SUO 2019: The Role of Radiation in the Management of Renal Cell Carcinoma

Washington, DC ( Dr. Vitaly Margulis presented on the role of radiation in the management of renal cell carcinoma (RCC). He began his talk by dispelling the widespread belief that RCC is radio-insensitive. While, at conventional lower doses of radiation the cancer cells are immune, with the high doses feasible with Stereotactic Ablative Radiotherapy (SAbR), he demonstrated that RCC is actually very sensitive. SAbR, also referred to as SBRT, has the ability to provide very focused and precise radiation, allowing for high dose delivery with a minimized effect on surrounding tissues. The remainder of his talk focused on the role of radiotherapy in the primary, locally advanced and metastatic settings.

To begin, Dr. Margulis focused on the application of radiation to localized renal cell carcinoma. First, he outlined appropriate patient selection, limiting this technology to those that have biopsy proven malignancy which is growing at a rate greater than 0.4 cm per year. In the UTSW experience, they have found that radiation controls 93% of localized cases, with metanalyses demonstrating similar efficacy with response rates in the 80-90% range. Effective treatment requires a dose equivalent greater than 10Gy x3. However, even at these doses, toxicity is minimal with the average decline in renal function being 7ml/min/1.73m2.

For patients with locally advanced disease, his group has found that SAbR was effective at curbing disease growth, particularly in non-operative candidates. These initial experiences were hypothesis-generating for the role of radiation in the management of the IVC tumor thrombus. Specifically, he questioned whether or not SAbR could sterilize a tumor thrombus to reduce the rate of post-surgical metastases. Currently, only a little over half of patients are free of progression at 1 year (55% 1-year PFS). To that end, they are enrolling participants in a safety lead-in phase II trial to evaluate the safety and efficacy of neoadjuvant SAbR. In May, the safety data was presented at the AUA, overall demonstrating a low toxicity profile with only grade I adverse events. Since then, the interim analysis revealed an 83% 1- year PFS in the cohort available for review. However, 21 patients are still required for enrollment and final data is maturing. (NCT02473536)

Next, Dr. Margulis explored the role of SAbR in the management of metastatic disease. In well-selected patients, metastasectomy has been shown to provide oncologic benefits. Similarly, studies have reported local control rates between 87%-97% following SAbR. Predictors of response included non-osseous metastases, not being exposed to more than 1 line of systemic therapy, M0 at presentation and favorable risk group. Moreover, Dr. Margulis shared two cases from their cohort that had regression of metastases following SAbR of the primary renal mass without the receipt of systemic therapy.

Specifically, looking at oligometastatic disease, individuals with less than 3 metastatic sites, he described an over 90% local control rate and a significant improvement in freedom from systemic therapy. Given these initial results, in partnership with radiation oncology, they have developed a phase II trial to provide this treatment on a protocol to formally evaluate PFS and freedom from systemic therapy. They are currently recruiting patients, with an accrual goal of 48 participants. (NCT02956798) Additionally, he discussed another trial for oligoprogressive disease, with early results demonstrating a 9-month postponement of additional therapy. (NCT03696277)

Looking to the future, Dr. Margulis discussed the potential of SAbR to prime the patient for subsequent immunotherapy. He shared their RADVAX trial, a two-stage study designed to allow for evaluation of safety and initial efficacy which is currently enrolling. (NCT03065179)

In summary, the session highlighted a growing interest in SAbR for RCC given the plethora of ongoing trials within this field. With many of these trials maturing over the next few years, the role of SAbR in the management of RCC representing an exciting, evolving space.

Presented by: Vitaly Margulis, MD, Professor of Urology, UT Southwestern Medical Center, Dallas, Texas 

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC

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