Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients

Table 1 Patient and tumor characteristics

Variable	Interval ≤ 9 wk (group A, n = 139)	Interval > 9 wk (group B, n = 92)	P value
Sex, n (%)			0.279
Male	100 (71.9)	60 (65.2)
Female	39 (28.1)	32 (34.8)
Age (year, mean ± SD)	58.6 ± 10.6	58.9 ± 11.7	0.645
ASA, n (%)			0.280
1	4 (2.9)	3 (3.3)
2	111 (79.9)	67 (72.8)
3	24 (17.2)	22 (23.9)
BMI (kg/m2 , mean ± SD)	23.8 ± 3.4	24.4 ± 2.9	0.063
cT, n (%)			0.318
2	2 (1.4)	0 (0)
3	110 (79.1)	70 (76)
4	27 (19.4)	22 (24)
cN, n (%)			0.355
0	40 (28.8)	22 (23.9)
1	71 (51.1)	48 (52.2)
2	28 (20.1)	22 (23.9)
Preoperative carcinoembryonic antigen (μg/L, mean ± SD)	5.4 ± 10.8	5.8 ± 13.7	0.182
Preoperative concurrent chemotherapy regimen, n (%)			0.712
Capecitabine + oxaliplatin	32 (23)	29 (31.5)
Capecitabine oral	87 (62.6)	58 (63)
Oxaliplatin union	21 (15.1)	5 (5.4)

BMI: Body mass index; ASA: American Society of Anesthesiologists.

Table 2 Surgical results and tumor outcomes

Variable	Interval ≤ 9 wk	Interval > 9 wk	P value
	(group A, n = 139)	(group B, n = 92)
Surgical procedure
Miles (n, %)	55 (39.6)	45 (48.9)	0.161
Dixon (n, %)	73 (52.5)	40 (43.5)	0.179
Hartmann (n, %)	11 (7.9)	7 (7.6)	0.933
Operative time (min, mean ± SD)	194.5 ± 65.2	222.2 ± 67.8	0.001
Estimated blood loss (mL, mean ± SD)	68.0 ± 92.1	100.9 ± 133.9	0.007
Postoperative complications	7 (5)	5 (5.4)	0.894
Hemorrhage, n (%)	1 (0.7)	1 (1.1)
Anastomotic leakage, n (%)	5 (3.6)	2 (2.2)
Ileus, n (%)	2 (1.4)	0 (0)
Reoperation, n (%)	3 (2.2)	1 (1.1)
Cardiovascular, n (%)	0 (0)	1 (1.1)
Urinary retention, n (%)	1 (0.7)	2 (2.2)
Exhaust, d (mean ± SD)	3.6 ± 1.5	3.9 ± 1.5	0.148
Defecation, d (mean ± SD)	4.7 ± 1.7	5.2 ± 2.0	0.249
Micturition, d (mean ± SD)	4.5 ± 1.4	4.4 ± 1.0	0.614
Degree of differentiation, n (%)			0.475
Low and low-moderate grades	22 (15.8)	10 (10.9)
Moderate, moderate-high, and high grades	114 (82)	79 (85.9)
Signet-ring and mucinous adenocarcinoma	3 (2.2)	3 (3.3)
ypT, n (%)			0.009
1	3 (2.2)	2 (2.2)
2	29 (20.9)	19 (20.7)
3	82 (59)	39 (42.4)
4	10 (7.2)	7 (7.6)
ypN, n (%)			0.014
0	68 (48.9)	60 (65.2)
1	50 (36)	24 (26.1)
2	21 (15.1)	8 (8.7)
pCR	15 (10.8)	25 (27.2)	0.001
Total lymph nodes	19.0 ± 8.8	15.7 ± 8.7	0.001
Positive lymph nodes	1.6 ± 3.2	0.8 ± 1.7	0.045

pCR: Pathologic complete response.

Table 3 Multivariate logistic regression analysis identifying independent factors affected by interval time

Variable	P value	OR	95%CI
ypT
ypT1 vs ypT4	0.799	0.753	0.085-6.655
ypT2 vs ypT4	0.779	0.841	0.25-2.826
ypT3 vs ypT4	0.538	0.705	0.233-2.14
ypN
ypN0 vs ypN2	0.511	0.492	0.059-4.082
ypN1 vs ypN2	0.431	0.469	0.071-3.082
Positive lymph nodes	0.234	0.922	0.807-1.054
Total lymph nodes	0.007	0.952	0.918-0.986
pCR	0.009	2.668	1.276-5.578
Operative time	0.010	1.006	1.001-1.01
Estimated blood loss	0.093	1.002	1-1.005

pCR: Pathologic complete response; OR: Odds ratio.

