Stereotactic Body Radiotherapy for Renal Cell Carcinoma in Patients with Von Hippel–Lindau Disease—Results of a Prospective Trial

SIMPLE SUMMARY: Clear cell renal cell carcinoma (ccRCC) frequently occurs in patients with von Hippel–Lindau disease and is a leading cause of mortality in patients with this hereditary disorder. Partial nephrectomy, which is the standard treatment, is often complicated by multilocular tumor occurrence in both kidneys requiring repeated surgeries. Consequently, nephron-sparing resections become increasingly difficult ultimately leading to chronic kidney failure. In these patients or in patients who refuse surgery, alternative treatment approaches are needed. In this study, we investigated the outcome and toxicities especially for the kidney after stereotactic body radiotherapy (SBRT). We could demonstrate that SBRT in this highly vulnerable group of patients is feasible without any high-grade adverse events in the long-term and results in excellent local control at the site of treatment. Efficacy of SBRT is already proven for other anatomic sites and it could represent a valuable, non-invasive treatment option for ccRCC as well, especially for patients who are extremely vulnerable to any kidney injury. Further prospective trials evaluating SBRT for localized ccRCC are necessary to verify the promising findings and to examine its role as an alternative to surgery in inoperable patients. ABSTRACT: Von Hippel–Lindau disease (VHL) is a hereditary disorder associated with malignant tumors including clear cell renal cell carcinoma (ccRCC). Partial nephrectomy is complicated by multilocular tumor occurrence and a high recurrence rate. The aim of this study was to evaluate the potential of stereotactic body radiotherapy (SBRT) as an alternative treatment approach in VHL patients with multiple ccRCC. Patients with VHL and a diagnosis of ccRCC were enrolled. SBRT was conducted using five fractions of 10 Gy or eight fractions of 7.5 Gy. The primary endpoint was local control (LC). Secondary endpoints included alteration of renal function and adverse events. Seven patients with a total of eight treated lesions were enrolled. Median age was 44 years. Five patients exhibited multiple bilateral kidney cysts in addition to ccRCC. Three patients underwent at least one partial nephrectomy in the past. After a median follow-up of 43 months, 2-year LC was 100%, while 2-year CSS, 2-year PFS and 2-year OS was 100%, 85.7% and 85.7%, respectively. SBRT was very well tolerated with no acute or chronic toxicities grade ≥ 2. Mean estimated glomerular filtration rate (eGFR) at baseline was 83.7 ± 13.0 mL/min/1.73 m(2), which decreased to 76.6 ± 8.0 mL/min/1.73 m(2) after 1 year. Although the sample size was small, SBRT resulted in an excellent LC rate and was very well tolerated with preservation of kidney function in patients with multiple renal lesions and cysts.