Prospective Trials Could Refine Potential Roles for Radiation in Advanced RCC

Although radiation has not been historically used for the treatment of advanced renal cell carcinoma (RCC), metastasis-directed radiation could help defer or supplement systemic therapy in certain patients, according to Chad Tang, MD.

In a presentation at the 2024 ESMO Congress, Tang delved into the background of radiation therapy in the treatment of RCC, noting that improvements in techniques have helped make this modality an option in certain circumstances.

“It's important for the medical oncologists to be open to discussing cases with their radiation oncologists because I believe the general consensus is that radiation isn't effective for RCC. However, I think that is changing,” Tang said.

In an interview with OncLive^®, Tang discussed historical data for radiation in the treatment of patients with RCC, highlighted areas where radiation could serve a role, and detailed ongoing studies examining radiation in RCC.

Tang is an associate professor in the Department of Radiation Oncology, Department of Translational Molecular Pathology, and Department of Investigational Cancer Therapeutics in the Division of Radiation Oncology, and an assistant professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston.

OncLive: At the 2024 ESMO Congress, you presented on the role of radiation in advanced RCC. What was the goal of this talk?

Tang: My presentation was divided into 3 parts. In the first part, I explained the background of why radiation therapy was not used for RCC, [spotlighting] some old data, looking at the sensitivity of radiation therapy in RCC, and [examining] older trials looking at lower doses of radiation and their adverse effects [AEs]. Then, I talked about the newer techniques that we're using and strategies in which we're employing radiation to defer starting systemic therapy, which we believe is beneficial to patients from a toxicity standpoint, quality of life standpoint, and from a health care system cost standpoint.

Then I talked about a number of different areas in which we're using radiation therapy to supplement systemic therapy, such as in patients with oligoprogression, where we're using radiation in a limited number of sites when patients are progressing and keeping them on the same systemic therapy. [I also talked about how radiation could be used] in the treatment of the primary [tumor] or in patients with varying histologies of RCC.

How is radiation therapy currently utilized in the RCC treatment paradigm?

Right now, radiation therapy is most often applied as stereotactic body radiation therapy [SBRT], which [involves] high doses in a short number of fractionations. [SBRT] can be used in both primary RCC to control [the tumor] instead of nephrectomy, or it can be used as a means to control a more indolent, metastatic RCC when only a few sites of disease anatomically appear or progress.

Other areas where [radiation] can be used are as palliative treatment, which has been a mainstay of radiation therapy for metastatic carcinomas. These include things such as bone metastases, brain tumors, or—what we've been doing more of—inferior vena caval thrombosis. Those are some of the general areas where we use radiation and how we use it.

What are some challenges associated with integrating radiation therapy into RCC management?

RCC drug development is constantly evolving. There are [always] new agents coming on board. The newest, for instance, is belzutifan [Welireg], which we're seeing a lot more. The question [then involves] how to integrate that sequentially with radiation therapy [in patients with], for example, a bone metastasis that is progressing or a single progressive site. It sometimes takes years for toxicities to develop after radiation therapy. We don't have the data right now for these newer agents to know [exactly] how to integrate systemic therapy and radiation. That's one big area.

Are there any other questions that remain regarding the role of radiation therapy in RCC?

Several trials are investigating up-front radiation therapy or sequenced radiation therapy to the primary site of disease in the kidney in patients who have metastatic disease. There are at least 3 trials that I'm aware of that are looking at this, [including] the phase 2 CYTOSHRINK trial [NCT04090710] run out of Canada, the phase 2 SAMURAI study [NCT05327686] in the United States, and a new Italian study called ITALIC-RCC [EudraCT 2024-517789-41-00], which just opened recently. [Up-front radiation] is an area of interest because, unlike surgery, there's a lot less recovery and time off systemic therapy with radiation-based techniques.

Other interesting areas [involve] radiation therapy instead of systemic therapy in some patients with more indolent, oligometastatic RCC. The phase 3 SOAR trial [NCT05863351] opened up, where investigators are randomly assigning patients [with RCC with limited metastases] to a radiation-based strategy vs standard of care [systemic therapy].

We have another trial called the phase 2 ASTROs study [NCT06004336] where I am the principal investigator, and we are looking at adjuvant pembrolizumab [Keytruda] after radiation therapy for oligometastatic disease.

How can medical oncologists and radiation oncologists work together to advance RCC management?

We're educating the radiation oncologists on our side, and medical oncologists should [consider] radiation for more cases. [Radiation could help] extend systemic therapy or offer some time off systemic therapy. Open dialogues have helped us treat patients and develop these questions. That's always encouraged.

Disclosures: Dr Tang reported grant funding/trial support from CPRIT, NCCN, Department of Defense, Merck, Myriad; advisory boards/honorarium/travel from Bayer, Diffusion Pharmaceuticals, Siemens Healthineers, Lantheus, Telix, Boston Scientific, Molli Surgical, Vision RT; and royalties including Editor of MD Anderson Handbook of Radiation Oncology, published by Wolter Kluwer.

Reference

Tang C. Is there a role for radiation in advanced RCC? Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain.