Health-related quality of life in rectal cancer patients undergoing neoadjuvant chemoradiation with delayed surgery versus short-course radiotherapy with immediate surgery: a propensity score-matched cohort study

Figures & data

Figure 1. Flowchart of selected patients within the prospective data collection initiative on colorectal cancer (PLCRC) Utrecht rectal cancer (U-RECT) cohort treated with short-course radiotherapy with immediate surgery (SCRT-IS) or chemoradiation with delayed surgery (CRT-DS).

Table 1. Baseline characteristics before and after propensity score matching of rectal cancer patients treated with neoadjuvant short-course radiotherapy with immediate surgery (SCRT-IS) or neoadjuvant chemoradiation with delayed surgery (CRT-DS).

	Original cohort		Matched cohort^#
	SCRT-IS	CRT-DS	SCRT-IS	CRT-DS
	N = 106 (%)	N = 119 (%)	N = 78 (%)	N = 78 (%)
Age, median (range)	66 (40–85)	64 (42–83)	65 (40–83)	66 (47–83)
Sex
Male	77 (72.6)	85 (71.4)	55 (70.5)	54 (69.2)
Female	29 (27.4)	34 (28.6)	23 (29.5)	24 (30.8)
Comorbidity
>1 condition	66 (62.3)	74 (62.2)	43 (55.1)	45 (57.7)
None	40 (37.7)	45 (37.8)	35 (44.9)	33 (42.3)
Tumour location
<6cm	36 (34.0)	62 (52.1)	31 (39.7)	34 (43.6)
6-10cm	48 (45.3)	42 (35.3)	35 (44.9)	32 (41.0)
>10cm	22 (20.8)	15 (12.6)	12 (15.4)	12 (15.4)
Clinical tumor stage
cT2	34 (32.1)	4 (3.4)	28 (35.9)	3 (3.8)
cT3	72 (67.9)	115 (96.6)	50 (64.1)	75 (96.2)
Clinical nodal stage
cN0	28 (26.4)	8 (6.7)	19 (24.4)	4 (5.1)
cN1	77 (72.6)	32 (26.9)	58 (74.4)	17 (21.8)
cN2	1 (0.9)	79 (66.4)	1 (1.3)	57 (73.1)
MRF threatened
Yes	1 (0.9)	77 (64.7)	1 (1.3)	51 (65.4)
No	102 (96.2)	39 (32.8)	75 (96.2)	25 (32.0)
Unknown	3 (2.8)	3 (2.5)	2 (2.6)	2 (2.6)
Surgical procedure
LAR	63 (59.4)	61 (51.3)	45 (57.7)	45 (57.7)
Hartmann	10 (9.4)	3 (2.5)	7 (9.0)	2 (2.6)
APR	33 (31.1)	55 (46.2)	26 (33.3)	31 (39.7)
Postoperative stoma
No stoma	22 (20.8)	12 (10.1)	18 (23.1)	10 (12.8)
Temporary	41 (38.7)	50 (42.0)	27 (34.6)	35 (44.9)
Permanent	43 (40.6)	57 (47.9)	33 (42.3)	33 (42.3)
Days to surgery*	4 (3-5)	76 (62–86)	3 (3–5)	76 (62–85)
Months follow-up*	32 (21–49)	39 (25–53)	32 (21–48)	40 (25–51)
Treatment year*	2015 (2014–2016)	2014 (2013–2015)	2015 (2014–2016)	2014 (2013–2015)

Cohort matched on age, sex, comorbidity and tumor location.

*Presented as median (interquartile range).

APR: abdominoperineal resection; CRT-DS: chemoradiation with delayed surgery; LAR: low anterior resection; MRF: mesorectal fascia; SCRT-IS : short-course radiotherapy with immediate surgery.

Table 2. Differences in quality of life domains of the EORTC QLQ-C30 questionnaire between neoadjuvant short-course radiotherapy with immediate surgery (SCRT-IS) and neoadjuvant chemoradiation with delayed surgery (CRT-DS) in a matched cohort of rectal cancer patients.

EORTC QLQ-C30	Group	baseline	3 months			6 months			12 months			18 months			24 months
		Mean (SD)	MD	95% CI	ES^$	MD	95% CI	ES^$	MD	95% CI	ES$	MD	95% CI	ES^$	MD	95% CI	ES^$
Global health	CRT-DS	72.7 (20.9)	−2.2	−8.7 to 4.3	−0.1	−9.1	−15.7 to −2.5	−0.5	−3.2	−10.2 to 3.8	−0.2	−3.5	−11.0 to 3.8	−0.2	3.1	−4.7 to 11.0	0.2
	SCRT-IS	77.3 (16.1)	Ref			Ref			Ref			Ref			Ref
Physical functioning	CRT-DS	88.3 (15.4)	−2.1	−8.2 to 3.9	−0.1	−9.8	−15.9 to −3.6	−0.6	−4.5	−11.0 to 2.0	−0.3	−2.7	−4.0 to 9.4	−0.2	−1.9	−8.9 to 5.1	−0.1
	SCRT-IS	91.4 (15.3)	Ref			Ref			Ref			Ref			Ref
Role functioning	CRT-DS	80.4 (26.0)	−3.2	−13.0 to 6.6	−0.1	−14.0	−24.0 to −4.1	−0.6	−5.5	−16.0 to 5.1	−0.2	−2.0	−13.1 to 9.1	−0.1	0.7	−11.2 to 12.5	0.0
	SCRT-IS	87.7 (22.4)	Ref			Ref			Ref			Ref			Ref
Social functioning	CRT-DS	83.8 (23.7)	−0.9	−9.1 to 7.4	−0.0	−9.2	−17.5 to −0.8	−0.4	−1.0	−9.8 to 7.9	0.0	2.6	−6.5 to 11.8	0.1	0.3	−9.3 to 10.0	0.0
	SCRT-IS	88.9 (18.2)	Ref			Ref			Ref			Ref			Ref
Cognitive functioning	CRT-DS	90.0 (16.9)	−3.2	−9.5 to 3.1	−0.2	−12.6	−19.1 to −6.2	−0.7	−2.7	−9.4 to 4.1	−0.2	−4.9	−11.9 to 2.2	−0.3	−5.7	−13.1 to 1.7	−0.3
	SCRT-IS	88.2 (17.4)	Ref			Ref			Ref			Ref			Ref
Emotional functioning	CRT-DS	78.0 (19.6)	−9.4	−15.7 to −3.1	−0.5	−12.1	−18.5 to −5.8	−0.6	−7.3	−14.0 to −0.6	−0.3	−8.0	−15.1 to −1.0	−0.4	−7.9	−15.5 to −0.3	−0.4
	SCRT-IS	75.7 (22.1)	Ref			Ref			Ref			Ref			Ref

