Comparison 1. Non‐steroidal antiandrogen monotherapy versus LHRH agonists or surgical castration monotherapy.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival	6		Hazard Ratio (Random, 95% CI)	Subtotals only
1.1 Total	6	2712	Hazard Ratio (Random, 95% CI)	1.24 [1.05, 1.48]
1.2 Subgroup analysis: non‐metastatic disease	2	608	Hazard Ratio (Random, 95% CI)	1.00 [0.79, 1.26]
1.3 Subgroup analysis: metastatic disease	5	2103	Hazard Ratio (Random, 95% CI)	1.34 [1.14, 1.57]
1.4 Subgroup analysis: bicalutamide 50 mg daily	3	1196	Hazard Ratio (Random, 95% CI)	1.45 [1.19, 1.75]
1.5 Subgroup analysis: bicalutamide 150 mg daily	2	1288	Hazard Ratio (Random, 95% CI)	1.18 [0.96, 1.45]
1.6 Subgroup analysis: bicalutamide 450 mg daily or 600 mg daily	1	228	Hazard Ratio (Random, 95% CI)	0.88 [0.62, 1.25]
1.7 Subgroup analysis: non‐metastatic disease and bicalutamide 150 mg daily	1	480	Hazard Ratio (Random, 95% CI)	1.05 [0.81, 1.36]
1.8 Subgroup analysis: non‐metastatic disease and bicalutamide 450 mg daily or 600 mg daily	1	128	Hazard Ratio (Random, 95% CI)	0.79 [0.46, 1.36]
1.9 Subgroup analysis: metastatic disease and bicalutamide 50 mg daily	3	1196	Hazard Ratio (Random, 95% CI)	1.45 [1.19, 1.75]
1.10 Subgroup analysis: metastatic disease and bicalutamide 150 mg daily	1	808	Hazard Ratio (Random, 95% CI)	1.30 [1.04, 1.63]
1.11 Subgroup analysis: metastatic disease and bicalutamide 450 mg daily or 600 mg daily	1	99	Hazard Ratio (Random, 95% CI)	0.91 [0.56, 1.48]
2 Cancer‐specific mortality	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 Total	3	904	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.86, 2.05]
2.2 Total after a minimum 12 months	2	680	Risk Ratio (M‐H, Random, 95% CI)	1.63 [0.71, 3.73]
2.3 Total after median 5 years	1	224	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.73, 1.47]
3 Treatment discontinuation due to adverse events	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.1 Total	8	1559	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [1.13, 2.94]
3.2 Subgroup analysis: non‐metastatic disease	3	194	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.66, 3.28]
3.3 Subgroup analysis: metastatic disease	4	1141	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.54, 3.54]
3.4 Subgroup analysis: bicalutamide 50 mg daily	3	1037	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.29, 2.56]
3.5 Subgroup analysis: bicalutamide 150 mg daily	3	194	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.66, 3.28]
3.6 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	8.35 [0.46, 151.19]
3.7 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	2.66 [1.17, 6.01]
3.8 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	2.45 [0.95, 6.31]
4 Clinical progression	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
4.1 Total at 1 year	5	2067	Risk Ratio (M‐H, Random, 95% CI)	1.25 [1.08, 1.45]
4.2 Total at 70 weeks	6	2373	Risk Ratio (M‐H, Random, 95% CI)	1.26 [1.08, 1.45]
4.3 Total at 2 years	3	1336	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.04, 1.25]
4.4 Total at 3 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.87, 1.23]
4.5 Total at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.91, 1.26]
4.6 Total at 5 years	2	698	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.88, 1.06]
4.7 Subgroup analysis: non‐metastatic disease at 1 year	2	528	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.82, 1.96]
4.8 Subgroup analysis: non‐metastatic disease at 70 weeks	2	528	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.83, 1.68]
4.9 Subgroup analysis: non‐metastatic disease at 2 years	2	528	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.81, 1.31]
4.10 Subgroup analysis: non‐metastatic disease at 3 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.87, 1.23]
4.11 Subgroup analysis: non‐metastatic disease at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.91, 1.26]
4.12 Subgroup analysis: non‐metastatic disease at 5 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.88, 1.06]
4.13 Subgroup analysis: metastatic disease at 1 year	3	1539	Risk Ratio (M‐H, Random, 95% CI)	1.25 [1.05, 1.49]
4.14 Subgroup analysis: metastatic disease at 70 weeks	4	1845	Risk Ratio (M‐H, Random, 95% CI)	1.27 [1.07, 1.51]
