Yeoh 2011.

Methods	Parallel RCT Setting: tertiary cancer center, Australia Dates: July 1996–August 2003 Follow‐up: median 90 months (range 3–138 months) Randomization ratio: 1:1 Superiority design CCT
Participants	217 men Inclusion criteria: T1–2N0M0 prostate cancer Exclusion criteria: PSA > 80 ng/mL, AD Diagnostic criteria: not stated
Interventions	Number of study centers: 1 Run‐in period: not stated Extension period: no Experimental arm: 108/108 participants Conventional arm: 109/109 participants Complex interventions: Experimental arm (n = 108): 55 Gy in 20 fractions over 4 weeks Conventional arm (n = 109): 64 Gy in 32 fractions over 6.5 weeks (see Table 8)
Outcomes	Primary outcomes 2‐year late GI/GU toxicity Secondary outcomes FFBR Clinical recurrence OS Complete outcome measures reported: yes (late GI/GU toxicity, FFBR, OS)
Funding sources	Not stated
Declarations of interest	Not stated
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "Patient randomization was done using blocked computer generated numbers", page 1272, 2011. Comment: we deemed this at low risk of bias
Allocation concealment (selection bias)	Low risk	Quote from publication: "randomization was … administered by data managers", page 1272, 2011. Comment: we deemed this concealed, so at low risk of bias
Blinding of participants and personnel (performance bias) Subjective outcomes	Unclear risk	Blinding not mentioned, probably not done, we deemed this domain at unclear risk of bias. PC‐SS: unclear risk of bias Late EORTC/RTOG GI RT toxicity: not reported in usable form Late EORTC/RTOG GU RT toxicity: not reported in usable form M‐FS: not reported BR‐FS: unclear risk of bias Acute EORTC/RTOG GI RT toxicity: not reported Acute EORTC/RTOG GU RT toxicity: not reported Health‐related quality of life: not reported
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Blinding not mentioned, probably not done, we deemed this domain at low risk of bias. OS: low risk of bias Second malignancy: not reported
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	There was no mention of blinding of outcome assessors for subjective outcomes (toxicity), even though there was a validated scoring tool used, we considered this domain at unclear risk of bias. PC‐SS: unclear risk of bias Late EORTC/RTOG GI RT toxicity: not reported in usable form Late EORTC/RTOG GU RT toxicity: not reported in usable form M‐FS: not reported Acute EORTC/RTOG GI RT toxicity: not reported Acute EORTC/RTOG GU RT toxicity: not reported Health‐related quality of life: not reported
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Although there was no mention of blinding, and it was probably not done, the prespecified timing of PSA measurement would make the assessment of biochemical relapse not subject to bias, so this we deemed at low risk of bias. BR‐FS: not a compound endpoint, defined by PSA rise, low risk of bias OS: low risk of bias Second malignancy: not reported
Incomplete outcome data (attrition bias)	High risk	Number of participants reported on by outcome PC‐SS: not reported Late EORTC/RTOG GI RT toxicity: not reported using this scale Late EORTC/RTOG GU RT toxicity: not reported using this scale Quote from publication: "Of the 217 patients, 101 had been lost to follow‐up and 65 had < 5 years of follow‐up, mainly because advancing age and ill health associated with medical co‐morbidities and domicile distant from the centres equipped with the resources for proper evaluation of their disease prevented travel", page 1273, 2011. Comment: we deemed this domain at high risk of bias. OS: reported in 116/217 randomized participants DM‐FS: not reported Quote from publication: "2 year PSA data available for 208 (96%) of patients … after 2 years, 76 patients had elected to attend elsewhere and 35 patients had died (31 of these died of causes unrelated to prostate cancer … 5‐year PSA … were available in 96 of the 217 patients)", page 1076. Results, paragraph 1. BR‐FS: reported in 96/217 randomized participants Acute EORTC/RTOG GI RT toxicity: not reported Acute EORTC/RTOG GU RT toxicity: not reported Second malignancy: not reported Quality of life: not reported
Selective reporting (reporting bias)	Unclear risk	Outcomes specified: acute and late GI and GU toxicity Outcomes reported: acute and late GI and GU toxicity, biochemical failure, sites of clinical relapse and OS. We did not have access to the study protocol. We deemed this domain at unclear risk of bias.
Other bias	Low risk	The study stopped early. Quote from publication: "because of full implementation of 3D CRT at the institution", page 1073, paragraph 3. Comment: we did not consider this a source of other bias.

3DCRT: three‐dimensional conformal radiation therapy; AD: androgen deprivation; AJCC: American Joint Committee on Cancer; BCDF: biochemical or clinical disease failure, or both; BCF: biochemical or clinical failure; BR‐FS: biochemical relapse‐free survival; CCT: controlled clinical trial; CT: computer tomography; D‐FS: disease‐free survival; DM: distant metastases; DM‐FS: distant metastases‐free survival; EORTC: European Organisation for Research and Treatment of Cancer; EPIC: Expanded Prostate Cancer Index Composite; FACT‐P: Functional Assessment of Cancer Therapy – Prostate (Esper 1997); FFBR: freedom from biochemical relapse; GI: gastrointestinal; GU: genitourinary; IGRT: image‐guided radiation therapy; IMRT: intensity‐modulated radiation therapy; M‐FS: metastasis‐free survival; n: number of participants; OS: overall survival; PC‐SS: PC‐SS; PS: performance scale; PSA: prostate‐specific antigen; PTV: planning target volume; R‐FS: relapse‐free survival; RCT: randomized controlled trial; RT: radiation therapy; RTOG: Radiation Therapy Oncology Group; TURP: transurethral resection of the prostate; UCLA‐PCI: University of California, Los Angeles Prostate Cancer Index (Litwin 1998); WHO: World Health Organization.