 And with that, I would like to hand over to our next speaker, which is Axel Becks, who will talk to you on the topic of Sutter-Reductive Nefrectomy. Thank you, Victor, for the introduction. I also would like to thank the organisers who are inviting me to Dublin. As we are in Dublin, you may be all aware of this play, Waiting for Good Dough. And I think this question to the answer, are we any wiser now, where we are as elusive as waiting for this mystery guest? Sorry, forward is enough. As you know, there are ongoing phase three trials, and if we take these as the pinnacle of wisdom, then we could also close this session right now and go for an early lunch. The two trials ongoing, one is asking the role of nephrectomy, and the other one is looking at the timing of nephrectomy in a subgroup of patients that are, by diagnostic scores, ideal candidates for surgery. But the problem is, luckily, there's another definition of wisdom, and I can tie you a bit longer with that. So it's basically the knowledge of what is proper, reasonable, good sense of judgment. And because the question was not so much what is already known on this subject, but what is new in 2014, not much, actually. As I already said, those prospective randomized trials are ongoing, they're very difficult to perform. Tim Eisen already alluded to that. But there is emerging epidemiological and treatment shift data. We have larger real-world data sets, to which Danny Heng already alluded. And we're a larger body of retrospective studies. And from this, I allow the sort of wisdom ranking scale, which I would like to take you through. So I think wisdom number one is a stage shift. In 2004, 10 years ago, Flanagan, who was the PI of the SWOC trial that investigated site-reductive nephrectomy in the area of cytokine therapy, could safely say that about one-third of patients were primary metastatic at the time of diagnosis. Now, this has changed. There are data from Sweden, Germany, Netherlands, and you can see a gradual decline in the percentage. I discussed this yesterday with Griswold. I think we will have to see this in perspective. There is an increase in incidence. But the percentage of patients who present with primary metastatic disease at the time of diagnosis is declining. So actually, there may be some progress simply by detecting small arenal masses and the therapy we are doing. But this also poses questions for those trials which are ongoing. Then there's a treatment shift. Despite all the data we published, these are SEA data, so from large databases from the United States, and there is a sharp decline in the use of cytokine nephrectomy. And I added this red arrow, and it coincides with the introduction of target therapy. So I think that is what we are doing. This is us, we as therapists of renal cell carcinoma. And why is this? I think basically, because we already showed this, we've shown this curve here, that there is an improvement in survival of the target therapy. Most of these patients do have a decline of the primary tumor, something which has never been shown in the area of cytokine therapy. Maybe some individual cases with interleukin2 have been reported. But in most cases, you wouldn't see a decrease of the primary tumor. And so I think taken together, we see that there's longer survival, there's a decrease of the primary, but still we can't cure patients. So I think the field has already decided, for some of these patients, it's good to just continue to keep them on therapy, because we will not save their lives in the long run. Wisdom number three is, I think, retrospective is not prospective. Of course, I think we all know that, but I could fill this talk for the entire afternoon, showing one publication after the other on retrospective data on cytoreductive nephrectomy, some are better than others, like the one here of jewelry. They even looked at Kanovsky's score, and they could show a survival difference of almost 10 months between those who had operated or not operated if their Kanovsky was above 80 or 80. Likewise, you also have good retrospective data from the MD Anderson. They looked at patients with a primary tumor in situ, and in the lack of some of these prognostic scores, which are not the same as the Heng scores, but some of them are very similar. You could see that their median survival is 30.3 months. And that is quite interesting. So I think, why is this? The reason is simply, we are fishing in a pool of patients who have a favorable tumor biology with slow progression, no metastatic volume, no psychometoid features. I think a good performance are intermediate risk scores, and they are brought to nephrectomy, and then we retrospectively look at our databases and we come up with a patient population, B, who have unfavorable tumor biology, rapid disease progression, and probably they're never considered for cytroductive nephrectomy. So we really have to be careful and we interpret all the data as we have shown. Western number four, cytroductive, should be cytroductive. And with this, I don't mean you should take out as much as possible in very hopeless cases, but I think you should look at the patient, and we all know these candidates who have large primary tumors, maybe one or two lung nodules, and you don't need trials for that. That's already in the guidelines in very individual cases. If you're able to resect all metastatic sites, it can be potentially curative procedure. It may potentially program prolonged