4.15 Subgroup analysis: metastatic disease at 2 years	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.17 [1.05, 1.29]
4.16 Subgroup analysis: bicalutamide 50 mg daily at 1 year	2	731	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.91, 1.76]
4.17 Subgroup analysis: bicalutamide 50 mg daily at 70 weeks	3	1037	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.99, 1.71]
4.18 Subgroup analysis: bicalutamide 150 mg daily at 1 year	3	1336	Risk Ratio (M‐H, Random, 95% CI)	1.25 [1.07, 1.46]
4.19 Subgroup analysis: bicalutamide 150 mg daily at 70 weeks	3	1336	Risk Ratio (M‐H, Random, 95% CI)	1.22 [1.07, 1.39]
4.20 Subgroup analysis: bicalutamide 150 mg daily at 2 years	3	1336	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.04, 1.25]
4.21 Subgroup analysis: bicalutamide 150 mg daily at 3 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.87, 1.23]
4.22 Subgroup analysis: bicalutamide 150 mg daily at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.91, 1.26]
4.23 Subgroup analysis: bicalutamide 150 mg daily at 5 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.88, 1.06]
4.24 Subgroup analysis: bicalutamide 450 mg daily at 5 years	1	177	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.54, 1.86]
4.25 Subgroup analysis: bicalutamide 600 mg daily at 5 years	1	127	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.33, 1.86]
5 Clinical progression (with imputed event numbers)	7		Risk Ratio (Fixed, 95% CI)	Subtotals only
5.1 Total (with imputed event numbers) at 1 year	5	2167	Risk Ratio (Fixed, 95% CI)	1.43 [1.16, 1.76]
5.2 Total (with imputed event numbers) at 70 weeks	6	2543	Risk Ratio (Fixed, 95% CI)	1.43 [1.19, 1.73]
5.3 Total (with imputed event numbers) at 2 years	3	1347	Risk Ratio (Fixed, 95% CI)	1.39 [1.09, 1.78]
5.4 Total (with imputed event numbers) at 5 years	2	708	Risk Ratio (Fixed, 95% CI)	0.86 [0.56, 1.31]
5.5 Subgroup analysis: non‐metastatic disease (with imputed event numbers) at 1 year	2	539	Risk Ratio (Fixed, 95% CI)	1.33 [0.80, 2.22]
5.6 Subgroup analysis: non‐metastatic disease (with imputed event numbers) at 70 weeks	2	539	Risk Ratio (Fixed, 95% CI)	1.23 [0.78, 1.94]
5.7 Subgroup analysis: non‐metastatic disease (with imputed event numbers) at 2 years	2	539	Risk Ratio (Fixed, 95% CI)	1.05 [0.71, 1.55]
5.8 Subgroup analysis: non‐metastatic disease (with imputed event numbers) at 5 years	1	480	Risk Ratio (Fixed, 95% CI)	0.84 [0.52, 1.36]
5.9 Subgroup analysis: metastatic disease (with imputed event numbers) at 1 year	3	1628	Risk Ratio (Fixed, 95% CI)	1.45 [1.16, 1.82]
5.10 Subgroup analysis: metastatic disease (with imputed event numbers) at 70 weeks	4	2004	Risk Ratio (Fixed, 95% CI)	1.48 [1.20, 1.83]
5.11 Subgroup analysis: metastatic disease (with imputed event numbers) at 2 years	1	808	Risk Ratio (Fixed, 95% CI)	1.69 [1.22, 2.32]
5.12 Subgroup analysis: bicalutamide 50 mg daily (with imputed event numbers) at 1 year	2	820	Risk Ratio (Fixed, 95% CI)	1.40 [0.99, 1.98]
5.13 Subgroup analysis: bicalutamide 50 mg daily (with imputed event numbers) at 70 weeks	3	1196	Risk Ratio (Fixed, 95% CI)	1.40 [1.04, 1.88]
5.14 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 1 year	3	1347	Risk Ratio (Fixed, 95% CI)	1.45 [1.12, 1.87]
5.15 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 70 weeks	3	1347	Risk Ratio (Fixed, 95% CI)	1.46 [1.14, 1.87]
5.16 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 2 years	3	1347	Risk Ratio (Fixed, 95% CI)	1.39 [1.09, 1.78]
5.17 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 5 years	1	480	Risk Ratio (Fixed, 95% CI)	0.84 [0.52, 1.36]
5.18 Subgroup analysis: bicalutamide 450 mg daily (with imputed event numbers) at 5 years	1	185	Risk Ratio (Fixed, 95% CI)	1.00 [0.41, 2.47]
5.19 Subgroup analysis: bicalutamide 600 mg daily (with imputed event numbers) at 5 years	1	133	Risk Ratio (Fixed, 95% CI)	0.78 [0.27, 2.25]
6 Biochemical progression	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.1 Total at 1 year	2	99	Risk Ratio (M‐H, Fixed, 95% CI)	3.12 [0.13, 73.06]
6.2 Total at 2 years	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Total at 3 years	1	86	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.94, 1.26]
7 Biochemical progression (with imputed event numbers)	3		Risk Ratio (Fixed, 95% CI)	Subtotals only
7.1 Total (with imputed event numbers) at 1 year	2	110	Risk Ratio (Fixed, 95% CI)	2.29 [0.15, 34.62]
