Sciarra 2004a.

Methods	Start date, end date of recruitment: between December 1998 and January 2001 Follow‐up period: After radical retropubic prostatectomy, when serum PSA levels exceeded 0.2 ng/mL, PSA determinations were repeated every 2 weeks. Participants entered the study once their PSA level progressed, defined as 3 or more consecutive elevated levels (greater than 0.4 ng/mL) Serum CgA levels were analysed at baseline (PSA progression) and at 1, 3, 6, 12, 18 and 24 months after random assignment. Total PSA levels were measured every 4 weeks for the first 12 months of treatment and every 8 weeks thereafter Design: randomised controlled trial
Participants	Population/Inclusion criteria: Men with pT3pN0M0 prostate cancer and biochemical progression (defined as PSA level greater than 0.4 ng/mL) within 12 months of radical retropubic prostatectomy were enrolled. Other inclusion criteria were histologically proven prostate cancer; no preoperative hormonal therapy or radiotherapy; radical retropubic prostatectomy with regional lymphadenectomy performed at our institution; and negative surgical margins Setting: single centre Geographical location: Italy Exclusion criteria: not reported Total number randomly assigned: 186 men with clinically localised prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at our institution; 59 fulfilled inclusion criteria and agreed to random assignment. Only the 48 men who concluded and successfully responded to the first 24 months of treatment were analysed Baseline imbalances: balanced Number of participants with non‐metastatic disease: 48 Number of participants with metastatic disease: 0 Age (mean ± SD): intervention: 64.2 ± 3.7 years (range 54 to 70 years); control: 64.8 ± 3.5 years (range 56 to 70 years) PSA (mean ± SD): PSA at baseline (progression after prostatectomy) in non‐steroidal antiandrogen group: 1.12 ± 0.32 ng/mL (median 1.0 ng/mL; range 0.60 to 1.80 ng/mL); PSA at baseline (progression after prostatectomy) in castration group: 1.05 ± 0.30 ng/mL (median 1.0 ng/mL; range 0.60 to 1.60 ng/mL) Subgroup measured: no
Interventions	Intervention Description/Timing: bicalutamide 150 mg daily Number randomly assigned to this group: unclear (analysed and reported: 24) Control Description/Timing: triptorelin 3.75 mg monthly Number randomly assigned to this group: unclear (analysed and reported: 24)
Outcomes	Overall survival Outcome not measured/reported Cancer‐specific mortality Outcome not measured/reported Treatment discontinuation due to adverse events Outcome not measured/reported Clinical progression Comparison: non‐steroidal antiandrogen versus castration Subgroup: no Time points measured: at 24 months Time points reported: at 24 months Outcome definition in report: Treatment was considered to have failed when the PSA level increased to greater than 0.4 ng/mL or at clinical progression. Biopsy of the urethrovesical anastomosis, abdominal‐pelvic magnetic resonance imaging and a total body bone scan were performed 12 and 24 months after random assignment or at PSA progression Number of participants randomly assigned: intervention: unclear; control: unclear Number of participants in evaluation for ITT: intervention: 24; control: 24 Biochemical progression Comparison: non‐steroidal antiandrogen versus castration Subgroup: no Time points measured: at 24 months Time points reported: at 24 months Outcome definition in report: Treatment was considered to have failed when the PSA level increased to greater than 0.4 ng/mL or at clinical progression. Biopsy of the urethrovesical anastomosis, abdominal‐pelvic magnetic resonance imaging and a total body bone scan were performed 12 and 24 months after random assignment or at PSA progression Number of participants randomly assigned: intervention: unclear; control: unclear Number of participants in evaluation for ITT: intervention: 24; control: 24 Treatment failure (outcome measured but not reported) Comparison: non‐steroidal antiandrogen versus castration Subgroup: no Time points measured: at 24 months Time points reported: at 24 months Outcome definition in report: Treatment was considered to have failed when the PSA level increased to greater than 0.4 ng/mL or at clinical progression. Biopsy of the urethrovesical anastomosis, abdominal‐pelvic magnetic resonance imaging and a total body bone scan were performed 12 and 24 months after random assignment or at PSA progression Number of participants randomly assigned: intervention: unclear; control: unclear Number of participants in evaluation for ITT: intervention: 24; control: 24 Adverse events Outcome not measured/reported Other outcomes reported Serum CgA levels
Notes	During the first 24 months of follow‐up, no participant showed evidence of clinical progression, and the PSA serum levels remained at 0.4 ng/mL or less Study funding source: unclear Possible conflict of interest: unclear
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) overall survival, cancer‐specific mortality, biochemical progression	Unclear risk	No blinding for biochemical progression. Blinding was not possible because of different interventions provided. It might be conceivable that biochemical progression is influenced by lack of blinding. We finally judge that risk of bias regarding this outcome is unclear
Blinding of participants and personnel (performance bias) treatment discontinuation due to adverse events, clinical progression, treatment failure, adverse events	High risk	No blinding for clinical progression and treatment failure. Blinding was not possible because of different interventions provided. We judge that outcomes such as clinical progression and treatment failure are likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) overall survival, cancer‐specific mortality, biochemical progression	Low risk	No blinding for biochemical progression. Blinding was not possible because of different interventions provided, and study authors reported insufficient information only. However, we judge that it is not likely that outcome assessment for biochemical progression is influenced by lack of blinding
Blinding of outcome assessment (detection bias) treatment discontinuation due to adverse events, clinical progression, treatment failure, adverse events	High risk	No blinding for clinical progression and treatment failure. Blinding was not possible because of different interventions provided, and study authors reported insufficient information only. We judge that it is likely that outcome assessment for clinical progression and treatment failure is influenced by lack of blinding
Incomplete outcome data (attrition bias) overall survival, cancer‐specific mortality	Unclear risk	Not measured/reported
Incomplete outcome data (attrition bias) treatment discontinuation due to adverse events, adverse events	Unclear risk	Not measured/reported
Incomplete outcome data (attrition bias) clinical progression, biochemical progression	High risk	'As‐treated' analysis on clinical/biochemical progression done with substantial departure of the intervention received from that assigned at randomisation (59 men fulfilled the inclusion criteria and agreed to random assignment; only the 48 participants who concluded and successfully responded to the first 24 months of treatment were analysed)
Incomplete outcome data (attrition bias) treatment failure	High risk	Outcome measured but not reported
Selective reporting (reporting bias)	High risk	Study report fails to include results for a key outcome that would be expected to have been reported for such a study (no data on adverse events, treatment discontinuation due to adverse events or treatment failure reported). No protocol available
Other bias	Unclear risk	Unclear risk for conflict of interest