Treatment Planning and Risk Assessment in mRCC

Robert Alter, MD: Risk assessment is something where we talk about the qualifications of a patient. I think our approach or how we see most of our patients and the results of the clinical trials represent how we conduct risk assessments. Most of our patients are going to have a risk that will either be a symptom of their disease, time from diagnosis to treatment, or a laboratory abnormality. With those risk assessments, we define these patients to be of intermediate risk. 

We now have a multitude of first-line options for patients. The risk assessment should be incorporated from the beginning. When we discuss how we take care of patients, conforming to our data from clinical trials and then applying them to what I see in my clinic, there is a very similar pattern when one practices. One anticipates the benefit and tolerability of systemic therapy.

Our patients do not receive cookie-cutter treatment. We do not believe that all therapies are the same, nor are all of our patients the same. I would endorse having patients enroll in clinical trials. I think there is a benefit about further selecting our patients, and that is going to be always important. We do not yet have a biomarker or a way of assessing which therapy is beneficial for patients.

The risk assessment models give us a clear-cut advantage when approaching our patients with not only first-line therapy but subsequent therapies as well.

When we approach our patients during consultations, the first visit is always the most impactful one. It is important to not only approach our patients regarding the new diagnosis and how we can take care of it, but we must also discuss the goals of therapy for a disease that has a moderate response in a dramatic fashion. Most of our patients will have a partial response. Our goals with therapies are to, of course, shoot higher.

Looking back at the usage of high-dose IL-2 [interleukin-2] and immunotherapy back in the 1990s—though small, less than 10%—complete remission seemed to be the ultimate goal. Patients who received high-dose IL-2 in clinical trials, in the data that analyzed this, even in the SELECT clinical trial, one was able to assess not only the patients who had complete remission, but also a good partial remission. The durability of these therapies is important as well. 

We must be idealistic and think about the complete remissions. We must think about the possibility that we may be able to have our patients receive therapy and then come off therapy, and actively monitor them. We still approach them with better tolerability in mind, as well as efficacy approaches that utilize agents including oral tyrosine kinase inhibitor therapies. 

We like to think about utilizing efficacious therapies with tolerability. The same approach applies to our immunotherapies. Toxicities can be so variable, yet we have to be aware of, again, taking care of a patient who has a cancer rather than the cancer itself. But we should remain idealistic when defining our treatment goals with the patient. 

We like to think about long-term overall survival; 25 years ago, using high-dose IL-2, survival was probably less than a year. Fast forward to what we have in 2020, going into 2021, our overall survival rate should be close to 5 years. Despite the fact that we are looking for scans to show regression or complete remission, sometimes we have to explain to a patient that no change or stable disease can still be a positive response. 

I described to a patient today how we put them on a certain therapy, and they were disappointed that the disease did not change. Yet, I explained to the patient that, “For the last 6 months, your disease was growing steadily each month. And now suddenly, on therapy, your disease is not growing at all.” That defines a change. 

We try to have these conversations with patients early. We must allow patients to understand that our goals are the same as their goals: elimination of the disease with excellent quality of life. We should have a conversation about overall survival, but we should definitely try to have a conversation about complete remissions as well.

Transcript edited for clarity.