7.2 Total (with imputed event numbers) at 2 years	1	59	Risk Ratio (Fixed, 95% CI)	0.96 [0.00, 196.72]
7.3 Total (with imputed event numbers) at 3 years	1	104	Risk Ratio (Fixed, 95% CI)	1.07 [0.72, 1.58]
8 Treatment failure	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
8.1 Total at 1 year	3	1539	Risk Ratio (M‐H, Random, 95% CI)	1.19 [1.02, 1.38]
8.2 Total at 70 weeks	4	1845	Risk Ratio (M‐H, Random, 95% CI)	1.27 [1.05, 1.52]
8.3 Total at 2 years	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.05, 1.24]
8.4 Total at 3 years	1	86	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.63, 3.99]
8.5 Total at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.93, 1.16]
8.6 Subgroup analysis: non‐metastatic disease at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.93, 1.16]
8.7 Subgroup analysis: metastatic disease at 1 year	3	1539	Risk Ratio (M‐H, Random, 95% CI)	1.19 [1.02, 1.38]
8.8 Subgroup analysis: metastatic disease at 70 weeks	4	1845	Risk Ratio (M‐H, Random, 95% CI)	1.27 [1.05, 1.52]
8.9 Subgroup analysis: metastatic disease at 2 years	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.05, 1.24]
8.10 Subgroup analysis: metastatic disease at 3 years	1	86	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.63, 3.99]
8.11 Subgroup analysis: bicalutamide 50 mg daily at 1 year	2	731	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.90, 1.57]
8.12 Subgroup analysis: bicalutamide 50 mg daily at 70 weeks	3	1037	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.98, 1.75]
8.13 Subgroup analysis: bicalutamide 150 mg daily at 1 year	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.17 [1.01, 1.35]
8.14 Subgroup analysis: bicalutamide 150 mg daily at 70 weeks	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.18 [1.05, 1.34]
8.15 Subgroup analysis: bicalutamide 150 mg daily at 2 years	1	808	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.05, 1.24]
8.16 Subgroup analysis: bicalutamide 150 mg daily at 4 years	1	480	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.93, 1.16]
8.17 Subgroup analysis: flutamide 250 mg 3 times daily at 3 years	1	86	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.63, 3.99]
9 Treatment failure (with imputed event numbers)	5		Risk Ratio (Fixed, 95% CI)	Subtotals only
9.1 Total (with imputed event numbers) at 1 year	3	1628	Risk Ratio (Fixed, 95% CI)	1.19 [1.06, 1.35]
9.2 Total (with imputed event numbers) at 70 weeks	4	2004	Risk Ratio (Fixed, 95% CI)	1.21 [1.09, 1.35]
9.3 Total (with imputed event numbers) at 3 years	1	104	Risk Ratio (Fixed, 95% CI)	1.51 [0.32, 7.06]
9.4 Subgroup analysis: metastatic disease (with imputed event numbers) at 1 year	3	1628	Risk Ratio (Fixed, 95% CI)	1.19 [1.06, 1.35]
9.5 Subgroup analysis: metastatic disease (with imputed event numbers) at 70 weeks	4	2004	Risk Ratio (Fixed, 95% CI)	1.21 [1.09, 1.35]
9.6 Subgroup analysis: metastatic disease (with imputed event numbers) at 3 years	1	104	Risk Ratio (Fixed, 95% CI)	1.51 [0.32, 7.06]
9.7 Subgroup analysis: bicalutamide 50 mg daily (with imputed event numbers) at 1 year	2	820	Risk Ratio (Fixed, 95% CI)	1.27 [1.01, 1.60]
9.8 Subgroup analysis: bicalutamide 50 mg daily (with imputed event numbers) at 70 weeks	3	1196	Risk Ratio (Fixed, 95% CI)	1.29 [1.05, 1.57]
9.9 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 1 year	1	808	Risk Ratio (Fixed, 95% CI)	1.17 [1.01, 1.35]
9.10 Subgroup analysis: bicalutamide 150 mg daily (with imputed event numbers) at 70 weeks	1	808	Risk Ratio (Fixed, 95% CI)	1.18 [1.05, 1.34]
9.11 Subgroup analysis: flutamide 250 mg 3 times daily (with imputed event numbers) at 3 years	1	104	Risk Ratio (Fixed, 95% CI)	1.51 [0.32, 7.06]
10 Breast pain	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
10.1 Total	7	2670	Risk Ratio (M‐H, Fixed, 95% CI)	22.97 [14.79, 35.67]
10.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Fixed, 95% CI)	19.39 [10.26, 36.66]
10.3 Subgroup analysis: bicalutamide 150 mg daily	3	1420	Risk Ratio (M‐H, Fixed, 95% CI)	25.82 [13.34, 49.97]
10.4 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	23.48 [5.88, 93.73]
10.5 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	25.71 [6.37, 103.78]
11 Pelvic pain	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
