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.
The Lancet. Oncology. 2024 Mar [Epub]
Shankar Siva, Mathias Bressel, Mark Sidhom, Swetha Sridharan, Ben G L Vanneste, Ryan Davey, Rebecca Montgomery, Jeremy Ruben, Farshad Foroudi, Braden Higgs, Charles Lin, Avi Raman, Nicholas Hardcastle, Michael S Hofman, Richard De Abreu Lourenco, Mark Shaw, Pascal Mancuso, Daniel Moon, Lih-Ming Wong, Nathan Lawrentschuk, Simon Wood, Nicholas R Brook, Tomas Kron, Jarad Martin, David Pryor, FASTRACK II Investigator Group
Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia. Electronic address: ., Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia., Department of Radiation Oncology, Liverpool Hospital, Liverpool, NSW, Australia; South West Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia., Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia., Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, Netherlands; Department of Human Structure and Repair, Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium., TransTasman Radiation Oncology Group, Waratah, NSW, Australia., Department of Radiation Oncology, Alfred Health Radiation Oncology, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, Australia., Department of Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Heidelberg, VIC, Australia., Department of Radiation Oncology, Royal Adelaide Hospital, South Australia, Australia; Department of Radiation Oncology, University of South Australia, Adelaide, SA, Australia., Department of Radiation Oncology, Royal Brisbane and Women's Hospital, QLD, Australia; University of Queensland, Brisbane, QLD, Australia., Department of Urology, John Hunter Hospital, Newcastle, NSW, Australia; The University of Newcastle, NSW, Australia., Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, NSW, Australia., Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Department of Urology, Liverpool Hospital, Liverpool, NSW, Australia., Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Royal Melbourne Clinical School, University of Melbourne, VIC, Australia., Department of Surgery, University of Melbourne, VIC, Australia; Department of Urology, St Vincent's Health, Melbourne, VIC, Australia., Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Department of Surgery, University of Melbourne, VIC, Australia., University of Queensland, Brisbane, QLD, Australia; Department of Urology and Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Department of Urology, Royal Adelaide Hospital, South Australia, Australia; Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia., Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia; The University of Newcastle, NSW, Australia., Department of Urology and Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; Queensland University of Technology, Brisbane, QLD, Australia.