Lukka NCIC 2005.

Methods	Parallel RCT Setting: tertiary cancer centers, Canada Dates: median 5.7 years (range 4.5–8.3 years) Follow‐up: March 1995–December 1998 Randomization ratio: 1:1 Superiority design: 1‐sided confidence interval
Participants	936 men Inclusion criteria: T1–2 prostate cancer Exclusion criteria: PSA > 40 ng/ml; previous therapy for prostate carcinoma (other than biopsy or TURP); AD; prior or active malignancy other than non‐melanoma skin cancer, colon cancer or thyroid cancer treated a minimum of 5 years before the trial and presumed cured; simulated volume exceeding 1000 mL; previous pelvic RT; presence of inflammatory bowel disease; diagnosis of serious non‐malignant disease that would preclude RT or surgical biopsy; geographically inaccessible for follow‐up; a psychiatric or addictive disorder that would preclude obtaining informed consent or adherence to protocol; inability to commence RT within 26 weeks of the date of last prostatic biopsy; and failure to provide informed consent to participate in the clinical trial. Diagnostic criteria: adenocarcinoma prostate
Interventions	Number of study centers: 16 Run‐in period: not stated Extension period: no Experimental arm: 466/466 participants Conventional arm: 470/470 participants Complex interventions: Experimental arm: 52.5 Gy in 20 fractions over 4 weeks Conventional arm: 66 Gy in 33 fractions over 6.5 weeks
Outcomes	Primary outcomes 5‐year BR‐FS Secondary outcomes 2‐year biopsy OS Acute (< 5 months) and late toxicity (> 5 months) (GI, GU, skin, general) Complete outcome measures reported: yes
Funding sources	National Cancer Centre Ontario and the National Cancer Institute of Canada Clinical Trials Group
Declarations of interest	Quote: "The authors indicated no potential conflicts of interest", page 6137, paragraph 8.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "Patients were assigned to one of two treatment regimens according to a central computer‐generated randomization schedule within", page 6133. Treatment regimens, paragraph 1. Comment: we deemed this at low risk of bias, because a computer‐generated randomization schedule was used.
Allocation concealment (selection bias)	Low risk	Quote from publication: "a central computer‐generated randomisation schedule … ", page 6133. Treatment regimens, paragraph 1. Comment: we deemed this at low risk of bias, because allocation was managed centrally; therefore, we thought it was concealed.
Blinding of participants and personnel (performance bias) Subjective outcomes	Unclear risk	Not mentioned, we deemed this domain at unclear risk of bias PC‐SS: unclear risk of bias Late EORTC/RTOG GI RT toxicity: not reported Late EORTC/RTOG GU RT toxicity: not reported M‐FS: not reported BR‐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 participants and personnel (performance bias) Objective outcomes	Low risk	Not mentioned, 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	Low risk	Quote from publication: "Blinded assessment was used to verify the occurrence of biochemical or clinical failure and to determine the earliest date of failure", page 6133. Outcomes, paragraph 1. Comment: we deemed these outcomes at low risk of bias because of this blinding M‐FS: low risk of bias BR‐FS: low risk of bias PC‐SS: low risk of bias Quote from publication: "The investigating clinician or clinical trials nurse assessed radiation toxicity using the standardised National Cancer Institute of Canada toxicity scale", page 6134. Outcomes, paragraph 3. Comment: there is no mention of blinding of outcome assessors, it was probably not done, though there was a prespecified follow‐up schedule, these outcomes were deemed at unclear risk of bias. Late GI RT toxicity: low risk of bias, not reported Late GU RT toxicity: low risk of bias, not reported Acute GI RT toxicity: low risk of bias, not reported Acute GU RT toxicity: low risk of bias, not reported Health‐related quality of life: low risk of bias, not reported
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Blinding not mentioned, deemed at low risk of bias OS: low risk of bias Second malignancy: not reported
Incomplete outcome data (attrition bias)	Low risk	Quote from publication: "During the study, seven patients did not receive radiation (five patients in the long arm and two patients in the short arm …)", page 6134. Study population, paragraph 2. Comment: there is no mention of exclusions or attrition, but in the tables, all participants randomized were included. All men randomized were included in the analysis so we deemed this at low risk of bias. Number of participants reported on by outcome PC‐SS: 936/936 Late EORTC/RTOG GI RT toxicity: not reported in usable form Late EORTC/RTOG GU RT toxicity: not reported in usable form OS: 936/936 DM‐FS: not reported in usable form BR‐FS: not reported in usable form Acute EORTC/RTOG GI RT toxicity: not reported in usable form Acute EORTC/RTOG GU RT toxicity: not reported in usable form Second malignancy: not reported Quality of life: not assessed
Selective reporting (reporting bias)	Low risk	Outcomes specified: BCF, radiation toxicity (GI and GU) Outcomes reported: BCF, OS, prostate cancer deaths, prostate biopsy at 2 years, radiation toxicity We did not have access to the study protocol. We deemed this domain at low risk of bias.
Other bias	Low risk	Quote from publication: "Although the trial was originally designed with biopsy positivity at 2 years after randomization as the primary outcome, the emerging literature suggested that the combination of BCF was the optimal measure of efficacy … Therefore, before the study completion and data un‐blinding, an amendment was issued and approved by the study Steering Committee (September 14, 2001) to change the primary outcome to BCF. The protocol modification was then distributed to all participating clinical centres", page 6133. Outcomes, paragraph 1. Comment: although there was a change made in the primary outcome measure, this was done prior to unblinding, so we did not consider it a source of bias.