Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy

Table 1 Patient characteristics

Variable	TLN ≥ 12 (group A, n = 177)	TLN < 12 (group B, n = 54)	P value
Sex (n, %)			0.591
Male	121 (68.4)	39 (72.2)
Female	56 (31.6)	15 (27.8)
Age (yr)	60 (51-65)	59.5 (52.75-66.5)	0.544
ASA score (n, %)			0.488
1	5 (2.8)	2 (3.7)
2	139 (78.6)	39 (72.2)
3	33 (18.6)	13 (24.1)
BMI (kg/m2)	23.8 (21.9-26.4)	23.4 (21.5-25.2)	0.423
cT, n (%)			0.975
2	2 (1.1)	0 (0)
3	137 (77.4)	43 (79.6)
4	38 (21.5)	11 (20.4)
cN, n (%)			0.109
0	44 (24.9)	18 (33.3)
1	91 (51.4)	28 (51.9)
2	42 (23.7)	8 (14.8)
Preoperative CEA (μg/L)	2.99 (1.55-5.57)	3 (1.68-5.57)	0.729
ypT, n (%)			0.140
0	26 (14.7)	14 (25.9)
1	4 (2.3)	1 (1.9)
2	37 (20.9)	11 (20.4)
3	97 (54.8)	24 (44.4)
4	13 (7.3)	4 (7.4)
ypN, n (%)			0.026
0	90 (50.8)	38 (70.4)
1	64 (36.2)	10 (18.5)
2	23 (13)	6 (11.1)
TRG, n (%)			0.312
0	14 (7.9)	4 (7.4)
1	26 (14.7)	7 (13)
2	78 (44.1)	22 (40.7)
3	33 (18.6)	7 (13)
4	26 (14.7)	14 (25.9)
No downstaging, n (%)	98 (55.4)	20 (37)	0.019
Downstaging, n (%)	56 (31.6)	21 (38.9)	0.324
pCR, n (%)	26 (14.7)	14 (25.9)	0.057
Positive lymph nodes, n (%)	0 (0-1)	0 (0-0)	0.003
LNR	0 (0-0.68)	0 (0-0)	0.012
Radiotherapy dose, n (%)			0.557
45-50.4 Gy/28 F	125 (70.6)	39 (72.2)
< 45 Gy/25 F	34 (19.2)	5 (9.3)
25 Gy/5 F	18 (10.2)	10 (18.5)
Preoperative concurrent chemotherapy regimen, n (%)			0.376
Capecitabine+ oxaliplatin	54 (30.5)	17 (31.5)
Capecitabine, oral	108 (61)	37 (68.5)
Fluorouracil union	15 (8.5)	0 (0)
Tumor location, DAV (cm)	5 (3-7)	5 (3-7)	0.605
Interval, w (%)	8 (6.5-11)	10 (8-16)	0.001
Surgical procedure			0.018
Miles (n, %)	74 (41.8)	26 (48.2)
Dixon (n, %)	93 (52.5)	20 (37)
Hartmann (n, %)	10 (5.6)	8 (14.8)
LLND (n, %)	20 (11.3)	1 (1.9)	0.035
Multivisceral resection (n, %)	10 (5.6)	2 (3.7)	0.574
PNI (n, %)			0.819
Yes	42 (23.7)	12 (22.2)
No	135 (76.3)	42 (77.8)
Intravascular tumor embolus (n, %)			0.463
Yes	23 (13)	5 (9.3)
No	154 (87)	49 (90.7)
Degree of differentiation, n (%)			0.367
Low and low-middle grades	18 (10.2)	9 (16.7)
Middle, high-middle, and high grades	132 (74.6)	43 (79.6)
Signet-ring and mucinous adenocarcinoma	4 (2.3)	2 (3.7)

TLN: Total number of retrieved lymph nodes; BMI: Body mass index; CEA: Carcinoembryonic antigen; ASA: American Society of Anesthesiologists; TRG: Tumor regression grade; LNR: Lymph node ratio; DAV: Distance from anal verge; LLND: Lateral lymph node dissection; PNI: Perineural invasion; pCR: Pathological complete response; F: Fractions.

Table 2 Binary regression analysis

	P value	OR	95%CI
No downstaging	0.640	0.797	0.309-2.061
Positive lymph nodes	0.152	0.873	0.725-1.051
ypN0 vs ypN2	0.059	8.239	0.92-73.794
ypN1 vs ypN2	0.442	2.228	0.289-17.163
LNR	0.039	66.666	1.239-3587.217
Interval	0.002	1.084	1.029-1.142
LLND	0.086	0.165	0.021-1.287

LNR: Lymph node ratio; LLND: Lateral lymph node dissection; OR: Odds ratio; CI: Confidence interval.

Table 3 Oncologic outcomes

Variable	TLN ≥ 12 (group A, n = 177)	TLN < 12 (group B, n = 54)	P value
Local recurrence, n (%)	14 (7.9)	7 (13)	0.259
Distant recurrence, n (%)	35 (19.8)	20 (37)	0.009
Death, n (%)	27 (15.3)	9 (16.7)	0.803

TLN: Total number of retrieved lymph nodes.