Table 4 Pathologic response

Variable	Interval ≤ 9 wk	Interval > 9 wk	P value
	(group A, n = 139)	(group B, n = 92)
No downstaging, TNM (n, %)	83 (59.7)	35 (38)	0.001
Downstaging, TNM (n, %)	41 (29.5)	32 (34.8)	0.129
T, n (%)			0.016
No downstaging	83 (59.7)	52 (56.5)
Downstaging	56 (40.3)	40 (43.5)
N, n (%)			0.010
No downstaging	100 (71.9)	51 (55.4)
Downstaging	39 (28.1)	41 (44.6)

TNM: Tumor node metastasis.

Table 5 Patterns of disease recurrence according to study group

Variable	Interval ≤ 9 wk	Interval > 9 wk	P value
	(group A, n = 139)	(group B, n = 92)
Local recurrence, n (%)	12 (8.6)	8 (8.7)	0.987
Distant recurrence, n (%)	40 (28.8)	10 (10.9)	0.001
Death	26 (18.7)	12 (13)	0.661

Table 6 Kaplan-Meier survival estimates

Variable	No. of cases	DFS P value	OS P value
Sex (n, %)		0.668	0.448
Male	160 (69.3)
Female	71 (30.7)
Age (year)		0.518	0.688
< 60	111 (48.1)
≥ 60	120 (51.9)
ASA (n, %)		0.691	0.658
1	7 (3)
2	178 (77)
3	46 (19.9)
BMI (kg/m2)		0.759	0.587
< 25	149 (64.5)
≥ 25	82 (35.5)
Interval time, w (%)		0.002	0.259
≤ 9 wk	139 (60.2)
> 9 wk	92 (39.8)
cT, n (%)		0.343	0.483
2	2 (0.9)
3	180 (77.9)
4	49 (21.2)
cN, n (%)		0.059	0.084
0	62 (26.8)
1	119 (51.5)
2	50 (21.6)
ypT, n (%)		< 0.001	0.001
0	40 (17.3)
1	5 (2.2)
2	48 (20.8)
3	121 (52.4)
4	17 (7.4)
ypN, n (%)		0.001	0.185
0	128 (55.4)
1	74 (32)
2	29 (12.6)
Surgical procedure		0.109	0.464
Miles (n, %)	100 (43.3)
Dixon (n, %)	113 (48.9)
Hartmann (n, %)	18 (7.8)
Postoperative complications, n (%)		0.265	0.043
Yes	12 (5.2)
No	219 (94.8)
Degree of differentiation, n (%)		0.094	0.183
Low and low-moderate grades	32 (13.9)
Moderate, moderate-high, and high grades	193 (83.5)
Signet-ring and mucinous adenocarcinoma	6 (2.6)
Preoperative concurrent chemotherapy regimen, n (%)		0.357	0.533
Capecitabine + oxaliplatin	71 (30.7)
Capecitabine oral	145 (62.8)
Oxaliplatin union	15 (6.5)

BMI: Body mass index; ASA: American Society of Anesthesiologists; DFS: Disease-free survival; OS: Overall survival.

Table 7 Cox regression analysis

Variable	Disease-free survival			Overall survival
	OR	95%CI	P value	OR	95%CI	P value
Interval time
> 9 wk vs ≤ 9 wk	0.570	0.328-0.991	0.046	0.825	0.411-1.656	0.589
Postoperative complications	1.322	0.527-3.368	0.544	2.187	0.764-6.255	0.145
ypT
ypT0 vs ypT4	0.047	0.01-0.214	< 0.01	0.065	0.014-0.307	0.001
ypT1 vs ypT4	0.173	0.022-1.337	0.093	0.253	0.031-2.031	0.196
ypT2 vs ypT4	0.102	0.038-0.275	< 0.01	0.076	0.02-0.288	0.001
ypT3 vs ypT4	0.387	0.205-0.731	0.003	0.287	0.128-0.641	0.002
ypN
ypN0 vs ypN2	0.705	0.35-1.421	0.329	0.765	0.282-2.077	0.599
ypN1 vs ypN2	0.967	0.504-1.853	0.919	0.939	0.363-2.426	0.897

OR: Odds ratio.