 All right, so here's a 63-year-old white male who presents with abdominal pain, history of hypertension, and coronary artery disease, status post-bypass, sit back in 2001, four-vessel bypass, these are the medications, a tenolol beta blocker, lovastatin for cholesterol, isinopril for blood pressure, and an aspirin. CT chest and labs are within normal limits. Dr. Wood, just before we continue, I just, it may be confusing for some of the people that the biopsy showed on because I told them but the lesion was still treated. I know that we do it, some of you tend to do a biopsy separate from the time of ablation, others have a patient get biopsy prior to ablation. Whether or not the biopsy's being done for active surveillance or for diagnostic purposes prior to treatment can sometimes change how things occur. So had the biopsy been done prior to thermal ablation, thermal ablation may not have been completed. That's correct, and that's the challenge, and that's something else that we struggle with with patients here, particularly at MD Anderson, because patients usually come from far away. And so to tell them to come here, have a biopsy, wait three days to get a result, and then have a subsequent procedure. Obviously they want to economize their time and minimize the amount of hotel bills and so forth, and so to accommodate that many times we'll do the biopsy and then do the procedure, but in this case this patient probably could have gotten by without a procedure. All right, so good point, Brian. Bypass times four, CT chest negative, labs within normal limits. Here's the tumor. Here's another view. Dr. Karam, what do you think? Discuss all the options and recommend partial infractomy. How would you do it open? Robotic, what? This one I would do it robotic, just based on the location and the size of the tumor. It's small enough and peripheral enough and the kidney to do it. Would you biopsy, though? No. Okay, Dr. Matin, thoughts? No, I agree. I think it's robotic partial would be fine. Cameron, what do you think about ablating it? I think it's doable. It's on the larger size. I would probably put calipers on it and measure it carefully, but it's exophitic, which means that it doesn't involve the central portion of the kidney, so tumors that are more exophitic or grow out of the kidney are easier to treat. It's surrounded by intra-abdominal fat. There is nothing around it, so technically it's feasible. Does tumor size influence your choice of RFA versus cryo? Yes, it does. In fact, larger tumors are, there's a cutoff for the RFA. RFA is very effective up until 3.6, 3.7 centimeters. A good study showed that once you go one centimeter beyond 3.6 centimeter, then you have, by a factor of two, you reduce your effectiveness. All of a sudden, your effectiveness drops significantly, so people have tried cryoplation, and yes, you can create a very large ice ball, but it does require placing multiple cryoprobes and being very aggressive, and that also increases the risk of bleeding. The group at Mayo Clinic treats tumors that are as large as seven or eight centimeters. I think all of those patients really should go to surgery, but I guess if surgery is not an option. The largest we have treated probably about five or six centimeters. There are other adjuvant things we can do to enhance the ablation. We can actually get inside the kidney to run an angiography approach and block some of the blood supply to the tumor, and actually that creates a kind of blood deficient area, if you will, a hypovascular zone where the ablation is actually more effective. So yes, larger tumors can be treated if needed, but obviously if the patient is a surgical candidate, surgery would be a better option. So this patient underwent a right partial nephrectomy with intraoperative ultrasound. Final pathology reveals a right renal mass, renal cell carcinoma, nuclear grade two, four centimeters in diameter, confined to the kidney, margin of one millimeter. Dr. Delacroix, the margin of one millimeter, that sounds really close. Is that a problem? This is renal cancer, we're not breast cancer. One millimeter, yes it is close, but it really has no clinical implications. I treat this as a negative margin, nothing different. So the message is, I mean again, in trying to spare nephrons, any margin is a good margin as long as it's a negative margin. So this patient comes back for first year evaluation, chest X-ray CT abdomen are negative. The patient develops recurrent right flank pain, gross hematuria, and it's September of 2012, so two years after surgery. The meds haven't really changed, no interval change in past medical history. And here's the scan. So you can see here's the right renal remnant, and there's this rather large tumor hanging off the right renal remnant, extending to the body wall, and may or may not be involving the retroperitoneal musculature as well as the rib. Here's another view. Again, you can see lots of postoperative change, potential extension to the side wall here, but definitely a recurrent tumor present in the right kidney. And if you go back, it's kind of where the old tumor was, but perhaps maybe a new tumor, hard to say. What was his initial surgery? And the patient now had, I'm sorry? What was his initial surgery? What did y'all do? What did we do? It was an open partial? Yeah, okay. So the patient presents now with this, and then on CT scan, we see a nodule in the right lung as well as some nodules in the left lung. So patient had a localized tumor, four centimeters, resected as a sort of, what looks like an aggressive recurrence with pulmonary nodules. Dr. Karam, how would you approach this patient? So I assume this patient has a good performance status, and except for the growth cemetery? Correct. I would offer the patient surgery. Number one, he has the bulk of the disease or the cancer is in the kidney and the abdomen area, so I would resect all of that aggressively. The bulk of the disease is there, so that's where we should go. And the other thing is the patient's symptomatic, the patient has bleeding in the urine and surgery will take care of that as well. And then give the patient a break and then refer him to our colleagues with medical oncology to offer him therapy. Any role for biopsy here? Biopsy of the