Initial Therapy for Advanced Renal Cell Carcinoma - Episode 4
Elizabeth R. Plimack, MD: The IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk criteria were developed at a time when we mostly were leaning on VEGF inhibitors to treat kidney cancer. And it’s a very simple set of 6 criteria—4 blood results and 2 clinical parameters—that can, if you assess them for a given patient, really predict their prognosis. Favorable-risk patients will do very well, intermediate-risk patients do intermediately, and poor-risk patients have a poor prognosis. And so, these were really developed just as a prognostic tool.
Then we started to leverage them in the design of clinical trials with immunotherapy. And we learned that immunotherapy actually works best, ironically, in patients with poor and intermediate risk. And VEGF inhibitor therapy may work just as well or better in patients with favorable-risk renal cell carcinoma. In the recent guidelines that various groups have put together, treatment recommendations in the frontline setting do hinge on the patient’s IMDC risk criteria. And that’s based on the effect of risk on overall survival in large randomized trials.
Eric A. Jonasch, MD: When looking at the contemporary and currently used risk stratification algorithms that we employ in renal cell carcinoma, the IMDC criteria and the Memorial Sloan Kettering Cancer Center criteria [MSKCCC], they have 4 features in common, which are time from diagnosis to treatment, anemia, hypercalcemia, and performance status. And these probably are the most important core features in these algorithms and help us define patient risk. Now that doesn’t mean that the LDH [lactate dehydrogenase] elevation or the high white blood cell count or the high platelet count that are seen in the MSKCCC or the IMDC criteria, respectively, aren’t useful. It’s just that in the analyses that were performed with one versus the other, those either fell in or fell out. But I think the message here is that we have some pretty clear clinical parameters and laboratory parameters that can help us decide on the underlying biology of these patients and which treatment then to use.
Elizabeth R. Plimack, MD: Favorable-risk renal cell carcinoma is the most interesting category. First of all, it’s the minority of patients who are favorable risk. Only 10% to 15% will fit this category. Secondly, it’s really a category limited to patients with indolent or slow-growing disease because typically, patients with favorable-risk disease had their kidney removed with curative intent and then years later grew a metastasis, such that their interval from diagnosis or surgery to treatment was greater than a year. The other way you can meet those criteria is if you have this slow-growing, indolent disease and you’re on observation.
Right off the bat, regarding that 1 criterion, you have to meet it to be defined as favorable risk. You have to meet all the criteria to be defined as favorable risk. It describes a slow growth pattern. They have, by definition, a slow biology. The other blood tests are used in conjunction with that, and I don’t really hedge on any of those factors. So, if there’s a patient who had their kidney cancer removed 5 years ago and it has recurred late, yes, that’s an indolent growth pattern. But if they have an abnormal laboratory value in any of the 4 parameters that we use for IMDC, they’re still at least at intermediate risk. I go by the book when I assess risk.
Eric A. Jonasch, MD: In 2020, we don’t have a really good way of mechanistically or biologically defining features that define good- or intermediate- or poor-risk patients. We have the IMDC and MSKCC criteria, which help guide us. But with regard to linking, for example, good risk to some of the genomic features like PBRM1 mutations or SETD2 and backbone mutations, we’re less good at doing that.
I think we’re going to see an evolution toward a linking of molecular features to these clinical pathological features. But we’re not quite there yet. I would say that one of the key things we’re going to be doing over the next couple of years is coming up with more robust genomic and biological correlates to these clinical and laboratory correlates that we’re using.
Elizabeth R. Plimack, MD: Goals of therapy are a really important thing to address up front with a patient early in their diagnosis because every decision you make about treatment really hinges on a shared understanding of what the goal is. For all patients with advanced kidney cancer, the goal is to keep them around as long as possible and feeling as well as possible and out there living their life with this disease. We do what we can to control it with medications, but the goal is always their quality of life and length of life.
When we say it like that and when we admit we can’t cure them, that focuses patients on the really important pieces of their treatment. They become more comfortable with taking treatment breaks for vacations, which we think is important. Some may become more comfortable with the observation approach when we frame it that way. I think the goals of care don’t really change with risk, it’s just the prognosis that changes. And what we’re seeing is with immunotherapy-based combinations, we may be able to bend that prognosis for poor- and intermediate-risk patients, as these drugs tend to be more effective in that group of people. In summary, I would say the goals of care don’t change based on IMDC risk, but the expectations and the outcomes and long-term nature of treatment may be different.
Transcript Edited for Clarity