SAKK 08/88.

Methods	Design: randomized controlled trial Setting: multicentric Recruiting period: 1988 to 1992 Sample size: 197 patients Follow‐up (months): not reported
Participants	Population description: patients with T0‐4, N0‐2, M0‐1 newly diagnosed asymptomatic prostate cancer without previous treatment not suitable or unwilling for local curative therapy Inclusion criteria: histologically or cytologically proven, newly diagnosed asymptomatic (with the exception of voiding disturbances) carcinoma of the prostate T0‐4, N0‐2, M0‐1 not suitable for local treatment with curative intent (radical prostatectomy, radiation therapy) patients with bone metastases, regional lymph node or soft tissue metastases smaller than 5 cm (N0‐2), determined either by CT or ultrasonography, preferably with cytologic confirmation life expectancy of at least 6 months WHO performance status score 0‐2 Exclusion criteria: other malignancies diagnosed during the previous 10 years, apart from adequately treated basal cell carcinoma of the skin; prostate cancer known > 2 months before entering the study patients with palpable or juxtaregional lymph node metastasis (paraaortic, supraclavicular, inguinal, N3‐4) pain caused by the prostate cancer or its metastases any previous treatment for prostate cancer (radical prostatectomy, radiation therapy, endocrine treatment and so on); TURP for voiding disturbances was allowed at any time and was not an exclusion criterion patients with ureteric obstruction caused by local infiltration of prostatic cancer or other evidence of locally advanced disease that could cause fatal complications if untreated (e.g., rectal stenosis, thrombosis of pelvic veins) Tumour stage: T0‐4, N0‐2, M0‐1 Previous treatment: no previous treatment Number randomised: 197 patients Withdrawals and exclusions: 9 patients (4 in immediate arm; 5 in deferred arm) Subgroup measured: M0 vs. M1, WHO performance 0‐1 vs. 2, tumour stage T0‐2 vs. T3‐4, lymph node status N0 vs N1‐2 Subgroup reported: not reported Age: median age: 76 years (range: 56 to 86) immediate treatment: median 76 years (range: 57 to 86) deferred treatment: median 77 years (range: 56 to 85) Baseline imbalances: no significant differences between the groups
Interventions	Early ADT (intervention group): route of administration: surgical intervention frequency, dose: subcapsular orchiectomy number of patients randomised: 100 (analysed 96) Deferred ADT (control group): route of administration: surgical intervention frequency, dose: subcapsular orchiectomy definition of deferred ADT: same treatment at the onset of symptoms caused by metastases or when ureteric obstruction or new asymptomatic metastases were likely to cause severe complications (pathologic fractures, spinal palsy etc.). Biochemical progression such as increasing prostate‐specific antigen or phosphatase, new hot spots, or soft tissue metastases during follow‐up did not justify deferred orchiectomy as long as the patient remained asymptomatic and did not have a decrease in performance status number of patients randomised: 97 (analysed 92)
Outcomes	Primary outcome(s): overall survival (defined as the interval from the date of random assignment to the date of death as a result of any cause) Secondary outcome(s): overall post‐treatment symptom‐free survival (defined as the interval from random assignment to the first symptoms of hormone‐refractory prostate cancer after immediate or deferred orchiectomy) cancer specific survival (defined as the time from random assignment to death as a result of prostate cancer) pain‐free interval (defined as the time from random assignment to first occurrence of pain after immediate or deferred treatment) adverse events (incidence of complications or symptomatic progression)
Funding sources	Not reported
Declaration of interest	The author indicated no potential conflicts of interest
Notes	Patient accrual was stopped prematurely because of similar competing trial: the trial was closed in February 1992 because the European Organization for Research and Treatment of Cancer trial 30891 with a similar objective, but including only M0 patients, was opened at that time. To avoid selection bias with predominantly M1 patients in this SAKK 08/88 trial, it was closed prematurely, but the observation time was prolonged until more than 90% of patients had died. This allowed the acquisition of the necessary number of events for an adequate statistical power of 88%. The power analysis was based on a sample of 188 patients, the achieved total of 172 events, an accrual duration of 4 years, and a hypothesized difference of 15% in 5‐year overall survival.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information from publication: Information was not reported. Comment: We assume that randomisation was performed adequately at the Swiss Group for Clinical Cancer Research (SAKK) coordinating centre. However, information was not reported and there is therefore unclear risk of bias.
Allocation concealment (selection bias)	Low risk	Information from publication: "Central allocation"..."Registration was performed at the Swiss Group for Clinical Cancer Research (SAKK) coordinating centre (Bern, Switzerland) by telephone". Comment: Adequate allocation concealment.
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 outcome assessment for 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	For early ADT, 100 patients were randomised and 96 (96%) were in analysis. For deferred ADT, 97 patients were randomised and 92 (94.8%) were in analysis. The proportion of patients that were not in analysis is less than 10% and risk of attrition bias is therefore likely to be low.
Incomplete outcome data (attrition bias) Adverse events (Serious and other adverse events)	Low risk	For early ADT, 100 patients were randomised and 96 (96 %) were in analysis. For deferred ADT, 97 patients were randomised and 92 (94.8%) were in analysis. The proportion of patients that were not in analysis is less than 10% and risk of attrition bias is therefore likely to be low.
Incomplete outcome data (attrition bias) Quality of life	Unclear risk	Not applicable (outcome not measured/reported).
Selective reporting (reporting bias)	Unclear risk	Adverse events were measured but we assume that they are only partially reported leading to unclear risk of bias.
Other bias	Unclear risk	We identified no other sources of bias.