Temporal patterns of late bowel and bladder radiotherapy toxicity in a randomised controlled trial assessing duration of neo-adjuvant hormones in prostate cancer

Figures & data

Table I. Randomised trial ICORG 97-01: Neo-adjuvant hormone therapy prior to radiation. Pre-treatment characteristics*.

	Analysis of late toxicity (n = 241)
Age (years) Mean Median	66.3 67.3
Age group ≤ 60 61–65 66–70 > 70	41 (17%) 49 (20%) 110 (46%) 41 (17%)
KPS 70 80 90 100	3 (1%) 28 (12%) 180 (75%) 30 (12%)
PSA^† Median ug/L Range ug/L PSA^† group ≤ 10 10·1–20 > 20	14.5 0.6–263 73 (30%) 79 (33%) 89 (37%)
Gleason score < 7 = 7 > 7	102 (42%) 106 (44%) 33 (14%)
T Stage T1 T2 T3 T4	25 (10%) 68 (28%) 132 (55%) 16 (7%)
Risk stratification (protocol) Intermediate High Risk group (NCCN) Intermediate High Very high	131 (54%) 110 (46%) 45 (19%) 120 (50%) 76 (31%)
Co-morbidities CAD/HTN Hip replacement Diverticulitis Diabetes	78 (32%) 17 (7%) 5 (2%) 22 (9%)

* Data are number of patients unless otherwise stated; ^† PSA refers to the last PSA result before the start of hormone therapy. CAD/HTN, Coronary artery disease/hypertension.

Figure 1. Cumulative incidence of late gastrointestinal and genitourinary toxicity.

Figure 2. Prevalence of late Grade 2 + toxicity after RT for prostate cancer.

Figure 3. Time to final resolution of late Grade 2 + gastrointestinal toxicity.

Figure 4. Time to final resolution of late Grade 2 + genitourinary toxicity.

Table II. Acute by late GI and GU toxicity.

Acute GI grade	Late GI grade (percentage of late that was also acute)					Total
	0	1	2	3	4
0	65 (56%)	36 (39%)	6 (24%)	3 (100%)	0 (0%)	110 (46%)
1	32 (28%)	38 (41%)	12 (48%)	0 (0%)	0 (0%)	82 (35%)
2	19 (16%)	18 (20%)	7 (28%)	0 (0%)	1 (100%)	45 (19%)
Total	116	92	25	3	1	237

Acute GU grade	Late GU grade (percentage of late that was also acute)					Total
	0	1	2	3	4
0	27 (23%)	8 (10%)	9 (24%)	0 (0%)	0 (0%)	44 (19%)
1	51 (44%)	42 (51%)	16 (42%)	1 (50%)	0 (0%)	110 (46%)
2	33 (28%)	27 (33%)	9 (24%)	0 (0%)	0 (0%)	69 (29%)
3	4 (3%)	5 (6%)	4 (10%)	1 (50%)	0 (0%)	14 (6%)
4	1 (1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (0.4%)
Total	116	82	38	2	0	238

Note: This table only includes those patients for whom we had both an acute toxicity assessment and a late toxicity assessment. GI + GU: For 5 patients we had an acute assessment but no late assessment and for 3 patients we had a late assessment but no acute assessment. GI: For another patient we had an acute assessment but no late assessment.

Table III. Cox regression analysis of late bowel toxicity (n = 253).

		Univariate analysis			Multivariate analysis
Covariate	Ref. category	HR	95% CI	p	HR	95% CI	p
Acute bowel toxicity	No toxicity	1.36	1.08–1.70	0.008
Acute bowel toxicity Grade 1 Grade 2	No toxicity	1.801 1.730	1.20–2.70 1.07–2.81	0.009 0.004 0.026
KPS 90-100	KPS 70-80	1.28	0.80–2.07	0.310
Acute bladder toxicity	No toxicity	1.28	1.05–1.57	0.015	1.27	1.03–1.56	0.025
Acute bladder toxicity Grade 1 Grade 2 Grade 3-4	No toxicity	1.628 1.985 2.315	0.95–2.80 1.11–3.54 1.06–5.06	0.086 0.077 0.020 0.036
KPS 90-100	KPS 70-80	1.87	1.19–2.92	0.006	1.34	1.07–1.68	0.010

CI, confidence interval; HR, hazard ratio or relative risk.

Table IV. Cumulative incidence of late RTOG grade ≥ 2 toxicity in five randomized trials.

	Trial [Reference]
	MD Anderson [23]	NKI [14–16]	PROG 9509 [20]	RMH pilot [24]	MRC RT01 [11,12]
RT dose Gy	70	68	70.2	74	74
Setting	US	The Netherlands	US	UK	UK, Australia, New Zealand
Sites	Single site	Multisite	Single site	Single site	Multisite
No. of patients	301	669	393	126	843
Toxicity scale	RTOG-LENT modified∗	RTOG/EORTC	RTOG	RTOG original	RTOG original
Median follow-up (years)	8.7	5.8	5.5	6.2	5.3
Grade ≥ 2	13%	25%	9%	23%	33%
Analysis time point and type Resolved toxicity	By 10 years cumulative No data	By 7 years cumulative xx	“Late” snapshot No data	By 2 years cumulative No data	By 5 years cumulative @

∗Composite score including rectal bleeding. xx, The incidence of rectal bleeding stabilized after 5 years, with no new cases observed after 5 years. The incidence of faecal incontinence did not stabilize.

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