DR. THOMPSON: So, question from the audience?

PARTICIPANT: Yes, I was going to ask, there doesn't seem to be anything like an objective response, then complete metastectomy (and this sort of goes along with the removing of the lymph nodes for bulky disease).

It seems now that we have technologies available to address sites of metastasis that were not accessible with standard surgical procedures, is there any plan for complete metastectomy plus or minus immune modulation, or immune modulation plus or minus complete metastectomy, in patients with a good performance status, for example?

DR. VOGELZANG: I'm one of those people who ardently supports metastectomy, although I think I dispute your claim that it is possible. In a large number of patients, there is mediastinal, subcarinal nodes. You can't get around bone mets. Maybe 15 percent of patients really with overt metastatic disease can be rendered free of disease. I bet you are not higher than that surgically.

Jim Kozlawski looked at this a while back in a nice review in Urological Clinics in North America. Across the board it was about 10 or 15 percent of patients could be rendered NED. So I don't think we are going to get there with surgery.

DR. BELLDEGRUN: All our patients are seen at the kidney cancer clinic, together with Dr. Figlan and myself, and as such, if they are being sent to nephrectomy, they are a candidate for surgery. So it's stress on us to deliver them back to the medical oncologist to give immunotherapy.

So whatever you can do, give me the darn surgery and resect safely, that's what you have to do. If you have 40 percent of your patients will not receive immunotherapy, whatever you will show will never be significant. So the idea here is to be as aggressive, but safe, so that the patient gets immunotherapy within months. So that's the answer.

And we felt ourselves how we gradually became more aggressive, because we followed and we learned whom to operate, and whom more importantly, not to operate on. And I think we have been quite aggressive. So resection metastases is something that you can do, and we will go after a lung or resect a pulmonary nodule if we do a thoracoabdominal incision if it is necessary.

DR. THOMPSON: Dr. Childs, can you quickly address that?

DR. CHILDS: So our protocols have been pretty much at the proof of concept level. So we have required that patients not be potentially resected into a CR, otherwise they would be ineligible. Although I think that minimal residual disease may actually be the ideal group of patients to be targeting with a non-myeloablative transplant.

There is clear evidence that tumor bulk translates into ultimately immunosuppressing patients through either secretion of factors that inhibit T cells, multiple other mechanism that have been described.

So ultimately in the future, taking patients that will certainly relapse, that have been resected to CR, and exploring allogeneic transplant seems reasonable. But at this stage that we are at now, we need to be able to evaluate them to be able to say that we have actually done something for them.

DR. THOMPSON: Thirty second response, please. The number one question or the number one trial that you would like to see occur in the next two to three years. Arie?

DR. BELLDEGRUN: Probably in comparison what is happening now is that the standard of care is the nephrectomy plus interferon, versus IL-2. So it's the combination of surgery plus interferon, versus surgery plus the IL-2.

DR. VOGELZANG: Either a combined anti-angiogenesis approach targeting multiple steps in the pathway, for example a CA9 and a VEGF inhibiting molecule. And moving VEGF or such things into head-to-head comparison with interferon or interleukin-2.

DR. BELLDEGRUN: You don't have even one CR to show us that one patient had a complete disappearance, and you are already moving to the next step.

DR. VOGELZANG: For the clear cells though, Arie, it goes right to the biology. It goes to right to the heart of --

DR. BELLDEGRUN: No CR's.

DR. THOMPSON: And the last word before we move to the next session.

DR. CHILDS: It's easy for me, because when you are a transplanter, and all you have is a hammer, everything looks like a nail. So hopefully, 3-5 years from now when we improve toxicity, we may think about doing a trial, randomizing patients for transplant versus IL-2.

DR. THOMPSON: Very exciting work. Thanks to all the panelists. I appreciate it.

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