Clinicians are taught that renal cell carcinoma is radioresistant, but modalities such as stereotactic body radiation therapy (SBRT) can be safe and efficacious in certain patients with RCC. In this interview, Vitaly Margulis, MD, of UT Southwestern Medical Center, Dallas, outlines the advantages of SBRT and offers a preview of the RADVAX trial, which combines radiotherapy and immunotherapy.
Compared with other types of cancer, how resistant is renal cell carcinoma to radiation therapy?
Historically, we are taught that renal cell carcinoma is radioresistant, and this is certainly what I learned when I was going through my training. The reality is that kidney cancer is actually quite radiosensitive; it's just that you have to deliver a higher radiation dose. Techniques like stereotactic body radiation deliver radiation in fewer fractions but at higher doses, and kidney cancer actually responds very well to those types of treatments.
How is stereotactic body radiation therapy currently used in the treatment of RCC?
There are several indications that are important to mention for how SBRT is used in kidney cancer. For patients with a primary tumor, one clinical dilemma that we as urologists face are those with a large amount of small renal masses; most of them are indolent and don't need to be treated, but some grow rapidly. The idea for SBRT in this setting is to convert a growing renal mass to a renal mass that stabilizes and doesn't grow and can be absorbed safely.
Especially when you factor in the older patient population, we want to try to avoid any invasive procedure, and SBRT technology is attractive because the radiation can be delivered in fewer fractions, so there's not a big time commitment on the patient's part. It’s also safe, it's not invasive, there's no need for anesthesia, and it's an outpatient treatment. It's very attractive, and I think we will see more and more utilization of this in the treatment of the primary tumor.
With locally advanced disease, in investigational settings, we actually radiate the thrombus to sterilize it. When we go to do the surgery, there's a lot of manipulation involved and a lot of cancer cells get released into circulation, so the idea is to give radiotherapy before that to sterilize those cells and prevent them from implanting. In an ongoing clinical trial looking at this, preliminary data show that it seems to be safe to utilize this approach, and it also may be very efficacious.
Kidney cancer metastasis can be quite symptomatic, and SBRT is a great way to relieve patient suffering and pain. Another role for SBRT in this setting is for patients who are progressing on systemic therapy. We have multiple lines of systemic therapy for kidney cancer. In a lot of cases, patients mostly respond but have one or two sites that are not responding and are progressing. If you can radiate those sites, you can delay change of systemic therapy. There are only so many lines of therapy that these patients can get. If we keep switching very quickly, we run out of options, so we utilize this as part of a clinical protocol to delay the need to change systemic therapy. That's a very attractive strategy to prolong patient exposure to some of these treatments.
What does the future hold, and how does the RADVAX trial fit in?
Another role of radiotherapy is basically to create an in situ vaccine. In some instances, kidney cancer prevents our own immune system from infiltrating and developing a response. The way to attack that phenomenon, and what the RADVAX trial brings to the table, is to radiate one of the metastatic sites, which releases a lot of antigens into circulation. So some of the things that the immune system was not seeing and was not activated by are now released into circulation. That's the radiation component.
The second component is immunotherapy. You combine this antigenic release with drugs that can get the primary immune system to respond to those antigens. That's the idea behind the RADVAX trial—a combination of SBRT and immunotherapy. The RADVAX trial has fully accrued at UT Southwestern with 25 patients. Data will be presented at the upcoming Genitourinary Cancers Symposium. Although I am not at liberty to discuss the results, I can say that the preliminary data are very encouraging.
What are your take-home messages for urologists regarding SBRT and RCC?
SBRT is very effective for several kidney cancer patient-related issues. First, it's an excellent way to palliate pain. Second, it's a good way to stabilize somebody's disease in a minimally invasive or noninvasive manner. It's not a replacement for standard of care surgeries, systemic therapies, and ablation therapies, but it needs to be part of the armamentarium that we offer to our patients routinely.