Summary of findings for the main comparison. Non‐steroidal antiandrogen monotherapy versus LHRH agonists or surgical castration monotherapy for advanced prostate cancer.
| Non‐steroidal antiandrogen monotherapy versus LHRH agonists or surgical castration monotherapy for advanced prostate cancer | ||||||
|
Patient or population: men with advanced prostate cancer
Settings: multi‐centre (9 studies) and single‐centre studies (2 studies) on outpatients
Intervention: non‐steroidal antiandrogen monotherapy Comparison: LHRH agonists or surgical castration monotherapy | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Hazard ratio/ Relative effect (95% CI) | No. of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Castration | Non‐steroidal antiandrogen | |||||
| Overall survival Follow‐up: median 1 to 6.3 years | 296 per 1000 | 353 per 1000 (308 to 405) | HR 1.24 (1.05 to 1.48) | 2712 (6 studies) | ⊕⊕⊕⊝ moderate1,6 | Overall survival was evaluated using the random‐effects model because of heterogeneity (I2 = 51%). Sensitivity analyses showed comparable results. Numbers of absolute risks relate to deaths |
| Clinical progression Follow‐up: median 70 weeks | 420 per 1000 | 529 per 1000 (453 to 608) | RR 1.26 (1.08 to 1.45) | 2373 (6 studies) | ⊕⊕⊕⊝ moderate2,6 | Clinical progression after median 70 weeks was evaluated using the random‐effects model because of heterogeneity (I2 = 64%). Sensitivity analyses showed comparable results. After imputation of event numbers: RR 1.43, 95% CI 1.19 to 1.73, I2 = 0%; fixed‐effect model |
| Treatment failure Follow‐up: median 70 weeks | 527 per 1000 | 669 per 1000 (553 to 801) | RR 1.27 (1.05 to 1.52) | 1845 (5 studies) | ⊕⊕⊕⊝ moderate3,6 | Treatment failure after median 70 weeks was evaluated using the random‐effects model because of heterogeneity (I2 = 81%). Sensitivity analyses showed comparable results. After imputation of event numbers: RR 1.21, 95% CI 1.09 to 1.35, I2 = 0%; fixed‐effect model |
| Breast pain Follow‐up: median 1 to 6.3 years | 17 per 1000 | 397 per 1000 (256 to 617) | RR 22.97 (14.79 to 35.67) | 2670 (8 studies) | ⊕⊕⊕⊝ moderate4 | Breast pain was evaluated using the fixed‐effect model (I2 = 0%) |
| Gynaecomastia Follow‐up: median 1 to 6.3 years | 44 per 1000 | 374 per 1000 (142 to 989) | RR 8.43 (3.19 to 22.28) | 2774 (9 studies) | ⊕⊕⊕⊝ moderate5,6 | Gynaecomastia was evaluated using the random‐effects model because of heterogeneity (I2 = 92%). Sensitivity analyses showed comparable results |
| Hot flashes Follow‐up: median 1 to 6.3 years | 451 per 1000 | 104 per 1000 (86 to 122) | RR 0.23 (0.19 to 0.27) | 2774 (9 studies) | ⊕⊕⊕⊝ moderate5 | Hot flashes were evaluated using the fixed‐effect model (I2 = 0%) |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). LHRH: Luteinising hormone‐releasing hormone; CI: Confidence interval; HR: Hazard ratio; RR: Risk ratio. | ||||||
| GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1Downgraded for study limitations (‐1): high risk of bias: 'allocation concealment' (Tyrrell 2006); unclear risk of bias: 'random sequence generation' (Study 0301; Study 0302; Study 0303; Study 306; Study 307); 'allocation concealment' (Study 0301;Study 0302; Study 0303; Study 306; Study 307); 'blinding of participants and personnel' (all included studies); 'other bias' (all included studies). 2Downgraded for study limitations (‐1): high risk of bias: 'blinding of participants and personnel' (all included studies); 'blinding of outcome assessment' (all included studies); 'incomplete outcome data' (Sciarra 2004a; Study 0301;Study 0302;Study 0303); 'selective reporting' (Sciarra 2004a); unclear risk of bias: 'random sequence generation' (all included studies); 'allocation concealment' (all included studies); 'other bias' (all included studies). 3Downgraded for study limitations (‐1): high risk of bias: 'blinding of participants and personnel' (all included studies); 'blinding of outcome assessment' (all included studies); 'incomplete outcome data' (Study 0301;Study 0302;Study 0303); unclear risk of bias: 'random sequence generation' (all included studies); 'allocation concealment' (all included studies); 'other bias' (all included studies). 4Downgraded for study limitations (‐1): high risk of bias: 'allocation concealment' (Tyrrell 2006); 'blinding of participants and personnel' (Sieber 2004;Study 0301;Study 0302;Study 0303; Study 306; Study 307; Tyrrell 2006); 'blinding of outcome assessment' (Sieber 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307; Tyrrell 2006); 'incomplete outcome data' (Study 0301; Study 0302; Study 0303); unclear risk of bias: 'random sequence generation' (Sieber 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307); 'allocation concealment' (Sieber 2004; Smith 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307); 'blinding of participants and personnel' (Smith 2004); 'blinding of outcome assessment' (Smith 2004); 'other bias' (all included studies). 5Downgraded for study limitations (‐1): high risk of bias: 'allocation concealment' (Tyrrell 2006); 'blinding of participants and personnel' (Boccon‐Gibod 1997; Sieber 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307; Tyrrell 2006); 'blinding of outcome assessment' (Boccon‐Gibod 1997; Sieber 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307; Tyrrell 2006); 'incomplete outcome data' (Study 0301; Study 0302; Study 0303); unclear risk of bias: 'random sequence generation' (Boccon‐Gibod 1997; Sieber 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307); 'allocation concealment' (Sieber 2004; Smith 2004; Study 0301; Study 0302; Study 0303; Study 306; Study 307); 'blinding of participants and personnel' (Smith 2004); 'blinding of outcome assessment' (Smith 2004); 'other bias' (all included studies). 6Heterogeneity was present but might be explained by subgroup or sensitivity analyses (see Effects of interventions; Quality of the evidence); therefore we did not downgrade for inconsistency.