MRC.

Methods	Design: randomised controlled trial Setting: multicentric Recruiting period: 1985 to 1993 Sample size: 934 patients Follow‐up (months): each year, shortly after the anniversary of entry (duration of follow‐up is not reported)
Participants	Population description: locally advanced or asymptomatic metastatic prostate cancer Inclusion criteria: histological evidence of adenocarcinoma of the prostate hormone therapy was essential local disease considered too advanced for curative treatment (i.e. T2‐T4) metastatic disease not causing symptoms ECOG performance status of 0‐2 and no other immediately life‐threatening disease, with an expected survival ≥ 12 months Exclusion criteria: previous hormonal treatment Tumour stage: T2‐T4, M0‐M1, Mx (patients with no evidence of metastatic disease, but with no confirmation by a bone scan ) Previous treatment: patients could undergo a therapeutic or diagnostic TURP or radiotherapy Number randomised: 934 patients Withdrawals and exclusions: analysis by intention‐to‐treat Subgroup measured: metastatic disease (M1), advanced but non‐metastatic disease (M0) and patients with no evidence of metastatic disease, but with no confirmation by a bone scan (Mx; n = 174). Because of the number of patients with uncertain disease classification, we included data of all patients irrespective of subgroups. Subgroup reported: metastatic disease (M1), advanced but non‐metastatic disease (M0) and patients with no evidence of metastatic disease, but with no confirmation by a bone scan (Mx) Age: not reported Baseline imbalances: a ‘minimization’ algorithm used to limit chance differences between groups in age, T category and metastatic status
Interventions	Early ADT (intervention group): route of administration: surgical intervention or s.c. injections frequency, dose: orchiectomy (total or subcapsular) or luteinizing hormone‐releasing hormone analogue within 6 weeks of entry or if for any reason either of these options became inappropriate, an alternative form of effective hormone therapy was allowed (cryptoterone acetate, oestrogens, flutamide) number of patients randomised: 469 patients Deferred ADT (control group): route of administration: surgical intervention or s.c. injections frequency, dose: orchiectomy (total or subcapsular) or luteinizing hormone‐releasing hormone analogue within 6 weeks of entry or if for any reason either of these options became inappropriate, an alternative form of effective hormone therapy was allowed (cryptoterone acetate, oestrogens, flutamide) definition of deferred ADT: same treatment until an indication occurred (pain from or complications of bone metastases, local progression, increasing tumour marker level, general systemic effects, patient preference). Indications for treatment in deferred patients were at the discretion of the participant. Patients allocated to deferred treatment were followed up according to the practice of the participant until an indication to commence hormone treatment occurred. number of patients randomised: 465 patients
Outcomes	Primary outcome(s): overall survival (defined as time to death from any cause) deaths from prostate cancer deaths from other causes than prostate cancer major complications (pathological fracture, cord compression, ureteric obstruction, extra skeletal metastases) due to disease progression
Funding sources	not reported
Declaration of interest	not reported
Notes	Participants otherwise managed their patients according to their clinical practice. In the hope that a substantial number of busy working urologists could be recruited, entry and follow‐up were simplified as much as possible, and only data considered relevant to the main issue were collected. As an aid to recruitment, it was intended to simplify registration and to allow investigators to adopt as much of their routine practice as possible. It transpired that many British urologists did not have ready access to bone‐scan facilities. Thus, the simple stratification into M0 and M1 disease envisaged in the protocol had to be modified. An additional category, Mx, was introduced and the categories defined as: M0, patients with no evidence of metastatic disease, confirmed by a negative bone scan; Mx, patients with no evidence of metastatic disease, but with no confirmation by a bone scan; M1, patients with definite scintigraphic, radiological or other evidence of metastatic disease.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information from publication: Information not reported. Comment: It was only reported that during the registration/randomisation telephone call essential baseline details were recorded on computer and a ‘minimization’ algorithm used to limit chance differences between groups in age, T category and metastatic status.
Allocation concealment (selection bias)	Unclear risk	Information from publication: Information not reported. Comment: It was only reported that patients were registered and randomised by a single telephone call to the trial office.
Blinding of participants and personnel (performance bias) Time to death of any cause	Unclear risk	Information from publication: There was no blinding. Comment: It might be conceivable that even time to death of any cause is influenced by lack of blinding. We finally judge that there is an unclear risk of bias.
Blinding of participants and personnel (performance bias) All other outcomes	High risk	Information from publication: There was no blinding. Comment: We judge that time to disease progression, time to death from prostate cancer and adverse events are likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Time to death from any cause	Low risk	Information from publication: There was no blinding of outcome assessment (or it was not reported). Comment: Blinding of outcome assessment could have been expected. However, we judge that it is not likely that time to death of any cause is influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All other outcomes	High risk	Information from publication: There was no blinding of outcome assessment (or it was not reported). Comment: Blinding of outcome assessment could have been expected. We judge that outcome assessment of time to disease progression, time to death from prostate cancer and adverse events is likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) Oncological outcomes (Time‐to‐death of any cause, Time‐to‐disease progression, Time‐to‐death from prostate cancer)	Low risk	There is no evidence for missing outcome data; all patients randomised were included in the analyses. However, no data for disease progression were reported for all included participants (M1+M0); only participants with M0 disease were reported.
Incomplete outcome data (attrition bias) Adverse events (Serious and other adverse events)	Unclear risk	Not applicable (outcome was not measured/reported).
Incomplete outcome data (attrition bias) Quality of life	Unclear risk	Not applicable (outcome was not measured/reported).
Selective reporting (reporting bias)	Unclear risk	The protocol is not available but we think that all outcomes were reported. The methodology of the study was not planned for evaluating adverse events. However, it could have been expected for a randomised controlled trial leading to unclear risk of bias.
Other bias	Unclear risk	We identified no other sources of bias.