Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms

Table 1 Characteristics of patients, n (%)

Variables	Total, n = 895	Training set, n = 627	Testing set, n = 268	Statistics	P value
Gender				χ2 = 0.197	0.657
Female	471 (52.63)	333 (53.11)	138 (51.49)
Male	424 (47.37)	294 (46.89)	130 (48.51)
Age, yr, mean ± SD	63.79 ± 13.05	63.62 ± 12.89	64.18 ± 13.44	t = 0.58	0.560
Race				χ2 = 4.244	0.120
Black	140 (15.64)	93 (14.83)	47 (17.54)
White	670 (74.86)	481 (76.71)	189 (70.52)
Others1	85 (9.50)	53 (8.45)	32 (11.94)
Marital status				χ2 = 6.700	0.082
Divorce	93 (10.39)	74 (11.80)	19 (7.09)
Married	484 (54.08)	326 (51.99)	158 (58.96)
Single	152 (16.98)	105 (16.75)	47 (17.54)
Others2	166 (18.55)	122 (19.46)	44 (16.42)
Primary tumor site				χ2 = 0.478	0.924
Left	623 (69.61)	437 (69.70)	186 (69.40)
Rectum	154 (17.21)	109 (17.38)	45 (16.79)
Right	99 (11.06)	69 (11.00)	30 (11.19)
Overlapping lesion of colon/colon/unknown	19 (2.12)	12 (1.91)	7 (2.61)
G staging				χ2 = 1.664	0.797
I	268 (29.94)	185 (29.51)	83 (30.97)
II	124 (13.85)	90 (14.35)	34 (12.69)
III	279 (31.17)	190 (30.30)	89 (33.21)
IV	119 (13.30)	85 (13.56)	34 (12.69)
Unknown	105 (11.73)	77 (12.28)	28 (10.45)
T staging				-	0.155
T1	112 (12.51)	82 (13.08)	30 (11.19)
T2	85 (9.50)	67 (10.69)	18 (6.72)
T3	471 (52.63)	321 (51.20)	150 (55.97)
T4	224 (25.03)	156 (24.88)	68 (25.37)
TX	3 (0.34)	1 (0.16)	2 (0.75)
N staging				χ2 = 0.107	0.948
N0	223 (24.92)	158 (25.20)	65 (24.25)
N1	479 (53.52)	335 (53.43)	144 (53.73)
N2	193 (21.56)	134 (21.37)	59 (22.01)
M staging				χ2 = 0.147	0.701
M0	613 (68.49)	427 (68.10)	186 (69.40)
M1	282 (31.51)	200 (31.90)	82 (30.60)
Tumor size				χ2 = 0.796	0.372
< 5 cm	619 (69.16)	428 (68.26)	191 (71.27)
≥ 5 cm	276 (30.84)	199 (31.74)	77 (28.73)
Perineural invasion				χ2 = 0.986	0.611
No	57 (6.37)	41 (6.54)	16 (5.97)
Yes	29 (3.24)	18 (2.87)	11 (4.10)
Unknown	809 (90.39)	568 (90.59)	241 (89.93)
Number of PLN, M (Q1, Q3)	3.00 (0.00, 7.00)	3.00 (0.00, 7.00)	3.00 (1.00, 7.00)	Z = -0.443	0.658
Number of total lymph nodes, M (Q1, Q3)	15.00 (11.00, 22.00)	15.00 (11.00, 21.00)	16.00 (11.00, 22.50)	Z = 0.395	0.693
LNR, M (Q1, Q3)	0.21 (0.00, 0.50)	0.21 (0.00, 0.50)	0.21 (0.03, 0.50)	Z = -0.312	0.755
LODDS, M (Q1, Q3)	0.30 (0.07, 1.00)	0.31 (0.08, 1.00)	0.30 (0.07, 1.00)	Z = -0.492	0.623
CEA				χ2 = 3.341	0.188
Negative	37 (4.13)	21 (3.35)	16 (5.97)
Positive	19 (2.12)	14 (2.23)	5 (1.87)
Unknown	839 (93.74)	592 (94.42)	247 (92.16)
Chemotherapy				χ2 = 0.000	0.992
No/unknown	651 (72.74)	456 (72.73)	195 (72.76)
Yes	244 (27.26)	171 (27.27)	73 (27.24)
Radiation				χ2 = 0.077	0.781
No/unknown	851 (95.08)	597 (95.22)	254 (94.78)
Yes	44 (4.92)	30 (4.78)	14 (5.22)
Follow-up time, M (Q1, Q3)	42.00 (9.00, 73.00)	42.00 (9.00, 73.00)	42.00 (7.50, 75.50)	Z = -0.000	1.000
Vital status				χ2 = 0.197	0.657
Survival	404 (45.14)	280 (44.66)	124 (46.27)
Dead	491 (54.86)	347 (55.34)	144 (53.73)