11.1 Total	5	2395	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.78, 1.24]
11.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.64, 1.22]
11.3 Subgroup analysis: bicalutamide 150 mg daily	2	1369	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.79, 1.53]
12 Bone pain	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
12.1 Bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.68, 1.72]
13 Back pain	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
13.1 Total	5	1351	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.70, 1.61]
13.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.54, 1.94]
13.3 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Random, 95% CI)	2.04 [0.54, 7.71]
13.4 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.59, 1.80]
13.5 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.29, 1.57]
14 Headache	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
14.1 Total	2	584	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.24, 1.15]
14.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.20, 1.05]
14.3 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	2.78 [0.12, 66.75]
15 Abdominal pain	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
15.1 Total	3	1058	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [0.90, 2.48]
15.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.58, 2.70]
15.3 Subgroup analysis: bicalutamide 150 mg daily	1	474	Risk Ratio (M‐H, Fixed, 95% CI)	1.87 [0.92, 3.81]
15.4 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	0.31 [0.01, 7.42]
16 General pain	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
16.1 Total	4	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.80, 1.16]
16.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.65, 1.32]
16.3 Subgroup analysis: bicalutamide 150 mg daily	2	1369	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.71, 1.16]
16.4 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [0.80, 2.48]
16.5 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.67, 2.70]
17 Gynaecomastia	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
17.1 Total	8	2774	Risk Ratio (M‐H, Random, 95% CI)	8.43 [3.19, 22.28]
17.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Random, 95% CI)	14.07 [3.74, 52.85]
17.3 Subgroup analysis: bicalutamide 150 mg daily	3	1420	Risk Ratio (M‐H, Random, 95% CI)	5.01 [0.88, 28.69]
17.4 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Random, 95% CI)	3.70 [1.33, 10.33]
17.5 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Random, 95% CI)	27.88 [7.02, 110.79]
17.6 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Random, 95% CI)	20.36 [4.97, 83.40]
18 Constipation	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
18.1 Total	4	1250	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.65, 1.95]
18.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.50, 1.73]
18.3 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Random, 95% CI)	1.54 [0.84, 2.81]
18.4 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Random, 95% CI)	1.99 [1.03, 3.85]
19 Diarrhoea	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
19.1 Total	7	1929	Risk Ratio (M‐H, Random, 95% CI)	1.73 [0.80, 3.71]
19.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Random, 95% CI)	1.96 [1.00, 3.82]
19.3 Subgroup analysis: bicalutamide 150 mg daily	2	575	Risk Ratio (M‐H, Random, 95% CI)	1.29 [0.14, 12.28]
19.4 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Random, 95% CI)	8.35 [0.46, 151.19]
19.5 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Random, 95% CI)	1.35 [0.57, 3.19]
19.6 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Random, 95% CI)	2.14 [0.86, 5.32]
20 Vomiting	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
20.1 Total	3	650	Risk Ratio (M‐H, Fixed, 95% CI)	3.88 [1.38, 10.87]
20.2 Subgroup analysis: bicalutamide 50 mg daily	2	546	Risk Ratio (M‐H, Fixed, 95% CI)	3.05 [0.99, 9.35]
20.3 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	10.2 [0.58, 179.88]
21 Hypertension	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
21.1 Bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.06, 1.34]
22 Loss of sexual interest	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
22.1 Bicalutamide 150 mg daily	1	51	Risk Ratio (M‐H, Fixed, 95% CI)	0.50 [0.30, 0.83]
