Summary of findings 1. Different bone‐modifying agents compared with each other and no treatment/placebo for men with prostate cancer and bone metastases.
| Different bone‐modifying agents compared with each other and no treatment/placebo for men with prostate cancer and bone metastases | |||
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Patient or population: prostate cancer patients with bone metastases Setting: castration‐resistant and castration‐sensitive patients Intervention: zoledronic acid, denosumab Comparison: no treatment/placebo | |||
| Outcomes | Absolute effects and relative effects with 95% CIs. Main comparator: no treatment/placebo | ||
| Assumed risk with no treatment/placebo* | Corresponding risk with zoledronic acid | Corresponding risk with denosumab | |
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Proportion of participants with pain response (network based on 4 studies including 1013 participants; follow‐up 5‐12 months) |
Response 265 per 1000 (26.5%) |
Response 386 per 1000 (246 to 614) |
‐ |
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RR 1.46 (0.93 to 2.32) |
‐ | ||
| ⊕⊕⊕⊝ Moderate1 | ‐ | ||
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Adverse event: renal impairment (network based on 6 studies including 1769 participants; follow‐up 5‐36 months) |
124 per 1000 (12.4%) |
202 per 1000 (134 to 304) |
‐ |
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RR 1.63 (1.08 to 2.45) |
‐ | ||
| ⊕⊕⊕⊝ Moderate2 | ‐ | ||
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Adverse event: osteonecrosis of the jaw (network based on 4 studies including 3006 participants; follow‐up 5‐24 months) |
12 per 1000 (1.2%) |
23 per 1000 (9 to 59) |
42 per 1000 (13 to 137) |
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RR 1.88 (0.73 to 4.87) |
RR 3.45 (1.06 to 11.24) |
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| ⊕⊕⊕⊝ Moderate1 | ⊕⊕⊕⊕ High | ||
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Skeletal‐related events total (network based on 12 studies including 5240 participants; follow‐up 5‐60 months) |
468 per 1000 (46.8%) |
393 per 1000 (337 to 454) |
337 per 1000 (253 to 449) |
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RR 0.84 (0.72 to 0.97) |
RR 0.72 (0.54 to 0.96) |
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| ⊕⊕⊝⊝ Low2,3 | ⊕⊕⊝⊝ Low2,3 | ||
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Mortality (network based on 13 studies including 5494 participants; follow‐up 12‐60 months) |
484 per 1000 (48.4%) |
436 per 1000 (387 to 489) |
450 per 1000 (373 to 538) |
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RR 0.90 (0.80 to 1.01) |
RR 0.93 (0.77 to 1.11) |
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| ⊕⊕⊕⊝ Moderate1 | ⊕⊕⊕⊝ Moderate1 | ||
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Quality of life (narrative based on 1 study including 1904 participants) Assessed via Functional Assessment of Cancer Therapy‐General questionnaire, follow‐up 18 months) |
More zoledronic acid‐treated patients than denosumab‐treated patients experienced a greater than or equal to five‐point decrease in Functional Assessment of Cancer Therapy‐General total scores (average relative difference = 6.8%, range ‐9.4 to 14.6%) or worsening of cancer‐related quality of life | ||
| ⊕⊕⊕⊝ Moderate1 | |||
| *The basis for the assumed risk/response (e.g. the median control group risk/response across studies) was calculated from the included trials in the network of each outcome. The corresponding likelihood (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio | |||
| GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: 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 certainty: We are very uncertain about the estimate. | |||
1Downgraded 1 level for imprecision since 95% confidence interval wide and cross unity. 2Downgraded 1 level for inconsistency (heterogeneity) since prediction intervals compared to confidence intervals would change clinical decision (but not the ranking of treatment options). 3Downgraded 1 level for serious risk of bias, mostly regarding blinding. Downgraded if outcome of interest was considered subjective in these cases.