progression-free survival, and has the added benefit that it substantially delays the necessity for target therapy for these patients. But this also poses a problem because these patients, they may not be the majority, but these are actually the ones we have the questions about, and they will not be put into the randomized trials because of their appearance. Western number five is first do no harm. When I prepared this talk, I was thinking about showing a slide. I think we as surgeons know that the procedures of removing a primary metastatic tumor can be as divergent as anything else under the sun. You have large abdominal surgery, where patients are hospitalized for weeks, but you also have laparoscopic procedures where patients go home after two days and recover very quickly. But still, from large retrospective databases, we can see that the signal that the mortality rate is much higher in this group, which is almost one out of 10 for those who are above 80. And another thing we shouldn't forget is that what these patients need in the long run is medical therapy. And there are some retrospective datasets that looked at how many of these patients actually proceed to medical therapy. There were different reasons not to proceed, but in the sum, 15% of these patients couldn't go on, either because of rapid disease progression, following surgery, or even perioperative death. And this needs to be prevented. So wisdom number six, select wisely, another open door, I guess. But most of us wouldn't have problems with the extreme spectrum of the disease. On the one hand, you see this patient with a large primary tumor and low volume metastatic disease, where I think we all agree that cytoreductive nephrectomy is simply of benefit. And then on the other hand, you have these patients who are just looking at the volume of metastatic disease at other organs at many sites. The entire concept of cytoreduction is simply out of place. We've already addressed ICA performance status, and these data are already old. I like to show them therefore, because this is something we know since 20 years almost. From these interleukin-2 studies that patients who are in ECOG-2 or Kanovsky score below 80, 70, something, that these patients would not proceed to systemic therapy. But the problem is, it's a very crude measurement. And as you all know, you can be ECOG-1 and can still hover around this Kanovsky 80 somewhere below 80, because it's not just very much comparable. I think this is also where Benai is Kudye alluded to when he asked this question of making the ECOG score comparable to Kanovsky. And therefore, I think you should use validated scores. I'm going through this now a bit more quicker because we had already the excellent talk of Daniel Heng. We should realize that most patients who have primary metastatic disease already have this fact of time from diagnosis to treatment less than a year. So basically, the majority of those are probably intermediate risk and poor risk. And when we analyze these data, Daniel Heng has nicely shown that, but these are data from our own institute in a smaller group. We had this submitted to ASCO last year is that at the onset, so if you look at the group of patients who enter your hospital and whether you do an infractomy or not just when they present, the probability to survive two years and longer is 25.5% for intermediate risk patients, but only 2.9% for poor risk patients. What we also found is that the median overall survival time in this subgroup of patients with synchronous metastatic disease is six months shorter than reported in the IMDC database. So I think this is just a sort of summary of what we already heard and that you should make use of these prognostic scores to at least assess the survival these patients may have. And that brings me to my last point. I think significance and relevance are not the same, certainly not for patients. So an infractomy and life expectancy should be balanced. And again here, one of the best ways to figure this out is, and we had this already, is by prognostic scores and I completely believe in that, that if you have patients who have life expectancy of probably less than a year, maybe even two years, I don't know whether these are ideal candidates for surgery. So with this I would like to conclude. I think the other speakers already pointed this out, primary metastatic renal cell carcinoma or any metastatic renal cell carcinoma as a heterogeneous disease and therefore selection of therapy is key to success. I still believe even as a surgeon that systemic therapy is mainstay of therapy for the majority of patients and surgery is just an adjunct. That's what all these trials have shown. In the cytokine area, the median overall survival time that was added by surgery was three months in the SWAC trial and the combined analysis half a year. So that is not a long time, but it's a median time. So basically I think we should try to focus on these 25 to 30% of patients who are probably living longer than two years and this is where the research should focus on the next years. And poor prognosis patients are probably best treated primarily with targeted agents. I don't want to say here that you shouldn't do an effrectomy, but I would only select those patients who after some time like this conditional survival concept are still alive and are probably candidates for surgery. With this I would like to conclude and we can have a discussion later. Thank you very much.