Therapeutic Sequencing Strategies for Advanced Kidney Cancer - Episode 4

Newly Diagnosed Metastatic RCC: Frontline Therapy


Daniel George, MD: In this section, we’re going to talk about the treatment of metastatic newly diagnosed renal cell carcinoma. To start us off, Neeraj, let me go back to you. Tell us a little bit about how you risk-stratify patients who are coming in now with newly diagnosed metastatic disease.

Neeraj Agarwal, MD: Most commonly, we use IMDC risk criteria, and we include the 6 following variables in that risk stratification. These include presence of anemia, high neutrophil counts, high platelet counts, time of onset of metastases—how long it took to have metastases happen, more than 1 year or less than 1 year, from the original diagnosis of kidney cancer—performance status, and high calcium. Out of the 6 criteria, if somebody has none of them, we classify them as favorable-risk category patients. For patients with 1 or 2 of them, we call them intermediate-risk disease. Anybody will, with 3 or more of these, get categorized into the poor-risk category.

Nicholas J. Vogelzang, MD, FASCO, FACP: But remember, that 3 is not 6. A person with 3 is still pretty good and 2 are almost as good as 1. You’ve got to be a little bit of what I call Kentucky windage. You figure out how you’re going to aim the gun and hope you pick up the right curve on the gun. So, you’re not always worried too much about those subsets.

Daniel George, MD: I think that’s a good point in that this is a continuum. Let me ask you guys: Is there one factor, if you had to pick, that’s more important than some of the other ones or maybe more specific than some of the other ones?

Neeraj Agarwal, MD: I would say performance status is probably the most important for me.

Nicholas J. Vogelzang, MD, FASCO, FACP: Yes, I use anemia. If they’re anemic and they present with de novo metastatic disease, that’s not going to be good.

Daniel George, MD: I think it’s that time from nephrectomy to metastasis, particularly for the people who are 2 or 3 years out, even if they’ve got a little bit of anemia or something else. I’m less worried about that. It’s the patients who are really presenting with newly diagnosed disease and maybe have 1 or 2 other factors who I’m really nervous about. So, if I had to pick one thing for me, it is that timing, that natural history. It’s very, very specific to kidney cancer.

Nicholas J. Vogelzang, MD, FASCO, FACP: For the favorable-risk group, if they’ve had a nephrectomy 12 years ago and they’ve got 3 small lung nodules, those are people who most of us would watch, right?

Daniel George, MD: That’s right. I think it’s an excellent point. Is there a routine practice, if you will, for the subset of patients that you’ll really consider for active surveillance or deferred therapy and then follow? Bob, in your practice, how do you follow them?

Robert Alter, MD: The hardest conversation—when you have a referral from a urologist after the patient had a nephrectomy—is, despite small pulmonary nodules or minimal risk, do you say, “We’re going to watch you”? Having come to us anticipating a therapy, we’re saying, “Let’s redirect our goals.” Our goals here are long-term survival, not the immediacy of putting you on a therapy, which will at certain periods of time be chronic therapy. Once you start a therapy, you’re not really coming off therapy, right? Maybe immunotherapy may be a different discussion. It’s a reestablishment of the goals and then obviously we’ll get the risk factors.

I think that for patients with intermediate-risk small-cell lung disease, slow-growing disease—again, a lot of times we may see these patients for the first time having had their first scan—we have to take a step back, rescan them 2 or 3 months later, and see if their disease is changing or how they’re doing symptomatically. I don’t look at 1 factor that can predict how they’re going to do. You really have to use the whole categorization of the patient and put it together, and that requires more than 1 visit that can get you the gestalt about what these patients are going to do. They may evolve in front of you or they may just be a very slow grower. It just goes back to the conversation with them.

Daniel George, MD: Brad, you’re a little new to the field, but we’ve been doing metastasectomy for a while. Do you still do that at Dana-Farber? Are there still patients who you’ll consider for resection of metastatic disease?

Bradley McGregor, MD: Absolutely. If you have a patient who has all metastatic disease that you can render disease-free with surgery, specifically if they had a nephrectomy 5 years ago and a single lung lesion, those are patients we absolutely would talk about thoracic surgery and metastasectomy with. The hope is that you potentially achieve a cure, at a minimum, long-term disease control, and avoid unnecessary therapy for the patient.

Daniel George, MD: Neeraj, now we’ve got more options in surgery, right? SBRT is really picking up in our field—stereotactic body radiotherapy. How are you using that at your center?

Neeraj Agarwal, MD: There are always going to be some patients who are not surgical candidates. In the absence of high-level evidence for the use of radiation therapy and other energy-directed therapies, if you will, I would pick patients for those options only if they’re not surgical candidates.

Nicholas J. Vogelzang, MD, FASCO, FACP: For example, there are solitary bone metastasis. Those are patients who you may well use CyberKnife on. In fact, I think SWOG has been thinking about how to design a trial around oligometastatic renal cell carcinoma utilizing surgery or CyberKnife or approaches like that. I think for the very-good-risk patients, who you don’t want to jump on with toxic therapy, you want to have these options of surgery or CyberKnife or active surveillance.

Daniel George, MD: They go together, right? You can do 1 or mix or match. We’ve had patients for whom we’ve done this and then followed them for a period of time.

Robert Alter, MD: Exactly. If they have liver involvement, extensive bone involvement, or lymph-predominant disease, you anticipate that these patients are not going to be the ideal active surveillance patients. For those patients, you should be thinking about implementing some type of therapy. But I think, as Dr. Vogelzang is saying, the postponement of the first therapy with metastasectomies and SBRT, I want a patient who has time to heal, physically and mentally, with their new condition. Then we can postpone that initial therapy because we have no problem seeing patients every so often, but they enjoy not coming to our office.

Transcript Edited for Clarity