Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study

Figures & data

Figure 1. CONSORT diagram.

Figure 2. First event of conversion from AA to GnRH agonist, death from other causes or death from PCa assessed in competing risk analyses among men who started on anti-androgen monotherapy (AA) in competing risk analyses.

Table 1. Baseline characteristics of men in PCBaSe 3.0 diagnosed with high-risk and regionally metastatic prostate cancer in 2006–2012 and treated with anti-androgen monotherapy or GnRH agonists.

	Raw				Imputed*				Propensity score matched
	Anti-androgens (n = 2078)		GnRH agonists (n = 4878)		Anti-androgens (n = 2060)		GnRH agonists (n = 4740)		Anti-androgens (n = 1975)		GnRH agonists (n = 1975)
	n	%	n	%	n	%	n	%	n	%	n	%
Year of diagnosis
2006–2007	542	26.1	1692	34.7	538	26.1	1638	34.6	527	26.7	547	27.7
2008–2010	559	26.9	1476	30.3	548	26.6	1415	29.9	532	26.9	532	26.9
2011–2012	977	47.0	1710	35.1	974	47.3	1687	35.6	916	46.4	896	45.4
Age at diagnosis, years
<70	328	15.8	699	14.3	327	15.9	681	14.4	311	15.7	357	18.1
70–74	414	19.9	751	15.4	409	19.9	735	15.5	382	19.3	342	17.3
75–79	688	33.1	1287	26.4	682	33.1	1247	26.3	654	33.1	548	27.7
80–84	470	22.6	1367	28.0	464	22.5	1323	27.9	454	23.0	485	24.6
85–90	178	8.6	774	15.9	178	8.6	754	15.9	174	8.8	243	12.3
Mode of detection
Screening	562	27.1	933	19.1	575	27.9	936	19.7	536	27.1	510	25.8
LUTS	1016	48.9	2836	58.2	1045	50.7	2852	60.2	1021	51.7	1058	53.6
Symptoms	431	20.8	966	19.8	440	21.4	952	20.1	418	21.2	407	20.6
Missing	67	3.2	139	2.9
Clinical tumour category
T1a	3	0.1	13	0.3	3	0.1	13	0.3	3	0.2	2	0.1
T1b	29	1.4	66	1.4	30	1.5	66	1.4	30	1.5	28	1.4
T1c	374	18.0	640	13.1	375	18.2	639	13.5	342	17.3	335	17.0
T2	639	30.8	1634	33.5	645	31.3	1612	34.0	629	31.8	652	33.0
T3	937	45.1	2207	45.2	932	45.2	2157	45.5	897	45.4	882	44.7
T4	76	3.7	262	5.4	75	3.6	253	5.3	74	3.7	76	3.8
TX	20	1.0	56	1.1
N stage
N0	150	7.2	262	5.4	150	7.3	263	5.5	145	7.3	133	6.7
N1	66	3.2	211	4.3	66	3.2	207	4.4	66	3.3	64	3.2
NX	1857	89.4	4392	90.0	1844	89.5	4270	90.1	1764	89.3	1778	90.0
Missing	5	0.2	13	0.3
Gleason Grade Group
GGG1	269	12.9	382	7.8	274	13.3	394	8.3	254	12.9	221	11.2
GGG2	412	19.8	652	13.4	444	21.6	725	15.3	415	21.0	385	19.5
GGG3	409	19.7	846	17.3	433	21.0	908	19.2	410	20.8	410	20.8
GGG4	547	26.3	1273	26.1	564	27.4	1308	27.6	552	27.9	568	28.8
GGG5	328	15.8	1377	28.2	345	16.7	1405	29.6	344	17.4	391	19.8
Missing	113	5.4	348	7.1
Percent positive biopsy cores
0–49%	452	21.8	623	12.8	570	27.7	838	17.7	528	26.7	507	25.7
50–74%	459	22.1	777	15.9	562	27.3	1049	22.1	526	26.6	499	25.3
75–100%	733	35.3	2121	43.5	928	45.0	2853	60.2	921	46.6	969	49.1
Missing	434	20.9	1357	27.8
PSA at diagnosis, ng/ml
<3	22	1.1	44	0.9	23	1.1	43	0.9	23	1.2	18	0.9
3–10	238	11.5	483	9.9	238	11.6	477	10.1	223	11.3	230	11.6
10–20	387	18.6	846	17.3	388	18.8	840	17.7	376	19.0	376	19.0
20–50	993	47.8	2151	44.1	988	48.0	2111	44.5	936	47.4	936	47.4
50+	423	20.4	1277	26.2	423	20.5	1269	26.8	417	21.1	415	21.0
Missing	15	0.7	77	1.6
Charlson comorbidity index
0	1217	58.6	2702	55.4	1206	58.5	2618	55.2	1148	58.1	1168	59.1
1	506	24.4	1153	23.6	501	24.3	1124	23.7	486	24.6	459	23.2
2	208	10.0	577	11.8	206	10.0	565	11.9	199	10.1	205	10.4
3+	147	7.1	446	9.1	147	7.1	433	9.1	142	7.2	143	7.2
Marital status
Married	1388	66.8	3057	62.7	1375	66.7	2969	62.6	1315	66.6	1335	67.6
Not married	690	33.2	1821	37.3	685	33.3	1771	37.4	660	33.4	640	32.4
Education level
High	392	18.9	679	13.9	394	19.1	670	14.1	367	18.6	335	17.0
Middle	716	34.5	1590	32.6	717	34.8	1564	33.0	682	34.5	689	34.9
Low	948	45.6	2532	51.9	949	46.1	2506	52.9	926	46.9	951	48.2
Missing	22	1.1	77	1.6

*Results obtained after imputation of missing values and following matching on propensity score.  Results from the first imputed dataset presented.