23 Asthenia	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
23.1 Total	4	2073	Risk Ratio (M‐H, Fixed, 95% CI)	1.77 [1.36, 2.31]
23.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	1.74 [1.11, 2.72]
23.3 Subgroup analysis: bicalutamide 150 mg daily	2	1369	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [1.10, 2.28]
23.4 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	3.07 [1.38, 6.84]
23.5 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	2.45 [0.95, 6.31]
24 Insomnia	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.1 Total	2	325	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.11, 2.37]
24.2 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.02, 1.36]
24.3 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.38, 2.06]
24.4 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.29, 2.58]
25 Hot flashes	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
25.1 Total	8	2774	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.19, 0.27]
25.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Fixed, 95% CI)	0.20 [0.15, 0.27]
25.3 Subgroup analysis: bicalutamide 150 mg daily	3	1420	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.19, 0.30]
25.4 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.10, 0.82]
25.5 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.12, 0.40]
25.6 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.31 [0.15, 0.63]
26 Night sweats	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
26.1 Total	2	1571	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.17, 0.49]
26.2 Subgroup analysis: bicalutamide 50 mg daily	1	303	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.12, 1.09]
26.3 Subgroup analysis: bicalutamide 150 mg daily	1	1268	Risk Ratio (M‐H, Fixed, 95% CI)	0.26 [0.14, 0.49]
27 Anaemia	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
27.1 Total	2	294	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.16, 5.35]
27.2 Subgroup analysis: bicalutamide 50 mg daily	1	243	Risk Ratio (M‐H, Random, 95% CI)	3.18 [0.34, 30.13]
27.3 Subgroup analysis: bicalutamide 150 mg daily	1	51	Risk Ratio (M‐H, Random, 95% CI)	0.52 [0.31, 0.88]
28 Hepatic enzyme increase	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
28.1 Total	2	205	Risk Ratio (M‐H, Fixed, 95% CI)	4.91 [0.59, 40.86]
28.2 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	7.14 [0.38, 134.72]
28.3 Subgroup analysis: flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	2.78 [0.12, 66.75]
29 Rash	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
29.1 Total	3	805	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.77, 2.16]
29.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.50, 1.92]
29.3 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	5.10 [0.62, 42.12]
29.4 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.47, 3.61]
29.5 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	1.79 [0.58, 5.52]
30 Pruritus	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
30.1 Total	2	723	Risk Ratio (M‐H, Fixed, 95% CI)	2.59 [0.93, 7.19]
30.2 Subgroup analysis: bicalutamide 50 mg daily	2	723	Risk Ratio (M‐H, Fixed, 95% CI)	2.59 [0.93, 7.19]
31 Dyspnoea	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
31.1 Bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.24, 1.31]
32 Infection	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
32.1 Total	4	2294	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.58, 1.03]
32.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.34, 0.91]
32.3 Subgroup analysis: bicalutamide 150 mg daily	1	1268	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.65, 1.33]
33 Pharyngitis	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
33.1 Total	2	325	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.47, 1.34]
33.2 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.11, 1.36]
33.3 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.56, 1.93]
33.4 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.34, 1.91]
34 Arthritis	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
34.1 Bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.12, 1.60]
35 Sinusitis	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
35.1 Bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.28 [0.36, 4.48]