Table 4 Results of Kaplan-Meier analysis

Variable	No. of cases	DFS P value	OS P value
Sex (n, %)		0.708	0.655
Male	160 (69.3)
Female	71 (30.7)
Age (yr)		0.86	0.968
< 60	111 (48.1)
≥ 60	120 (51.9)
ASA score (n, %)		0.912	0.951
1	7 (3)
2	178 (77)
3	46 (19.9)
BMI (kg/m2)		0.519	0.512
< 25	149 (64.5)
≥ 25	82 (35.5)
cT, n (%)		0.606	0.476
2	2 (0.9)
3	180 (77.9)
4	49 (21.2)
cN, n (%)		0.003	0.063
0	79 (34.2)
1	112 (48.5)
2	40 (17.3)
ypT, n (%)		< 0.001	< 0.001
0	36 (15.6)
1	6 (2.6)
2	50 (21.6)
3	122 (52.8)
4	17 (7.4)
ypN, n (%)		< 0.001	0.097
0	128 (55.4)
1	74 (32)
2	29 (12.6)
TLN, n (%)		0.006	0.737
< 12	54 (23.4)
≥ 12	177 (76.6)
Positive lymph nodes, n (%)		< 0.001	0.063
< 2	182 (78.8)
≥ 2	49 (21.2)
LNR		< 0.001	0.058
≤ 0.03
> 0.03
Preoperative concurrent chemotherapy regimen, n (%)		0.148	0.561
Capecitabine+ oxaliplatin	58 (25.1)
Capecitabine, oral	140 (60.6)
Oxaliplatin combination	22 (9.5)
Postoperative chemotherapy		0.933	0.869
Yes	153 (66.2)
No	78 (33.8)
Interval, w (%)		0.044	0.567
≤ 8 wk	139 (60.2)
> 8 wk	92 (39.8)
Surgical procedure		0.168	0.662
Miles (n, %)	100 (43.3)
Dixon (n, %)	113 (48.9)
Hartmann (n, %)	18 (7.8)
LLND (n, %)	21 (9.1)	0.868	0.994
Multivisceral resection (n, %)	12 (5.2)	0.025	0.948
Preoperative CEA (μg/L)		0.344	0.663
< 5	166 (71.9)
≥ 5	65 (28.1)
PNI (n, %)		< 0.001	< 0.001
Yes	54 (23.4)
No	177 (76.6)
Intravascular tumor embolus (n, %)		< 0.001	0.004
Yes	28 (12.1)
No	203 (87.9)
Degree of differentiation, n (%)		0.028	0.152
Low and low-middle grades	32 (13.9)
Middle, high-middle, and high grades	193 (83.5)
Signet-ring and mucinous adenocarcinoma	6 (2.6)

DFS: Disease-free survival; OS: Overall survival; BMI: Body mass index; ASA: American Society of Anesthesiologists; LLND: Lateral lymph node dissection; TLN: Total number of retrieved lymph nodes; CEA: Carcinoembryonic antigen; PNI: Perineural invasion.

Table 5 Results of Cox regression analysis of disease-free survival and overall survival

		Disease-free survival			Overall survival
	P value	HR	95%CI	P value	HR	95%CI
cN0 vs cN1	0.620	0.794	0.318-1.978	0.801	0.84	0.217-3.249
cN0 vs cN2	0.496	1.281	0.628-2.610	0.296	1.712	0.625-4.693
ypT0 vs ypT4	< 0.001	0.074	0.019-0.288	0.011	0.11	0.02-0.607
ypT1 vs ypT4	0.338	0.46	0.094-2.253	0.494	0.464	0.051-4.202
ypT2 vs ypT4	< 0.001	0.097	0.032-0.301	0.002	0.035	0.004-0.305
ypT3 vs ypT4	0.014	0.418	0.209-0.837	0.011	0.309	0.125-0.761
ypN0 vs ypN1	0.745	0.823	0.254-2.664	0.805	1.245	0.219-7.086
ypN0 vs ypN2	0.706	1.178	0.504-2.756	0.816	1.156	0.341-3.92
TLN (≥ 12 vs < 12	< 0.001	0.302	0.172-0.531	0.606	0.8	0.342-1.871
LNR (≤ 0.03 vs 0.03)	0.840	0.914	0.379-2.20	0.768	1.228	0.314-4.799
Positive lymph nodes (≥ 2 vs < 2)	0.828	1.1	0.466-2.593	0.978	0.982	0.271-3.562
Interval (≤ 8 wk vs > 8 wk)	0.236	1.369	0.814-2.303	0.626	0.836	0.408-1.715
Multivisceral resection	0.119	1.875	0.851-4.13	0.792	0.816	0.181-3.69
PNI	0.051	1.8	0.998-3.248	0.002	3.747	1.634-8.592
Intravascular tumor embolus	0.244	1.479	0.766-2.858	0.584	1.292	0.517-3.23
Degree of differentiation
Low and low-middle grades vs signet-ring and mucinous adenocarcinoma	0.695	0.739	0.163-3.354	0.811	0.76	0.08-7.221
Middle, high-middle, and high grades vs signet-ring and mucinous adenocarcinoma	0.929	0.930	0.19-4.564	0.913	1.141	0.106-12.243

TLN: Total number of retrieved lymph nodes; LNR: Lymph node ratio; DFS: Disease-free survival; OS: Overall survival; PNI: Perineural invasion; HR: Hazard ratio; CI: Confidence interval.