Ultra-hypofractionated stereotactic ablative body radiotherapy for primary renal cell carcinoma: 5-year outcomes from a pooled analysis of the FASTRACK trials
Menée à l'aide des données de 2 essais cliniques (FASTRACK et FASTRACK II) incluant 108 patients atteints d'un carcinome rénal de grande taille et inéligibles au traitement chirurgical (durée médiane de suivi : 5 ans ; âge médian : 76,9 ans ; 28 % de femmes), cette étude analyse l'efficacité, du point de vue du contrôle local, d'une radiothérapie stéréotaxique d'ablation ultrahypofractionnée
Background: Stereotactic ablative body radiotherapy (SABR) is a non-invasive therapy for inoperable primary renal cell carcinoma. However, long-term prospective clinical trial data are scarce. We aimed to use pooled data from two clinical trials (FASTRACK and FASTRACK II) to evaluate activity and safety of SABR in the long term.
Methods: In this pooled analysis, we used data from FASTRACK, a single-institutional, phase 1, prospective clinical trial conducted at the Peter MacCallum Cancer Centre (Melbourne, VIC, Australia), and FASTRACK II, an international, non-randomised, phase 2 clinical trial conducted in seven academic hospitals in Australia and one in the Netherlands. The treatment protocol, inclusion and exclusion criteria, and dose constraints were the same in both trials. Patients had primary renal cell carcinoma and were deemed medically inoperable or high-risk for surgery, were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 2 or less, tumours of 10 cm or less in maximal dimension, and N0–N1 disease. Tumours 4 cm or smaller in FASTRACK II and smaller than 5 cm in FASTRACK received a single fraction of 26 Gy and larger tumours received 42 Gy in three fractions 48 h apart. Local control (freedom from local progression) was the primary endpoint, assessed using Response Evaluation Criteria in Solid Tumours (version 1.1) criteria. The analyses were conducted only in patients who commenced protocol treatment. Safety was evaluated with the Common Terminology Criteria for Adverse Events in participants who started protocol treatment. A patient representative was involved in the study design and conduct of FASTRACK II. Both trials were registered with ClinicalTrials.gov (FASTRACK: NCT01676428; FASTRACK II: NCT02613819) and are both completed.
Findings: 108 patients were enrolled between June 28, 2012, and Oct 17, 2014 (FASTRACK), and between July 28, 2016, and Feb 27, 2020 (FASTRACK II). Five patients did not receive treatment (one opted for surgery, three did not meet dose constraints and were withdrawn, and one died before treatment). Median age was 76·9 years (IQR 70·0–81·9). 74 (72%) of 103 patients analysed were male and 29 (28%) were female. Race and ethnicity data were not collected. The median follow-up was 5·0 years (IQR 2·3–6·0). Local control at 1 year was 100%, at 3 years was 98% (89–100), and at 5 years was 98% (89–100), with local progression occurring in only one patient who had both local and distant progression at 28 months. Eight (8%) patients had grade 3 adverse events: abdominal or flank pain (four [4%] patients), nausea or vomiting (two [2%]), colonic obstruction (two [2%]), fatigue (one [1%]), and colitis or diarrhoea (one [1%]). All grade 3 or worse adverse events occurred within 2 years of SABR delivery. No grade 4 adverse events or treatment-related deaths were reported.
Interpretation: This pooled analysis from two clinical trials of SABR in patients with larger primary kidney tumours unsuitable for surgery supports evidence of long-term local control and low rate of severe adverse events. These results support further investigation through a randomised trial comparing SABR with surgery in select operable patients.
The Lancet Oncology , résumé, 2026