Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

Table 1 Clinicopathological characteristics of patients, n (%)

Characteristics	Total cohort (n = 282)	ER (n = 169)	DR (n = 113)	P value
Age (years)	61.87 ± 8.333	61.91 ± 8.051	61.81 ± 8.775	0.928
Gender (male)	154 (54.6)	92 (54.4)	62 (54.9)	0.943
Smoking	40 (14.2)	19 (11.2)	21 (18.6)	0.083
Drinking	23 (8.2)	12 (7.1)	11 (9.7)	0.415
DM	108 (38.3)	65 (38.5)	43 (38.1)	0.945
Jaundice	74 (26.2)	47 (27.8)	27 (23.9)	0.464
Operation types (PD/TP)1	236 (83.7)	147 (87.0)	89 (78.8)	0.067
Tumor sites2	251 (89.0)	152 (89.9)	99 (87.6)	0.540
Tumor size (cm)	3.739 ± 1.482	3.898 ± 1.486	3.501 ± 1.450	0.027
Poor differentiation	142 (50.4)	95 (56.2)	47 (41.6)	0.021
Perineural invasion	224 (79.4)	144 (85.2)	80 (70.8)	0.003
PV invasion	120 (42.6)	82 (48.5)	38 (33.6)	0.013
Lymphnode status (N0)	129 (45.7)	65 (38.5)	64 (56.6)	0.003
Pathological stage (stage III)	109 (38.7)	79 (46.7)	30 (26.5)	0.001
Median RFS (months IQR)	8.37 (3.23-15.92)	4.16 (2.26-7.20)	19.10 (14.60-29.77)	< 0.001

¹Pancreaticoduodenectomy and total pancreatectomy.

²Head and neck of pancreas.

ER: Early recurrence; DR: Delayed recurrence; DM: Diabetes mellitus; PD: Pancreaticoduodenectomy; TP: Total pancreatectomy; RFS: Recurrence free survival.

Table 2 Recurrence sites of patients, n (%)

Site	ER (n = 169)	DR (n = 50)	P value
Liver	70 (41.42)	10 (20.00)	0.009
Lung	2 (1.28)	0 (0)	1
Locoregional recurrence	19 (11.24)	15 (30.00)	0.002
Peritoneal and omental metastasis	7 (4.14)	2 (4.00)	1
Other sites or indeterminate site	71 (42.01)	23 (46.00)	0.735

ER: Early recurrence; DR: Delayed recurrence.

Table 3 Univariate and multivariate Cox regression analyses of the risk factor of early recurrence (with postoperative serum tumor markers)

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Operation types (PD/TP)1	1.445 (0.987-2.115)	0.057
Age (> 63)	1.093 (0.836-1.428)	0.513
Gender (male)	0.920 (0.706-1.200)	0.543
Smoking	0.761 (0.511-1.133)	0.179
Drinking	0.713 (0.421-1.207)	0.209
DM	1.004 (0.765-1.318)	0.974
Jaundice	0.994 (0.736-1.342)	0.971
Tumor_sites2	1.185 (0.769-1.826)	0.440
Tumor_size (> 3.5 cm)	1.431 (1.097-1.866)	0.008
Poor_differentiation	1.380 (1.056-1.804)	0.018
Perineural_invasion	1.970 (1.364-2.845)	< 0.001	2.198 (1.378-3.505)	< 0.001
PV_invasion	1.510 (1.156-1.971)	0.002
Lymphnode_metastasis	1.551 (1.183-2.035)	0.001
pTNM_stage (stage III)	1.728 (1.321-2.259)	< 0.001	1.635 (1.186-2.253)	0.002
Pre_CA19-9 (> 161.50 U/mL)	1.557 (1.189-2.038)	0.001
Pre_CEA (> 4.10 ng/mL)	1.461 (1.096-1.948)	0.009
Pre_CA125 (> 13.80 U/mL)	1.882 (1.431-2.475)	< 0.001	1.812 (1.321-2.487)	< 0.001
Af_CA19-9 (> 34.42 U/mL)	3.297 (2.400-4.528)	< 0.001	2.175 (1.534-3.083)	< 0.001
Af_CEA (> 2.93 ng/mL)	2.227 (1.613-3.074)	< 0.001	1.760 (1.248-2.483)	0.001
Af_CA125 (> 107.00 U/mL)	1.427 (0.974-2.091)	0.067

¹Pancreaticoduodenectomy and total pancreatectomy.

