Radiation dose escalation combined with hormone therapy improves outcome in localised prostate cancer

Figures & data

Table I.  Clinical characteristics and treatment of the 494 patients.

Factor (median)	All patients	Group 1 (64 Gy)	Group 2 (6 Gy)	Group 3 (70 Gy)	p-value
No. of patients	494	140	104	250
Age (y)	67 (47–85)	68 (54–85)	66 (51–76)	67 (47–77)	<0.001^a
iPSA (ng/ml)	15.4 (0.5–298)	20.5 (0.5–298)	20.8 (3–170)	13.1 (1.1–87)	<0.001^b
T stage					0.006^c
T1	102 (21%)	16 (12%)	14 (13%)	71 (29%)
T2	180 (36%)	66 (47%)	38 (37%)	76 (30%)
T3	208 (42%)	58 (41%)	50 (48%)	100 (40%)
Tx	5 (1%)		2 (2%)	3 (1%)
Histological grade (WHO)					0.97^c
well diff.	91 (30%)	42 (30%)	35 (34%)	15 (26%)
moderately diff.	162 (54%)	73 (52%)	56 (54%)	33 (57%)
poorly diff.	48 (16%)	25 (18%)	13 (12%)	10 (17%)
Gleason score
4–6	100 (52%)
7	61 (32%)			61 (32%)
8–10	31 (16%)			31 (16%)
Treatment					<0.001^c
EBRT	91 (18%)	74 (53%)	17 (16%)
EBRT + HT	403 (82%)	66 (47%)	87 (84%)	250 (100%)

iPSA = pretreatment PSA level, log scale; EBRT = external beam radiation therapy; HT = hormonal therapy;

^aOne-way ANOVA; ^bOne-way ANOVA for log-transformed iPSA; ^cLinear by linear association test.

Table II.  Outcome.

	All patients	Group 1	Group 2	Group 3
Clinical progression (PD)	91 (18%)	60 (43%)	16 (15%)	15 (6%)
Type of first progression
- local	27 (5%)	25 (18%)	3 (3%)	3 (1%)
- distant	58 (12%)	35 (25%)	13 (12%)	12 (5%)
Time to PD (months)*	35 (4–149)	39 (5–149)	28 (19–74)	30 (4–48)
Status 05.05.2004
Alive & no-BF	340	51	72	217
Dead	134	79	27	28
of prostate cancer	64 (13%)	45 (32%)	11 (11%)	9 (4%)
of other diseases	70 814%)	34 (24%)	16 (15%)	19 (8%)
PSA relapse (nadir + 2)	175 (35%)	97 (69%)	39 (37%)	39 (15%)
Time to PSA relapse (months)*	29 (4–150)	29 (4–150)	36 (5–80)	28 (4–66)
Follow up (months)*	68 (2–171)	107 (2–171)	81 (13–131)	61 (8–135)
CSS–5 years	92%	84%	94%	96%
CSS–10 years	75%	66%

* = median; BF = biochemical failure; CSS = cancer specific survival.

Figure 1.  PSA free survival.

Table III.  Results from univariate and multivariate Cox regression, assessing influence of different parameters on PSA recurrence.

Parameter	p (univariate)	p (multivariate)	HR	95% CI
Age	1.0	–
Clinical T-stage	<0.001	p=0.001
T1			Ref
T2		p=0.8	1.08	0.63 to 1.86
T3		p=0.02	1.90	1.13 to 3.20
iPSA	<0.001	p<0.001	1.41	1.20 to 1.66
Histological Grade	<0.001	p<0.001
well diff.			Ref.
moderately diff.		p=0.004	1.75	1.20 to 2.55
poorly diff.		p<0.001	3.58	2.27 to 5.64
Radiation dose	<0.001	p=0.001
64 Gy			Ref.
66 Gy		p=0.06	0.67	0.44 to 1.02
70 Gy		p<0.001	0.40	0.25 to 0.64
Hormone therapy	<0.001	p<0.001
+			Ref.
−			3.02	2.05 to 4.46
Year of treatment	<0.001	NS

Note. The covariates with p > 0.25 from the univariate analyses were used in the multivariate analyses.

Abbreviations: HR, hazard ratio; CI, confidence intervals; NS, not significant; iPSA, pretreatment PSA level, log scale.

Figure 2.  Overall survival stratified by groups.

Table IV.  Results from univariate and multivariate Cox regression, assessing influence of different parameters on overall survival.

Parameter	p (univariate)	p (multivariate)	HR	95% CI
Age	0.18	NS
Clinical T-stage	0.2	p=0.03
T1			Ref.
T2		p=0.16	0.68	0.39 to 1.17
T3		p=0.6	1.14	0.68 to 1.89
iPSA	0.4	NS
Histological grade	<0.001	p=0.001
well diff.			Ref.
moderately diff.		p=0.02	1.69	1.09 to 2.63
poorly diff.		p<0.001	2.77	1.65 to 4.65
Radiation dose	<0.001	p=0.04
64 Gy			Ref.
66 Gy		p=0.2	0.74	0.45 to 1.21
70 Gy		p=0.01	0.50	0.29 to 0.85
Hormone therapy	0.01	p=0.05
+			Ref.
−			1.50	0.99 to 2.26
Year of treatment	0.001	NS

Note. The covariates with p > 0.25 from the univariate analyses were used in the multivariate analyses.

Abbreviations: HR, hazard ratio; CI, confidence intervals; NS, not significant; iPSA, pretreatment PSA level, log scale.

Figure 3a.  Cancer specific survival stratified by groups.

Figure 3b.  Cancer specific survival in patients receiving both EBRT and HT, stratified by radiation.

Table V.  Results from univariate and multivariate Cox regression, assessing influence of different parameters on cancer specific survival.

Parameter	p (univariate)	p (multivariate)	HR	95% CI
Age	0.9	NS
Clinical T-stage	<0.001	p=0.001
T1			Ref.
T2		p=0.8	0.88	0.32 to 2.46
T3		p=0.04	2.60	1.02 to 6.65
iPSA	0.04	NS
Histological grade	<0.001	p<0.001
well diff.			Ref.
moderately diff.		p=0.007	2.89	1.33 to 6.26
poorly diff.		p<0.001	6.70	2.89 to 15.54
Radiation dose	<0.001	p=0.07
64 Gy			Ref.
66 Gy		p=0.2	0.62	0.29 to 1.32
70 Gy		p=0.03	0.38	0.16 to 0.89
Hormone therapy	<0.001	p=0.003
+			Ref.
−			2.40	1.35 to 4.26
Year of treatment	<0.001	NS

Note. The covariates with p > 0.25 from the univariate analyses were used in the multivariate analyses.

Abbreviations: HR, hazard ratio; CI, confidence intervals; NS, not significant; iPSA, pretreatment PSA level, log scale.