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Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS)

  • Shankar Siva,
  • Alexander V Louie,
  • Rupesh Kotecha,
  • Melissa N Barber,
  • Muhammad Ali,
  • Zhenwei Zhang,
  • Matthias Guckenberger,
  • Mi-Sook Kim,
  • Marta Scorsetti,
  • Alison C Tree,
  • Ben J Slotman,
  • Arjun Sahgal,
  • Simon S Lo

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0–100), 5-year progression-free survival was 80·5% (95% CI 72–92), and 5-year overall survival was 77·2% (95% CI 65–89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25–26 Gy in one fraction, or 42–48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.

Commentary by Dr. Teele Kuusk

This systematic review evaluated stereotactic body radiotherapy (SBRT) in local renal cell carcinoma for patients whose tumour is inoperable, technically high risk, or who decline surgery. Thirty-six studies were included. The weighted median follow-up was 31.2 months, and the weighted median maximum tumour size was 4.4 cm. The median weighted baseline estimated glomerular filtration rate was 55 mL/min (range 28.7–82). Median reported local control rates were 94.1% (range 70.0–100). 5-year median PFS was 80.5% (95% CI 0.72–0.92) and the median overall survival (OS) was 77.2% (95% CI 0.65–0.89%). 3.9% patients underwent post-treatment dialysis. Treatment-related toxicities at grade 2 intensity were reported in 5.3%, grade 3-4 in 3.4%. The authors addressed that the optimal dose was 25–26 Gy in one fraction, or 42–48 Gy in three fractions for larger tumours. Post-treatment biopsy is not predictive for outcome and therefore is not recommended. SBRT for solitary kidney is safe and effective. For follow-up, cross-sectional imaging of abdomen and chest is recommended biannually.

SBRT presents a highly appealing treatment modality for kidney cancer due to its non-invasive and non-toxic characteristics. However, certain concerns remain that necessitate attention. Firstly, the median surveillance period in the trials is less than 3 years, leaving uncertainty regarding whether SBRT yields a long-term curative outcome. Trials incorporating post-treatment biopsies revealed a high incidence of viable tumour cells even after 9 months. Nevertheless, 1-year biopsy data indicated a terminal differentiation state, suggesting that the observation of cell death after SBRT may require a more extended timeframe.

Furthermore, the long-term impact on adjacent organs remains unclear, and there is a lack of information regarding the extended-term outcomes of renal function.

Exploring potential differences between poor and good-risk cancers could be insightful to ascertain whether SBRT demonstrates similar outcomes within these subgroups. Despite these considerations, commendation is due to the International Stereotactic Radiosurgery Society (ISRS) for their efforts. Furthermore, the integration of various treatment modalities, including medical treatment, could be an area of interest for future trials. It is important to note that the current limitation of the small number of patients hinders the ability to draw high-level conclusions, and the anticipation of larger randomised comparative trials involving surgery and ablation is keenly awaited.