Summary of findings 1. Gemcitabine compared to saline.
| Patient or population: participants with non‐muscle invasive bladder cancer (607 men, 127 women) Country: Germany, Turkey, and the US Setting: multicenter, likely inpatients Intervention: gemcitabine Comparison: saline | |||||
| Outcomes | № of participants (studies) | Certainty of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects* (95% CI) | |
| Risk with saline | Risk difference with gemcitabine | ||||
|
Time to recurrence (absolute effect size estimates based on recurrence rate at 4 years) Follow‐up: range 2–4 years MCID: 5% absolute difference |
734 (2 RCTs) | ⊕⊕⊝⊝ Lowa,b,c | HR 0.77 (0.54 to 1.09) | Moderate | |
| 470 per 1000e | 83 fewer per 1000 (180 fewer to 29 more) | ||||
|
Time to progression (absolute effect size estimates based on progression rate at 4 years) Follow‐up: range 2–4 years MCID: 5% absolute difference |
654 (2 RCTs) | ⊕⊕⊝⊝ Lowa,b,c | HR 0.96 (0.19 to 4.71) | Low | |
| 48 per 1000e | 2 fewer per 1000 (39 fewer to 159 more) | ||||
|
Grade III–V adverse events
assessed with: 1 study: measured as serious adverse events; 1 study: CTCAE version 3.0 and version 4.0 Follow‐up: range 1–3 months MCID: 5% absolute difference |
668 (2 RCTs) | ⊕⊕⊝⊝ Lowa,c | RR 1.26 (0.58 to 2.75) | Study population | |
| 47 per 1000 | 12 more per 1000 (20 fewer to 83 more) | ||||
|
Time to death from bladder cancer
(absolute effect size estimates based on death rate at 2 years) Follow‐up: 2 years MCID: 3% absolute difference |
328 (1 RCT) | ⊕⊝⊝⊝ Very lowa,d | HR 0.98 (0.02 to 49.40) | Low | |
| 6 per 1000f | 0 fewer per 1000 (6 fewer to 251 more) | ||||
|
Time to death from any cause (absolute effect size estimates based on death rate at 4 years) Follow‐up: range 2–4 years MCID: 3% absolute difference |
734 (2 RCTs) | ⊕⊝⊝⊝ Very lowa,d | HR 0.62 (0.39 to 1.00) | Low | |
| 121 per 1000 e | 44 fewer per 1000 (72 fewer to 0 fewer) | ||||
|
Grade I or II adverse events
assessed with:
1 study: measured as serious adverse events; 1 study: CTCAE version 3.0 and version 4.0 Follow‐up: range 1–3 months MCID: 5% absolute difference |
668 (2 RCTs) | ⊕⊕⊝⊝ Lowa,c | RR 1.13 (0.87 to 1.45) | Study population | |
| 246 per 1000 | 32 more per 1000 (32 fewer to 111 more) | ||||
| Disease‐specific quality of life | Not reported | — | — | — | — |
| *The risk in the intervention group (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). CI: confidence interval; CTCAE: Common Terminology Criteria for Adverse Events; HR: hazard ratio; MCID: minimal clinically important difference; n: number of participants; RCT: randomized controlled trial; RR: risk ratio. | |||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | |||||
aDowngraded one level for study limitations: high risk of selective reporting and other bias.
bNot downgraded further for moderate inconsistency; this contributed to the decision to downgrade twice overall.
cDowngraded one level for imprecision: confidence intervals crossed a clinically important threshold and no effect.
dDowngraded two levels for imprecision: confidence intervals crossed a clinically important threshold and no effect; wide confidence intervals
eBaseline risk for recurrence, progression, and death from any cause came from Messing 2018.
fBaseline risk for death from bladder cancer come from Böhle 2009.