Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

Table 1 Demographic and clinical characteristics of patients

	Group I (n = 45)	Group II (n = 42)	P value
Age (mean ± SD)	53.7 ± 13.4	58 ± 13.2	0.82
Sex (male/female)	32/13	31/11	0.62
Localization of tumor from the anal verge (cm) (mean ± SD)	5.6 ± 3	6.1 ± 2.8	0.39
T stage (2-4)	8/28/9	6/32/4	0.56
Stage (II/III)	4/41	5/37	0.53
Preoperative radiation dose (Gy) (mean)	49.5 ± 1.99	49.5 ± 2	0.78
Follow-up time (mo) (mean ± SD)	37.2 ± 19.6	31.1 ± 20.7	0.51

Table 2 Effect of interval time on the perioperative variables n (%)

	Group I	Group II	P value
	(n = 45)	(n = 42)
Procedure type
LAR	28 (62.2)	31 (73.8)	0.06
ULAR	11 (24.4)	7 (16.7)	0.09
APR	6 (13.3)	4 (9.5)	0.50
Diverting ileostomy	42 (93.3)	39 (92.9)	0.90
Operative time (min) (mean ± SD)	134.2 ± 19.9	133.4 ± 23.5	0.62
Intraoperative complications	8 (8.9)	3 (7.1)	0.48
Postoperative complications	13 (28.9)	11 (26.1)	0.42
Early postoperative mortality	1 (2.3)	2 (4.7)	0.37
Hospital stay (d) (mean ± SD)	11 ± 10.5	10 ± 9.3	0.32

APR: Abdominoperineal resection; LAR: Low anterior resection; ULAR: Ultralow anterior resection.

Table 3 Comparison of pre- and post-treatment stages in both groups n (%)

	Group I (n = 45)		Group II (n = 42)		Comparison of groups I and II
	Pre-treatment	Post-treatment	Pre-treatment	Post-treatment	P value
T stage					0.17
T0	-	9 (18.9)	-	8 (19)
T1	-	2 (4.4)	-	2 (4.8)
T2	8 (17.8)	14 (31.7)	6 (14.3)	14 (33.4)
T3	28 (62.2)	19 (42.8)	32 (76.2)	16 (38.1)
T4	9 (20)	1 (2.2)	4 (9.5)	2 (4.8)
Stage					0.002
Stage 0	-	4 (8.9)	-	8 (19)
Stage 1	-	11 (24.4)	-	15 (35.7)
Stage 2	4 (8.9)	8 (17.8)	2 (11.9)	11 (26.2)
Stage 3	41 (91.1)	22 (48.9)	37 (88.1)	8 (19)
Postop LN without metastasis	21 (46.7)		34 (81)		0.001

Table 4 Analysis of the effect of factors on pathological tumor regression grade

TRG	Relationship between demographics and TRG (p) and OR with 95%CI					Distribution and comparison of TRG rates in both groups
	Age	Sex	Tumor localization	Preop T stage	Preop stage	Group I (n = 45)	Group II (n = 42)	P value
						%	%
Complete response	(0.46)	(0.84)	(0.17)	(0.24)	(0.48)	(n = 4)	(n = 8)	0.36
	2.19, 95%CI: 0.55-8.72	0.54, 95%CI: 0.12-2.29	0.66, 95%CI: 0.15-2.92	1.00, 95%CI: 0.90-1.50	1.21, 95%CI: 0.12-11.8	8.9	19
Near complete response	(0.91)	(0.79)	(0.38)	(0.75)	(0.80)	(n = 9)	(n = 14)	0.35
	1.02, 95%CI: 0.37-2.79	1.11, 95%CI: 0.36-3.38	1.93, 95%CI: 0.64-5.8	0.50, 95%CI: 0.12-2.57	0.36, 95%CI: 0.10-1.51	20	33.3
Minimal response	(0.79)	(0.59)	(0.12)	(0.66)	(0.38)	(n = 12)	(n = 16)	0.15
	0.67, 95%CI: 0.25-1.76	1.25, 95%CI: 0.43-3.63	0.45, 95%CI: 0.16-1.20	2.25, 95%CI: 0.36-13.8	2.02, 95%CI: 0.37-10.9	26.7	38.1
Poor response	(0.48)	(0.95)	(0.11)	(0.19)	(0.70)	(n = 20)	(n = 4)	0.002
	0.98, 95%CI: 0.35-2.76	0.94, 95%CI: 0.31-2.82	1.65, 95%CI: 0.56-4.84	3.22, 95%CI: 0.92-11.2	1.34, 95%CI: 0.23-7.62	44.4	9.5

