Stereotactic Body Radiotherapy for Kidney Cancer: Ready for Prime Time? - Beyond the Abstract

In this paper, we have aimed to describe the role of stereotactic body radiotherapy (SBRT) in renal cell cancer (RCC). To this end, we have performed a search of prospective and retrospective studies and have reviewed clinical guidelines and ongoing clinical trials.

RCC represents 85% of nephrological tumors and 4% of new cancer diagnoses. Surgical resection is the main treatment for localized disease and can also be useful in advanced stages as cytoreduction prior to systemic therapy. Conventional external beam radiotherapy with curative intent has experienced a decline over the last decades and has been excluded from international clinical guidelines on RCC, mainly due to the radioresistance of these tumors, among other reasons. Nonetheless, radiotherapy has a palliative role in metastatic disease to reduce pain and improve quality of life.

The technological evolution in the field of radiotherapy has allowed for the administration of higher doses in few fractions, offering a non-invasive ablative treatment that has reported notable local control rates both in primary tumors and metastases in various sites, all of this with low morbidity. Moreover, in vitro studies have shown that these high doses can overcome the intrinsic radiosensitivity of RCC, with SBRT also possessing potential immunostimulatory effects which could improve disease control in this highly immunogenic tumor. In this context, RCC patients with localized disease that refuse or are not surgical candidates can benefit from SBRT, as well as patients with oligometastatic disease.

In the case of SBRT for primary RCC, the main indications include bilateral renal involvement, chronic kidney disease, and patients with a single kidney. It can be safely administered in large tumors and fragile patients.

The retrospective evidence available comprises a heterogeneous group of studies with a limited number of patients. A study by Siva et al. from 2018 included 223 patients treated with SBRT for RCC, reporting a two and four-year local control of 97.8%, and two and four-year overall survival of 82.1% and 70.7%, respectively. The International Radiosurgery Oncology Consortium for Kidney (IROCK) published a study in 2020 that included 95 patients with RCC larger than 4 cm treated with SBRT. With a median follow-up of 2.7 years, overall survival was 83.7% and 69.2% at two and four years, respectively, with a local recurrence rate at four years of 2.9%.

Prospective evidence is limited and mainly comes from phase I and II studies that evaluate safety and treatment efficacy. The studies analyzed in this review report low rates of acute toxicity with a manageable decrease in glomerular filtration rate, and favorable local control data.

In the management of primary RCC, cryotherapy and radiofrequency ablation are limited by location and tumor size and are invasive techniques. SBRT allows for the treatment of larger tumors or those located centrally or in the proximity of vascular structures or the ureter. A 2020 study comparing different local techniques in terms of overall survival showed 88% for partial nephrectomy, 84% for cryoablation, 87% for radiofrequency/microwave ablation, and 77% for SBRT at three years. Five-year overall survival was 84%, 77%, 76%, and 58%, respectively. To note, SBRT included fewer patients with larger lesions.

A subgroup of patients that are going to present a limited number of metastases, usually five or fewer (oligometastatic disease) may benefit from local ablative treatment to delay the start of systemic therapy, prolong disease-free survival, and potentially cure the disease in certain cases. SBRT is a safe and effective technique in this setting, with local control of 90% and grade ≥ 3 of 1% according to a recent meta-analysis (SABR ORCA) published by Zaorsky. There are several retrospective and some prospective studies that show the efficacy of SBRT in oligometastatic patients, although there is great heterogeneity in terms of the number and location of the treated lesions, total dose, and fractionation.

In short, SBRT is a promising strategy for the management of patients with localized or oligometastatic RCC that is already included in the main clinical guidelines. It is a safe and effective technique that has a favorable toxicity profile and preserves renal function. Further prospective studies are warranted to identify the subgroups of patients that can benefit the most from ablative treatment to the primary tumor and/or metastatic sites, either exclusively or in combination with other therapies

Written by: Eliseo Carrasco Esteban, Department of Radiation Oncology, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain

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