36 Urinary tract infection	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
36.1 Total	2	698	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.53, 1.19]
36.2 Subgroup analysis: bicalutamide 150 mg daily	1	474	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.43, 1.14]
36.3 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.40, 1.99]
36.4 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	1.36 [0.57, 3.27]
37 Dizziness	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
37.1 Total	2	581	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.61, 1.95]
37.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.49, 1.97]
37.3 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.49, 4.20]
38 Haemorrhage	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
38.1 Total	2	546	Risk Ratio (M‐H, Fixed, 95% CI)	0.07 [0.01, 0.54]
38.2 Subgroup analysis: bicalutamide 50 mg daily	2	546	Risk Ratio (M‐H, Fixed, 95% CI)	0.07 [0.01, 0.54]
39 Haematuria	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
39.1 Total	2	954	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.14, 9.87]
39.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.26, 0.67]
39.3 Subgroup analysis: bicalutamide 150 mg daily	1	474	Risk Ratio (M‐H, Random, 95% CI)	3.49 [2.01, 6.05]
40 Nocturia	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
40.1 Bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.20, 0.69]
41 Urinary frequency	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
41.1 Bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.11, 0.47]
42 Urinary retention	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
42.1 Bicalutamide 150 mg daily	1	1268	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.55, 1.24]
43 Peripheral oedema	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
43.1 Total	2	1748	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.33, 1.15]
43.2 Subgroup analysis: bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Random, 95% CI)	0.42 [0.21, 0.82]
43.3 Subgroup analysis: bicalutamide 150 mg daily	1	1268	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.54, 1.17]
44 Anorexia	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
44.1 Bicalutamide 50 mg daily	1	480	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.57, 2.18]
45 Loss of sexual function	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
45.1 Bicalutamide 50 mg daily	1	303	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.14, 6.87]
46 Arthralgia	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
46.1 Total	1	224	Risk Ratio (M‐H, Fixed, 95% CI)	1.65 [0.86, 3.15]
46.2 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	1.96 [1.01, 3.80]
46.3 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.36, 2.63]
47 Gastralgia	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
47.1 Flutamide 250 mg 3 times daily	1	104	Risk Ratio (M‐H, Fixed, 95% CI)	2.78 [0.12, 66.75]
48 Nausea	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
48.1 Total	3	1026	Risk Ratio (M‐H, Random, 95% CI)	3.24 [0.95, 11.02]
48.2 Subgroup analysis: bicalutamide 50 mg daily	3	1026	Risk Ratio (M‐H, Random, 95% CI)	3.24 [0.95, 11.02]
49 Fatigue	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
49.1 Bicalutamide 150 mg daily	1	51	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.31, 0.88]
50 Dry skin	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
50.1 Total	1	224	Risk Ratio (M‐H, Fixed, 95% CI)	7.41 [0.42, 132.46]
50.2 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	8.81 [0.48, 161.24]
50.3 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	6.35 [0.26, 152.67]
51 Aggravation reaction	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
51.1 Bicalutamide 150 mg daily	1	474	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.45, 1.05]
52 Serious adverse events	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
52.1 Total	2	325	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.79, 1.28]
52.2 Subgroup analysis: bicalutamide 150 mg daily	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.49, 4.20]
52.3 Subgroup analysis: bicalutamide 450 mg daily	1	182	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.73, 1.25]
52.4 Subgroup analysis: bicalutamide 600 mg daily	1	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.71, 1.37]