primary tumor or biopsy of one of the lung nodules? No, I think it would be safe to presume it's the same type of tumor, and even if it's not, the patient's still symptomatic and good performance status and has a problem in that kidney that needs to go away. So I would not biopsy the patient. All right, you refer the patient to Dr. Taneer prior to surgery. Dr. Taneer, how would you counsel this patient? I agree with Dr. Karam. I would go with surgery upfront. For the reasons Dr. Karam mentioned, the bulk of the disease is in the kidney or the remnant of the right kidney. The patient is symptomatic, is bleeding. I would do surgery first. Michael, any difference from that? Would you recommend surgery? I would recommend surgery. And I guess we're kind of alluding to the fact that there's not a lot of data for cytoreductum nefrectomy. In our current era, there were two trials that had virtually identical inclusion criteria in the so-called cytokine era that showed a benefit in terms of overall survival for cytoreductum nefrectomy. We're presuming that there's that benefit now, although there will be several trials. Carmina included that may answer that question. And then in addition, as far as our new targeted therapies go, most of the patients in those studies, so 80, 90%, had had cytoreductum nefrectomy or nefrectomy one way or another. So we're presuming there's a benefit. I think for the people in the audience, we've all of a sudden introduced this new word, cytoreductive. We should just clarify. Everything you've seen up to this point has been renal masses without disease that has spread somewhere else. Cytoreductive nefrectomy is when you have a very good idea and you can see disease that's spread elsewhere, should we be treating the primary tumor? And that's what we're discussing here. Thank you. Let them know. So the patient undergoes cytoreductive nefrectomy. It's clear cell histology, T3A. Patient returns in follow-up six weeks later, has same pulmonary nodules that have slightly increased in size. Michael, what are you gonna counsel this patient? What are you gonna recommend? So I was trying to remember the patient's comorbidities and things like that, but I think depending on the patient's comorbidities. Hypertension and coronary artery disease status supposed to bypass. Yeah, so we're always thinking whether high-dose interleukin-2 is an option, probably based on the patient's history, I would be concerned that that patient could tolerate the different fluid shifts associated with that. If the patient were motivated, we could pursue further workup, including cardiac echoes and pulmonary function tests and things. Again, we're assuming we've removed the bulk of the patient's disease in the kidney and there are only some several small bilateral pulmonary nodules. I think most likely, though, the case is gonna be either number two or number four, thinking about our VEGF receptor TKIs, Sunitinib or Pazopinib, or certainly clinical trial. This is probably a good or intermediate-risk patient, and that would be level one evidence or standard of care. Did you do the nephrectomy through the previous flank incision or did you go through abdominal incision? Abdominal incision. And was it involving the liver, no? No. Dr. Tiniar, what are your thoughts? I agree with Michael. The patient is not accounted for high-dose R2 because of coronary artery disease and bypass. He's at risk of having cardiac arrhythmias and potentially fatal complication from that. So the options would be target therapy. I prefer participation in the clinical trial. It depends on the patient where the patient lives and if the patient's gonna be followed at MD Anderson or followed up locally. I think it's always more convenient for a patient to take an oral agent. So while B. vicissimab plus interferon is an option based on level one evidence similar to synitinib and pazopinib, I think you're given the patient two parenteral agents, one IV vicissimab and the other one is interferon injections. So the inconvenience, the cost of that would make me, if the patient is not interested in clinical trial or cannot come here, then I think synitinib or pazopinib would be the two options. Which of the two? I think data, they're comparable in efficacy. I think one would look at the patient's liver function test, history of any liver disease, where the risk of pazopinib having liver toxicity will be higher than that will be sway me towards giving them synitinib. And then if again, the patient wants to follow up locally, I think it's always important for the patient and for our professional relationship with our colleagues who refer patients here is to discuss the patient with the local oncologist. If the local oncologist is comfortable using synitinib then I think synitinib would be fine. If they prefer to use pazopinib then I think pazopinib is fine. So are the two equivalent, essentially? I think in terms of efficacy, there is a trial that was presented last year in Europe. The compares trial looking at both agents in a phase three trial that included 1100 patients. The efficacy was comparable. So that trial was designed with a primary endpoint non-inferiority based on progression-free survival, which means the time from initiation of therapy until there is disease progression or death, the two arms, the two drugs produced basically similar or comparable results. In terms of toxicity, I think each drug has its own adverse events. Synitinib, for those patients of you who have taken it, is associated with more fatigue than pazopinib overall. Pazopinib, as I said, is associated with more liver toxicity. I think they both produce about the same in Daria, although synitinib causes more hand-foot skin reaction, which is the blisters, calluses on the hands and feet. But I think synitinib has been on the market longer, so it was approved in January 2006. Seven-plus years, I think there are patients who are survivors past five years on synitinib. I think the follow-up with pazopinib is shorter, so I think that should also be taken into account. So it remains to be seen whether five years from now the two drugs produced the same fraction of patients who are alive past five years. But for all practice purposes, I think they're comparable in their efficacy. Okay.