This Phase II Prospective, parallel and open-label randomised control trial will investigate whether a radiotherapy technique (called SABR) can treat early stage liver cancer more effectively than current treatments which use heating probes directly inserted into the tumour or chemotherapy or radioactive particles injected into the blood supply of the tumour. Investigators hypothesize SABR will result in higher rates of freedom from local progression (FFLP) at 2 years compared to percutaneous thermal ablation ± TACE or transarterial therapies (TACE/TARE).The study will also look at other important outcomes such as progression free survival, overall survival, side effects, quality of life and people's experiences of their treatment.

The SOCRATES randomised controlled trial will assess the efficacy, toxicity, HRQoL profile and cost effectiveness of SABR compared to the current SOC treatment in patients with first diagnosis of unresectable, single nodule HCC. Participants will be placed into one of two groups based on the size of their tumour and whether thermal ablation is an appropriate treatment for them. The study will include about 218 participants in total. Participants will be randomly assigned to receive either SABR or the current standard of care. Standard care may include thermal ablation, transarterial chemoembolisation (TACE), or transarterial radioembolisation (TARE).

Inclusion Criteria:

1) Histological or radiological diagnosis of single, new HCC with largest diameter =8 cm (BCLC stage 0 or A).

• a) If prior history of HCC, the prior HCC must have been:
• Early stage, solitary HCC, =5 cm in size and,
• Have arisen within a different liver segment to the current HCC and,
• Treated with curative intent therapy >2 years prior with no evidence of active disease at the site.
• 2) As per local multidisciplinary HCC meeting consensus patient is suitable for percutaneous thermal ablation and/or transarterial therapies and not suitable for or declined liver resection and not planned for liver transplantation.
• 3) Child-Pugh score =B7* with no or diuretic-controlled ascites
• 4) ECOG performance status =2
• 5) Platelets =50x109/L, Haemoglobin =80 g/L, Neutrophils =1.0x109/L, INR <1.8 (except if on therapeutic anticoagulation)
• 6) 18 years of age or older and able to provide written consent

Exclusion Criteria:

• 1) Presence of multifocal HCC, macrovascular invasion or extrahepatic disease
• 2) Prior treatment for any HCC within last 2 years.
• 3) Clinically evident ascites or hepatic encephalopathy
• 4) Prior abdominal radiation therapy that would preclude the delivery of protocol defined SABR to the tumour.
• 5) Untreated Hepatitis B or C
• 6) Known additional invasive malignancy (excluding non-melanoma skin cancer) that is progressing or required treatment within the last 2 years.
• 7) Pregnancy