Presentations. Renal Cell Cancer
Presentations; typically about half the patients will present with stage I or II disease. I think we are seeing more and more patients presenting with an incidental finding of renal cell carcinoma, because they are having CAT scans of the abdomen obtained for various reasons, and we are seeing patients in whom renal cell carcinomas are picked up incidentally on those scans. About one-quarter of the patients present with stage III disease and about one-quarter present with stage IV disease. Now Stauffer, in 1960-something, described a syndrome where patients with apparently disease isolated to the kidney presented with systemic constitutional symptoms and also liver function abnormalities. In this small series of seven patients, five of those patients presented with fever, six presented with weight loss, six presented with fatigue and 72% had all three; fever, fatigue and weight loss. This syndrome now I think is recognized to be due to cytokine production, possibly the production of IL-6. But in patients with liver function abnormalities but no evidence of metastases elsewhere, or certainly liver metastases, this complete syndrome can be successfully treated with surgery. And the liver function abnormalities will return to normal; fever, weight loss and fatigue will disappear upon resection of the kidney. So there are patients who present with systemic illness which you would sort of intuitively think had widespread metastatic disease, but those patients may well benefit considerably from a nephrectomy and may not need further treatment.
Now I mentioned briefly the sarcomatoid variant of renal cell carcinoma. Again, this is a variant of the clear cell type. Renal cell carcinoma itself is rare and of the renal cell carcinomas, only 5% or so represent sarcomatoid histology. So this is a rare tumor but I think it’s important to be aware of it. The cells have a sarcomatoid appearance and the way you can distinguish this tumor from a sarcoma of the kidney is that the sarcoma of the kidney will not have any clear cell features associated with it. It will be a pure sarcoma. The sarcomatoid variant will have some areas, maybe fairly small, but will have some areas that are typical of renal cell carcinoma, the more traditional cellular appearance. This is the survival curve for patients with sarcomatoid variant and this upper curve is the survival curve for patients with non-sarcomatoid variant. You can see that the sarcomatoid variant has a very dismal prognosis, median survival here being a number of months, just a few months. Another important point about sarcomatoid variant is that of the patients who presented with stage I-III disease - this is an article from M.D. Anderson, I think in the 80’s - where they reviewed 44 cases of sarcomatoid variant. They had 19 that presented with stage I-III disease and none of these patients were cured with nephrectomy alone. All of these patients relapsed. The two patients who were alive an in a durable complete remission were patients who relapsed and then were treated successfully with chemotherapy.
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There is a relationship between the proportion of the tumor that exhibits the sarcomatoid pattern. These two lines represent patients whose tumor was either 50% sarcomatoid and 50% regular renal cell carcinoma or greater, and then one of these lines is 75%. So when you have more than 50% of the tumor as a sarcomatoid histology you need to consider that patient as having a sarcomatoid histology. This line here was for patients who had less than 25% of the histologic specimen showing sarcomatoid variant.
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Now when patients develop metastatic disease, there’s a number of papers that have been written about how to assess their prognosis. And to be honest, these papers I think have been used primarily when pharmaceutical companies are trying to come up with a historical control group to compare for their studies, but they are useful to recognize. There’s really no surprises here. These are the major risk factors for poor prognosis and ECOG performance status, a poor ECOG performance status is a very significant risk factor. Time from diagnosis less than a year, two or more metastatic sites, prior cytotoxic chemotherapy and weight loss in the previous six months. These were data from 610 patients who were treated on Eastern Cooperative Oncology Group studies for renal cell carcinoma, and they were able to identify an algorithm that they felt helped differentiate the survival of these patients. But still the patients who had the best prognosis still only had a median survival of about 12 months. More recently in the Journal of Clinical Oncology this year another analysis was done looking at LDH, hemoglobin, calcium, the Karnofsky performance status and the prior nephrectomy were identified as risk factors in patients with metastatic disease, poor prognostic factors in patients with metastatic disease. These were the curves that they were able to generate, based on whether patients had no risk factors, one or two, three or more risk factors. So none of these things are surprising but it may help you in counseling your patients.
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