P < 0.05 is statistical significance. OR: Odds ratio; TRG: Tumor regression grade.

Table 5 Effect of factors on overall survival and disease-free survival

	OS		DFS
	P value	HR with 95%CI	P value	HR with 95%CI
Sex	0.61	0.97, 95%CI: 0.19-4.99	0.69	0.50, 95%CI: 0.46-4.46
Age	0.57	1.01, 95%CI: 0.95-1.08	0.60	1.00, 95%CI: 0.94-1.06
Tumor localization	0.53	0.97, 95%CI: 0.72-1.30	0.88	1.17, 95%CI: 0.80-1.70
Pre-treatment stage	0.94	0.77, 95%CI: 0.80-7.50	0.45	0.90, 95%CI: 0.80-1.50
Pre-treatment T stage	0.59	1.08, 95%CI: 0.21-5.48	0.39	0.39, 95%CI: 0.15-3.02
Post-treatment stage	0.01	18.07, 95%CI: 0.60-53.9	0.007	0.82, 95%CI: 0.10-6.23
Post-treatment T stage	0.13	0.62, 95%CI: 0.34-11.3	0.07	0.25, 95%CI: 0.19-8.54
Postoperative metastatic lymph node (+)	0.001	0.91, 95%CI: 0.69-1.20	0.001	1.25, 95%CI: 0.93-1.67
Pathologic TRG	0.11	0.90, 95%CI: 1.28-6.35	0.04	1.19, 95%CI: 0.17-8.41

DFS: Disease-free survival; OS: Overall survival; TRG: Tumor regression grade.

Table 6 Studies comparing the effects of the interval periods between neoadjuvant therapy and surgery on oncological outcome in locally advanced rectal cancer

Ref.	Total no. of patients	Design	Interval time (wk)	pCR	Local recurrence	OS
Francois et al[6]	201	Prospective, randomized	2/6-8	7%/14%2	13%/10%2	69%/66%2
Wolthuis et al[20]	356	Retrospective	≤ 7/> 7	16%/28%2	6%/3%2	NA
Kalady et al[21]	306	Prospective	< 8/≥ 8	16.3%/28%2	NA	NA
Garcia-Aguilar et al[22]	136	Prospective, nonrandomized	6/11	18%/25%2	NA	NA
de Campos-Lobato et al[23]	177	Retrospective	< 8/≥ 8	16.5%/30.8%2	1.2%/10.5%2	NA
Tulchinsky et al[24]	132	Retrospective	≤ 7/> 7	17%/35%2	6%/4%1	81%/93%2
Sloothaak et al[25]	1593	Prospective	< 13/13-14/15-16	10%/13%/18%1	NA	NA
Saglam et al[31]	153	Prospective, randomized	4/8	19.7%/14.3%2	11.8%/10.3%2	76.5%/74.2%2
Rödel et al[36]	385	Prospective	> 6	10.4%	3%	85%
Kerr et al[42]	189	Retrospective	Median 76 d	15.9%	21%	NA
			(6-215 d)

¹Significant difference statistically;

²Not significant difference statistically. pCR: Pathological complete response; NA: Not available; OS: Overall survival.