¹Others, American Indian/AK Native, Asian/Pacific Islander, and Unknown.

²Others, Separated, Unknown, Unmarried or Domestic Partner, and Widowed.

G: Grade; T: Tumor; N: Node; M: Metastasis; PLN: Positive lymph node; LNR: Lymph node ratio; LODDS: Log odds of positive lymph nodes; CEA: Carcinoembryonic antigen.

Table 2 The association of positive lymph node, lymph node ratio, and log odds of positive lymph nodes on the prognosis of colorectal neuroendocrine neoplasms treated surgically

Variables	Model 11	P value	Model 22	P value	Model 33	P value
	HR (95%CI)		HR (95%CI)		HR (95%CI)
PLN staging
Tile 1 (< 5)	Ref		Ref		Ref
Tile 2 (5-10)	1.10 (0.83-1.45)	0.526	1.28 (0.96-1.70)	0.090	1.14 (0.84-1.56)	0.400
Tile 3 (≥ 10)	3.67 (2.85-4.73)	< 0.001	3.56 (2.76-4.59)	< 0.001	2.05 (1.54-2.74)	< 0.001
LNR staging
Tile 1 (< 0.30)	Ref		Ref		Ref
Tile 2 (0.30-0.65)	1.43 (1.10-1.87)	0.008	1.67 (1.28-2.19)	< 0.001	1.54 (1.15-2.07)	0.004
Tile 3 (≥ 0.65)	4.49 (3.48-5.81)	< 0.001	4.48 (3.46-5.79)	< 0.001	2.98 (2.21-4.01)	< 0.001
LODDS staging
Tile 1 (< 0.47)	Ref		Ref		Ref
Tile 2 (0.47-1.59)	1.34 (1.02-1.76)	0.039	1.56 (1.18-2.06)	0.002	1.47 (1.09-1.99)	0.013
Tile 3 (≥ 1.59)	4.42 (3.44-5.68)	< 0.001	4.36 (3.38-5.61)	< 0.001	3.03 (2.26-4.05)	< 0.001

¹Model 1: Coarse model.

²Model 2: Adjusted gender and age.

³Model 3: Adjusted gender, age, marital status, primary tumor site, grade stage, tumor stage, metastasis stage, tumor size, perineural invasion, carcinoembryonic antigen, and chemotherapy.

PLN: Positive lymph node; LNR: Lymph node ratio; LODDS: Log odds of positive lymph nodes; HR: Hazard ratio; CI: Confidence interval.

Table 3 The prediction of positive lymph node, lymph node ratio, and log odds of positive lymph nodes on the prognosis of neuroendocrine neoplasms

Variables	Training set	Testing set
	C-index (95%CI)	C-index (95%CI)
PLN staging	0.620 (0.593-0.648)	0.648 (0.608-0.689)
LNR staging	0.645 (0.618-0.672)	0.670 (0.630-0.710)
LODDS staging	0.643 (0.615-0.670)	0.675 (0.634-0.715)

PLN: Positive lymph node; LNR: Lymph node ratio; LODDS: Log odds of positive lymph nodes; CI: Confidence interval; C-index: Concordance index.

Table 4 Subgroup analysis according to the grade staging

G stage	C-index (95%CI)
I + II
PLN staging	0.545 (0.464-0.627)
LNR staging	0.633 (0.540-0.726)
LODDS staging	0.638 (0.545-0.730)
III + IV
PLN staging	0.616 (0.564-0.668)
LNR staging	0.637 (0.585-0.688)
LODDS staging	0.638 (0.587-0.689)

G: Grade; PLN: Positive lymph node; LNR: Lymph node ratio; LODDS: Log odds of positive lymph nodes; CI: Confidence interval; C-index: Concordance index.