²Head and neck of pancreas.

PD: Pancreaticoduodenectomy; TP: Total pancreatectomy; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 4 Univariate and multivariate Cox regression analyses of the risk factor of early recurrence (without postoperative serum tumor markers)

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Operation types (PD/TP)1	1.445 (0.987-2.115)	0.057
Age (> 63)	1.093 (0.836-1.428)	0.513
Gender (male)	0.920 (0.706-1.200)	0.543
Smoking	0.761 (0.511-1.133)	0.179
Drinking	0.713 (0.421-1.207)	0.209
DM	1.004 (0.765-1.318)	0.974
Jaundice	0.994 (0.736-1.342)	0.971
Tumor_sites2	1.185 (0.769-1.826)	0.440
Tumor_size (> 3.5 cm)	1.431 (1.097-1.866)	0.008
Poor_differentiation	1.380 (1.056-1.804)	0.018
Perineural_invasion	1.970 (1.364-2.845)	< 0.001	2.001 (1.345-2.975)	< 0.001
PV_invasion	1.510 (1.156-1.971)	0.002
Lymphnode_metastasis	1.551 (1.183-2.035)	0.001
pTNM_stage (stage III)	1.728 (1.321-2.259)	< 0.001	1.595 (1.210-2.103)	< 0.001
Pre_CA19-9 (> 161.50 U/mL)	1.557 (1.189-2.038)	0.001	1.350 (1.025-1.779)	0.032
Pre_CEA (> 4.10 ng/mL)	1.461 (1.096-1.948)	0.009
Pre_CA125 (> 13.80 U/mL)	1.882 (1.431-2.475)	< 0.001	1.824 (1.378-2.415)	< 0.001

¹Pancreaticoduodenectomy and total pancreatectomy.

²Head and neck of pancreas.

PD: Pancreaticoduodenectomy; TP: Total pancreatectomy; DM: Diabetes mellitus; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 5 Stratified analysis of clinicopathological variables

Variables	RNS		P value
	High-risk (n = 98)	Low-risk (n = 122)
Operation types (PD/TP)1	90.82	79.51	0.034
Age (> 63)	45.92	38.52	0.333
Gender (male)	62.24	53.28	0.230
Smoking	12.24	18.85	0.251
Drinking	9.18	9.84	1
DM	41.84	33.61	0.265
Jaundice	28.57	27.05	0.921
Tumor_sites2	93.88	86.07	0.096
Tumor_size (> 3.5 cm)	59.18	35.25	< 0.001
Poor_differentiation	62.24	43.44	0.008
Perineural_invasion	95.92	68.85	< 0.001
PV_invasion	52.04	36.89	0.034
Lymphnode_metastasis	58.16	45.90	0.094
pTNM_stage (stage III)	62.24	15.57	< 0.001
Pre_CA19-9 (> 161.50 U/mL)	62.24	31.97	< 0.001
Pre_CEA (> 4.10 ng/mL)	44.90	20.49	< 0.001
Pre_CA125 (> 13.80 U/mL)	77.55	35.25	< 0.001
Af_CA19-9 (> 34.42 U/mL)	62.24	4.92	< 0.001
Af_CEA (> 2.93 ng/mL)	58.16	6.56	< 0.001
Af_CA125 (> 107.00 U/mL)	18.37	15.57	0.711

¹Pancreaticoduodenectomy and total pancreatectomy.

²Head and neck of pancreas.

RNS: Recurrence Nomogram Score; PD: Pancreaticoduodenectomy; TP: Total pancreatectomy; DM: Diabetes mellitus; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.