Italic: significant difference between SCRT-IS and CRT-DS based on linear mixed-effects models adjusted for baseline score, surgical procedure and stoma presence.

CI: confidence interval; EORTC: European Organization for Research and Treatment of Cancer; ES: standardized effect size; MD: mean difference; SD: standard deviation. Ref: reference group.

^$Effect size defined as the mean difference divided by the pooled standard deviation of the baseline score and interpreted as ‘no difference’ (ES <0.2), ‘small difference’ (ES =0.2–0.4), ‘moderate difference’ (ES = 0.5–0.7), and ‘large difference’ (ES >0.8).

Figure 2. Within-group changes in quality of life domains of the EORTC QLQ-C30 in a matched cohort of rectal cancer patients receiving short-course radiotherapy with immediate surgery (SCRT-IS) or chemoradiation with delayed surgery (CRT-DS). Scores are presented in mean differences with the 95% confidence intervals (dashed lines). Duration of neoadjuvant treatment and approximate timing of surgery are indicated in the boxes below the graphs and the line respectively.

Figure 3. Categories of symptom severity and sexual interest of the EORTC QLQ-C30 and QLQ-CR29 in the short-course radiotherapy with immediate surgery (SCRT-IS) group and chemoradiation with delayed surgery (CRT-DS) group in a matched cohort of rectal cancer patients. For symptoms, a higher proportion represent more patients with symptoms. For sexual interest, a higher proportion represent more male patients with sexual interest.

Table 3. Results of univariable logistic regression models on the association between treatment strategy and symptoms (moderate/severe versus none/mild) and sexual interest (no versus yes) at 12 and 24 months after the start of treatment in a matched cohort of rectal cancer patients.

Item	Group	12 months			24 months
Moderate/severe:		N (%)	OR	95%CI	N (%)	OR	95%CI
Fatigue	CRT-DS	10/59 (16.9)	1.8	0.6–5.7	9/48 (18.8)	1.1	0.4–3.5
	SCRT-IS	5/49 (10.2)	Ref		6/35 (17.1)	Ref
Insomnia	CRT-DS	10/59 (16.9)	1.5	0.5–4.4	7/48 (14.6)	1.0	0.3–3.5
	SCRT-IS	6/49 (12.2)	Ref		5/35 (14.3)	Ref
Pain	CRT-DS	10/59 (16.9)	1.8	0.6–5.7	7/48 (14.6)	1.3	0.4–4.9
	SCRT-IS	5/49 (10.2)	Ref		4/35 (11.4)	Ref
Stool frequency	CRT-DS	17/57 (29.8)	1.2	0.5–3.0	9/47 (19.1)	1.4	0.4–4.5
	SCRT-IS	12/47 (25.5)	Ref		5/34 (14.7)	Ref
Faecal incontinence	CRT-DS	3/58 (5.2)	0.8	0.2–4.3	4/47 (8.5)	N.A.^#
	SCRT-IS	3/48 (6.3)	Ref		0/35 (0)	Ref
Flatulence	CRT-DS	18/57 (31.6)	2.0	0.8–5.0	11/47 (23.4)	1.2	0.4–3.6
	SCRT-IS	9/48 (18.8)	Ref		7/35 (20.0)	Ref
Urinary frequency	CRT-DS	18/59 (30.5)	1.2	0.5–2.8	15/48 (31.3)	0.9	0.3–2.2
	SCRT-IS	13/49 (26.5)	Ref		12/35 (34.3)	Ref
Urinary incontinence	CRT-DS	10/59 (3.4)	0.5	0.1–3.4	3/48 (6.3)	1.1	0.2–7.0
	SCRT-IS	3/49 (6.1)	Ref		2/35 (5.7)	Ref
Impotence	CRT-DS	12/32 (37.5)	0.7	0.2–1.9	12/21 (57.1)	0.8	0.2–3.1
	SCRT-IS	13/28 (46.4)	Ref		11/18 (61.1)	Ref
No sexual interest in male patients*	CRT-DS	6/32 (18.8)	0.7	0.2–2.6	5/24 (20.8)	0.9	0.2–3.4
	SCRT-IS	6/41 (14.6)	Ref		6/31 (19.4)	Ref

CI: confidence interval; CRT-DS: chemoradiation with delayed surgery; N: number; NA: not applicable; OR: odds ratio; Ref: reference group; SCRT-IS: short-course radiotherapy with immediate surgery.

*Outcomes on sexual interest in female patients are not presented due to insufficient number of responses.

^# No odds ratio was calculated because of zero events in the SCRT-IS group. The difference was non-significant when tested with Fisher’s Exact Test, p = 0.132.