagnosis, to feel that he's not being rushed into treatment. There are great studies in this. Satisfaction is better, treatment regret is less with even a relatively short interval of surveillance. I might make one comment on watchful waiting since you mentioned that. I heard a great talk from Caroline Moore, one of your colleagues in the UK last year, who talked about when did we graduate men from surveillance to watchful waiting?

When do we actually say, "Listen, this is not going to be an issue"? You get to 80 years old with six years of surveillance under your belt. Do we really need to keep doing MRs and biopsies and all this? It's something that we don't actually talk about that much in the US, but getting to that point where we can say you're good is something that I think we're trying to figure out based on age, life expectancy, and everything else.

I cannot tell you how much I appreciate the time that Professor Hamdy, Professor Donovan, and our advocates have put into both planning this event and your time over the last hour and a quarter here. I think this has been wonderful. I am very happy to see how many have joined, how many attendees we've had. If this proves a successful format, we are hoping to do this every quarter, maybe every couple of months.

As research studies come out, we will have other authors from other studies come on with other commentators and patients, and continue these types of conversations. Thank you, everyone who has joined us. Thank you very much once again for all of our panelists.

Freddie Hamdy: Thank you very much.

Leszek Izdebski: Thank you very much.

Nathan Roundy: Thank you.

Stan Rosenfeld: Thank you.

Freddie Hamdy: Thank you.

Bruce Zweig: Thank you, Doctors.

Freddie Hamdy: Bye.