Considerations When Treating Newly Diagnosed mRCC

Daniel George, MD:When I see a patient with newly diagnosed metastatic kidney cancer, there are a few things that run through my head. The first is really around risk stratification of the disease. That is based upon patient factors and characteristics, as well as tumor factors and characteristics. These include things like the patient’s performance status, or functional status from symptoms, as well as laboratory values for things like anemia, thrombocytopenia, and neutropenia. These are all significant prognostic factors—thrombocytosis, and leukocytosis, as well as elevations in calcium, and the presence of multiple metastases.

I look at all of those factors and sort of weigh out where the patient falls within the risk stratification, if you will, of kidney cancer. It’s important to recognize that there are a lot of different models that we use, but they’re pretty much overlapping. I like the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) model because it’s based on factors that we mostly check in our everyday practice. Our metabolic panels, complete blood counts, physical exams, and our scans all give us the information to be able to apply that IDMC score to patients.

So, in the case of our 52-year-old gentleman who presented with his primary tumor in place and metastasis, he had some symptoms and he had some anemia associated with that. Those 2 factors make him an IMDC score of 2. That’s what we consider as intermediate-risk. If it’s 0 factors, it’s good risk. If it’s 1 to 2, it’s intermediate risk. If it’s 3 or more, we consider that poor risk. These are now based on independently validated model scores that correlate with overall survival in the era of targeted therapy. So, to me, that’s probably our most useful tool in assessing a patient like this.

The second part of assessing patients who are newly diagnosed with kidney cancer is really assessing the patient’s perspective. We talked about risk stratification and how that’s important. That’s primarily based on the patient’s functional status and a number of characteristics that have to do with the tumor. But, in the context of this, I also look at the patient as an individual. How old are they? What are their comorbidities? What’s their fitness like? You can have a performance status of 0, and still be relatively unfit. Or, you can have a performance status of 1, and be a very strong and fit individual. To me, fitness is really a factor that we haven’t taken into quantitative account, independent of functional status or performance status. But, I really see it as something slightly different.

It does factor in, along with age and comorbidity, when sizing up how a patient’s going to be able to tolerate our more aggressive therapies or combination therapies, versus therapies that are, perhaps, ones that aren’t as fully aggressive, or can be modified to a dose that’s tolerable. This is a big issue when we think about intravenous therapies, which, for the most part, are fixed-dose therapies. We give those doses and then they’re in. We can’t change them. Oral therapy really allows us to customize that therapy to the patient, with dose interruptions, dose modifications, and all kinds of dose regimens and breaks that really allow us to fine-tune that tolerance to what the patient can handle.

Another factor that I look at, when I’m sizing up the patient, is really the extent of the disease. So, there’s the risk stratification, but one of the things that our risk stratification doesn’t fully encompass is the burden of disease. I can see a patient who has intermediate-risk disease based upon 1 or 2 small metastases in 1 organ system, and that patient is actually pretty low volume. I can see another patient that maybe has had disease smoldering for a while, and lymph nodes or lung nodules. When you add them all up, it’s actually a fairly significant burden of disease that’s maybe gone on for years before we’ve treated them. So, the risk stratification and tumor burden are, again, not completely overlapping. I look at that as another kind of independent factor when I’m assessing these patients.

Transcript edited for clarity.

Case Scenario: A 52-year old male with mRCC

February 2018

• A 52-year old Caucasian man presented to his physician complaining of severe left-sided back pain
• Laboratory findings: mild anemia, otherwise WNL
• CT scan of the abdomen and pelvis showed a large left renal mass, several small lytic lesions in the lumbar and thoracic vertebrae, and a small pulmonary nodule
• The patient underwent cytoreductive nephrectomy
• Diagnosis; stage IV clear-cell renal cell carcinoma; good-risk
• He received radiation therapy to his spinal lesions and was then started on cabozantinib 60 mg daily
• The patient reported moderate nausea and vomiting and diarrhea after 6 weeks on therapy; he continues to do well with improved tolerance after dose adjustment to 40 mg
• Imaging at 3 months showed a significant decrease in size of the pulmonary nodule