Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial.
This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0–2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual.
Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70–82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7–5·5). All patients enrolled had T1–T2a and N0–N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38–60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred.
To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer.
Cancer Australia Priority-driven Collaborative Cancer Research Scheme.
This is a phase II trial conducted in Australia and the Netherlands investigating 70 patients with biopsy confirmed renal cell carcinoma, who were medically inoperable or high risk for surgery. Median age was 77 years, median Charlson comorbidity index 7, median BMI 32 kg/m2, median tumour size 4.6 cm, the median RENAL score was 8. Tumours up to 4 cm received 26Gy and up to 10 cm 46 Gy in three fractions. The median follow-up was 43 months. Treatment resulted in local control at 12 months in 100% (p<0.0001). Cancer-specific survival was also 100%. Freedom from distant failure at 12 months and 36 months from treatment commencement was 97% (95% CI 89–99). Overall survival was 99% (95% CI 90–100) at 12 months and 82% (70–89) at 36 months from treatment commencement. Baseline mean eGFR was 61.1 mL/min per 1.73 m2 and changed at 24 months from treatment commencement, by –14.6 mL/min per 1.73 m2. Split function for the ipsilateral kidney at baseline was 50% and at 24 months 33%. 10% of 70 patients sustained one or more grade 3 treatment-related adverse events.
This is a very first single-arm prospective trial assessing SBRT in primary renal cancer in inoperable patients. Short-term local control and survival outcomes are excellent with low toxicity rates for which the authors could be congratulated.
Currently, established curative treatment for T1a renal cancer is surgery, with alternative of ablation or surveillance for patients who are not fit for surgical therapy. For larger than 4 cm tumours, ablation loses its efficacy whereas SBRT has demonstrated its efficacy in 43 months follow-up in tumours measuring >4 cm in this trial. However, it is noteworthy that in medically inoperable patients, especially over 75 years with high Charlson co-morbidity index and poor ECOG performance status, other-cause mortality exceeds cancer specific mortality (1) and in active surveillance trials 1.0% died from RCC and 23% died from any cause (2). Therefore, we do not know whether in this patient cohort SBRT is superior to surveillance alone in comparative survival figures. Nevertheless, this trial is pivotal in the field by demonstrating efficacy of SBRT in RCC with median follow-up of 43 months and it created several questions targeting various knowledge gaps: would SBRT be superior to watchful waiting in inoperable patients? Do these patients have longer progression free survival, which will extend their quality of life years without need for systemic therapy? In addition, it challenges the surgical community, how to improve morbidity and safety in surgical treatment and anaesthesia or would novel non-invasive SBRT offer a competitive treatment option also to younger patients who have long life-expectancy? The authors are highly encouraged to set up the randomised controlled trial to answer some of these questions.
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