 Good morning. It's a great pleasure to be back and thank you for inviting me and allowing me to sample the latest Chicago hotels as we do this So I'm going to speak in a very practical way about where I think we are with active surveillance today And I want to start out by just being sure we're all on the same page with the definition of a small renal mass Which is an entity it's the clinical entity that leads to a diagnosis of kidney cancer in more than half of our Cases now and these are asymptomatic and I would say less than four centimeters That are incidentally detected on imaging and they look like renal cell carcinoma. But importantly, they're not always renal cell carcinoma and we've known for a long time that these can grow very slowly We know the three centimeter rule in the VHL population that Marston line a hand and company have Supported with evidence that never seen a metastatic event in a growing VHL renal cell carcinoma, which are clear cell as you know Under three centimeters. We've known that there's been an autopsy prevalence of this entity which indicates slow growth and we grew up as Students learning about Bell's adenoma, which were small RCC's found incidentally and were categorized as different than renal cell carcinoma and lastly the Bosniak observations, so There are a number of autopsy reports anything that we find incidentally at autopsy Indicates that there is a an indolent nature to it. We know that full well from prostate cancer Bell's adenoma has only Relatively recently dropped out, but it was an autopsy observation as well that there were rarely metastatic events and then most recently Morton Bosniak at NYU looking in the x-ray bags of Patients undergoing kidney surgery would find old films that Showed that there was a mass in the kidney and of course in those days They weren't always as Quality as that we have now, but we learned that these tumors can be on occasion present for a long time So that led us in Canada and others have done somewhat similar work looking at Active surveillance in that means actively watching the tumor and treating it only if it progressed in a cohort of patients across the country and we published that and Like others we showed there was a relatively slow growth rate So that's old history the current era in my opinion and we'll hear more about that in a few minutes Is that we biopsy these patients and we diagnose what this small renal mass is So we're very comfortable now with biopsy I was interested to see the voting on that Opportunity and every time I see that vote Say at annual intervals about double the proportion of the audience are responding that they're using biopsy and we know this is safe it does require a pretty skilled group of pathologists, imagers and others to interpret but at least 80 percent of these are going to be diagnostic and We're now on occasion doing what we call the B2 the second biopsy if we have a Non-diagnostic first biopsy in the same success rate so we get up in the high 90s now with these and we've learned that there are limitations that the tumors can understage Clinically can understage Pathologically at surgery there is an element of upgrading heterogeneity things that you know and oncocytic Cells remain problematic but Based on that we've looked at a cohort now of about 103 patients from our original group who had biopsies and we followed them albeit for relatively short time on average, but many of these long-term follow-up and We found that not surprisingly most still are a clear cell But that the these are patients by the way, they're biopsy cancers that there is about a quarter of them are papillary and really just slightly different from what you would see with a Nefrectomy series, so this this data has been quite interesting It's a relatively early on but here is a growth curve in red of clear cells which are growing and the Turquoise line are papillary tumors papillary type 1 tumors which don't grow so right off the bat There is a difference in the two biggest subsets of this population and if we look at bigger or smaller tumors the top line are presenting as larger than two centimeters growth rates roughly the same and We've looked at it from older and younger and we don't see a statistically significant difference Although there's a trend in older patients ironically to grow faster than the younger patients, so this is the meat of it. These are the growth rates Expressed as progression free survival or probability which is something we're all very familiar with and You can see in black that when a biopsy proven clear cell carcinoma has followed over time That by four years about half of them have progressed now Progression is going to be a somewhat arbitrary definition in this case It was rapid growth and or reaching four centimeters Whereas the top line are papillary tumors and you can see none of these patients have progressed and we have follow-up to eight years in a couple of these patients and when we look at it just simply in diameter that Is a fairly clear definition based on our staging you can see that the clear cells now expressed in red are also progressing as Different from the papillaries So that's the natural history that we see in these patients on surveillance by Specific tumor subtype now when we put that on the population who we are seeing with kidney cancer many of whom are older We know that there's a high rate of comorbidity a high rate of death from other causes in this population So just a couple of statistics there that people over 70 and I won't cite the references have a 30% chance These are people with Small renal masses have a 30% chance of dying of other causes If they have a greater than two Charleston comorbidity index the treatment does not appear to confer benefit and Patients that are over 75 and I think this is Rob Uso's Report have a greater chance of dying of other cancers than their kidney tumor and They have a much greater chance of dying of other non cancers So our conclusions at the present with a new small renal mass and I've used a superscript RCC to Indicate that it's been characterized by biopsy the papillaries as I said don't progress in the short term But more than half or at least half of the clear cells do Progress but slowly so we can personalize the management of these Patients and I think it's pretty clear now that we're on safe ground in the older population whether that's 70 or 75 to me 75 looks older than 70 and Obviously the infirm population if they are even if they are clear cell We might carry this to a younger set of patients in the papillary group and I think it's clear We can do initial act of surveillance in this population In all patients and we don't need to alter their lives or our lives to have earlier management And we have a greater window to preserve kidney function So that window of opportunity for partial nephrectomy for example, I think is much wider than we had appreciated previously now we Putting this in a cartoon. We've got a small tumor in a kidney that is more or less Healthy and I haven't touched on that there's a kidney on the other side and of course there's the host So we need to be complete in how we assess these patients a couple of Final comments. How do we follow these patients? There is no standard way to do this We try to use ultrasound as opposed to more expensive and potentially hazardous imaging technologies Particularly in this group where renal function isn't always Excellent and we tend to image them quite well, I think frequently at three and six months Initially just to get some sense of kinetics And if there's any uncertainty, we'll do it again at nine months, but we'll move quickly to annual Follow-ups our triggers for treatment though are poorly understood at this time and we tend to use size and Kinetics and the kinetics based on the evidence that where there has been Metastases and small renal masses that is they presented that way and went on to metastatic disease These seem to be in patients who have a rapid initial growth pattern And we do not have a good biologic marker at the present in urin or any form of virtual biopsy or the biopsy itself Which is a relatively small amount of tissue to work with lastly just this worry the Lack of a safety net for renal cell carcinoma. It's not like testicular cancer where we can quite comfortably Manage a patient who is at quite a high risk of metastases because we know we can salvage them In prostate and in kidney We don't have that safety net But it does appear to be very unusual for a patient to present with a small renal mass with a normal chest x-ray No other symptoms who goes on to metastasize under active surveillance And it's probably one to two percent at most and usually with initial active growth as a marker So thank you very much for allowing me just to overview and update this