Figure 3. Cumulative probability of death from PCa or death from other causes for men on anti-androgen monotherapy (AA) and men on GnRH agonists.

Table 2. Risk of death from prostate cancer or death from all causes in men on primary anti-androgen monotherapy or GnRH agonists.

	All men with high-risk and regionally metastatic prostate cancer				Men with high-risk* prostate cancer					Men with regionally metastatic** prostate cancer
	Death from prostate cancer		Death from all causes		Death from prostate cancer			Death from all causes		Death from prostate cancer			Death from all causes
	HR	95% CI	HR	95% CI	HR	95% CI		HR	95% CI	HR	95% CI		HR	95% CI
Anti-androgen monotherapy	1.00	ref	1.00	ref	1.00	ref		1.00	ref	1.00	ref		1.00	ref
GnRH agonists
Crude model using age as time scale	1.39	1.23–1.57	1.45	1.34–1.57	1.45	1.24–1.69	1.50		1.37–1.65	1.16		0.96–1.42	1.26	1.09–1.46
Adjustment
T stage	1.37	1.21–1.55	1.45	1.34–1.57	1.44	1.23–1.68	1.51		1.37–1.66	1.16		0.95–1.41	1.26	1.09–1.46
Gleason Grade Group	1.21	1.07–1.37	1.37	1.27–1.48	1.25	1.07–1.47	1.44		1.30–1.58	1.06		0.87–1.29	1.19	1.03–1.37
PSA***	1.19	1.05–1.34	1.36	1.25–1.47	1.24	1.06–1.46	1.43		1.30–1.57	1.04		0.85–1.27	1.18	1.02–1.36
Proportion positive biopsy cores****	1.15	1.01–1.30	1.34	1.23–1.45	1.19	1.01–1.39	1.40		1.27–1.55	1.02		0.84–1.25	1.17	1.01–1.35
Imaging performed	1.11	0.98–1.25	1.29	1.19–1.40	1.15	0.98–1.34	1.36		1.23–1.50	0.96		0.79–1.18	1.11	0.96–1.29
Time between diagnosis and start of treatment	1.11	0.98–1.26	1.29	1.19–1.40	1.15	0.98–1.35	1.36		1.23–1.50	0.97		0.79–1.18	1.11	0.95–1.28
Mode of detection	1.10	0.97–1.25	1.28	1.18–1.39	1.13	0.96–1.33	1.34		1.21–1.48	0.96		0.78–1.18	1.10	0.95–1.28
Year of diagnosis	1.09	0.96–1.23	1.27	1.17–1.38	1.12	0.95–1.31	1.33		1.20–1.47	0.96		0.78–1.17	1.10	0.95–1.28
CCI	1.08	0.96–1.23	1.25	1.15–1.36	1.11	0.95–1.31	1.30		1.18–1.43	0.96		0.78–1.17	1.10	0.95–1.27
Marital status	1.08	0.96–1.23	1.24	1.14–1.35	1.11	0.95–1.31	1.29		1.17–1.43	0.96		0.78–1.17	1.09	0.94–1.26
Education	1.08	0.95–1.23	1.23	1.13–1.34	1.11	0.94–1.31	1.28		1.16–1.41	0.96		0.78–1.17	1.09	0.94–1.26

Hazard ratios calculated by use of Cox regression analyses.

*High-risk prostate cancer: T3 and/or PSA 20 ng/ml or higher and lower than 50 ng/ml and/or Gleason Grade Group 4–5.

**Regionally metastatic prostate cancer: T4 and/or PSA 50 ng/ml or higher and lower than 100 ng/ml or N1.

***Modelled using a linear spline with knots in PSA 3, 10, 20 and 50.

****Modelled as an interaction with T stage in men not diagnosed following TUR-P.

Figure 4. Probability of PCa death and death from all causes following propensity score matched for men on anti-androgen monotherapy (AA) and GnRH agonists, assessed with 1-Kaplan-Meier estimates.

Table 3. Risk of death from prostate cancer or death from all causes for men on primary GnRH agonists or anti-androgen monotherapy (AA, reference in analyses) following propensity score matching.

	Including all men with a match
	Number of men in group*	No of events		Crude		Adjusted
		AA	GnRH	HR	95% CI	HR	95% CI
High-risk and regionally metastatic prostate cancer
Death from prostate cancer	1975	348	371	1.09	0.94–1.26	1.05	0.90–1.23
Death from all causes	1975	702	858	1.25	1.13–1.38	1.23	1.11–1.36
High-risk prostate cancer**
Death from prostate cancer	1436	209	239	1.15	0.91–1.45	1.12	0.88–1.42
Death from all causes	1436	473	619	1.33	1.18–1.50	1.29	1.14–1.46
Regionally metastatic prostate cancer***
Death from prostate cancer	506	132	123	0.96	0.72–1.28	0.93	0.69–1.43
Death from all causes	506	215	237	1.11	0.89–1.37	1.12	0.89–1.40

Hazard ratios calculate by use of Cox regression analyses. The median time from diagnosis to start of treatment was 16 days longer for men on AA compared to men on GnRH agonists.

*Number of men in the first of the imputed dataset.

**High-risk prostate cancer: T3 and/or PSA 20 ng/ml or higher and lower than 50 ng/ml and/or Gleason Grade Group 4–5.

***Regionally metastatic prostate cancer: T4 and/or PSA 50 ng/ml or higher and lower than 100 ng/ml or N1.