Table 2. Risk of bias assessment.

Domain	RADICALS-RT (5)	GETUG-AFU-17(6)	RAVES(7)
1. Risk of bias arising from the randomisation process	Low risk Was allocation sequence random? YES, minimisation with stratification by Gleason sum score, margin status, RT schedule and study centre. Was allocation sequence concealed? YES, central randomisation at the MRC Clinical Trials Unit at UCL using a computer-implemented algorithm Did baseline differences suggest a problem? NO, arms are well balanced	Low risk Was allocation sequence random? YES, minimisation with stratification by study centre, pT stage and Gleason grade to avoid significant imbalances between the arms Was allocation sequence concealed? YES, central randomisation using an internet based service, or via central randomisation at the Institut Bergonié Did baseline differences suggest a problem? NO, arms are well balanced	Low risk Was allocation sequence random? YES, minimisation algorithm. Patients are stratified by pre-operative PSA; Gleason score; margin positivity; seminal vesicle involvement; and radiotherapy institution Was allocation sequence concealed? YES, internet based randomisation system Did baseline differences suggest a problem? NO, arms are well balanced
2. Risk of bias due to deviations from the intended interventions	Low risk Were participants aware of their assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were carers and people delivering the interventions aware of participants’ assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were there deviations from the intended intervention that arose because of the trial context? No – the trial context did not cause changes to intervention Was an appropriate analysis used to estimate the effect of assignment to intervention? Yes – full ITT analysis provided for the metaanalysis outcome of EFS	Low risk Were participants aware of their assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were carers and people delivering the interventions aware of participants’ assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were there deviations from the intended intervention that arose because of the trial context? No – the trial context did not cause changes to intervention Was an appropriate analysis used to estimate the effect of assignment to intervention? Yes – full ITT analysis provided for the metaanalysis outcome of EFS	Low risk Were participants aware of their assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were carers and people delivering the interventions aware of participants’ assigned intervention during the trial? Yes – blinding is not possible in a radiotherapy trial Were there deviations from the intended intervention that arose because of the trial context? No – the trial context did not cause changes to intervention Was an appropriate analysis used to estimate the effect of assignment to intervention? Yes – full ITT analysis provided for the metaanalysis outcome of EFS
3. Risk of bias due to missing outcome data	Low risk Were data available for all, or nearly all, participants randomized? YES, results for event-free survival provided for all patients randomised	Low risk Were data for this outcome available for all, or nearly all, participants randomized? YES, results for event-free survival provided for all patients randomised	Low risk Were data for this outcome available for all, or nearly all, participants randomized? YES, results for event-free survival provided for all patients randomised
4. Risk of bias in measurement of the outcome	Low risk Was method of measuring the outcome inappropriate? NO, used an agreed meta-analysis definition of event-free survival that was suitable across each different trial designs Could measurement of the outcome have differed between intervention groups? NO, used an agreed definition of event-free survival that was suitable for the different intervention groups, and before results were known Outcome assessor aware of intervention received? YES, but unlikely to influence PSA based biochemical failure (the dominant event in the composite outcome). Relatively few clinical and radiological progressions or deaths were reported and unlikely to be affected by outcome assessor	Low risk Was method of measuring the outcome inappropriate? NO, used an agreed meta-analysis definition of event-free survival that was suitable across each different trial designs Could measurement of the outcome have differed between intervention groups? NO, used an agreed definition of event-free survival that was suitable for the different intervention groups, and before results were known Outcome assessor aware of intervention received? YES, but unlikely to influence PSA based biochemical failure (the dominant event in the composite outcome). Relatively few clinical and radiological progressions or deaths were reported and unlikely to be affected by outcome assessor	Low risk Was method of measuring the outcome inappropriate? NO, used an agreed meta-analysis definition of event-free survival that was suitable across each different trial designs Could measurement of the outcome have differed between intervention groups? NO, used an agreed definition of event-free survival that was suitable for the different intervention groups, and before results were known Outcome assessor aware of intervention received? YES, but unlikely to influence PSA based biochemical failure (the dominant event in the composite outcome). Relatively few clinical and radiological progressions or deaths were reported and unlikely to be affected by outcome assessor
5. Risk of bias in selection of the reported result	Low risk Were the data that produced this result analysed in accordance with a pre-specified analysis plan finalized before unblinded outcome data were available for analysis? YES, the data were analysed and supplied in accordance with the meta-analysis protocol that was registered before trial results were known. This is distinct from the trial analysis.	Low risk Were the data that produced this result analysed in accordance with a pre-specified analysis plan finalized before unblinded outcome data were available for analysis? YES, the data were analysed and supplied in accordance with the meta-analysis protocol that was registered before trial results were known. This is distinct from the trial analysis.	Low risk Were the data that produced this result analysed in accordance with a pre-specified analysis plan finalized before unblinded outcome data were available for analysis? YES, the data were analysed and supplied in accordance with the meta-analysis protocol that was registered before trial results were known. This is distinct from the trial analysis.
Overall judgement	Low risk	Low risk	Low risk

PSA= prostate specific antigen; RT= radiotherapy