Direct gastric invasion is associated with poor prognosis in esophageal squamous cell carcinoma involving the lower-third esophagus

Table 1 Demographic and clinical characteristics of 23 patients with esophageal squamous cell carcinoma and direct gastric invasion

Variable	n (%)
Age in years (mean ± SD)	58.7 ± 9.3
Sex
Male	22 (95.7)
Female	1 (4.3)
Smoking	20 (87.0)
Alcohol consumption	22 (95.7)
Betel nut chewing	14 (60.9)
T category
T2	1 (4.3)
T3	15 (65.2)
T4a	2 (8.7)
T4b	5 (21.7)
N category
N0	1 (4.3)
N1	8 (34.8)
N2	4 (17.4)
N3	10 (43.5)
M category
M0	17 (73.9)
M1	6 (26.1)
Clinical stage
II	2 (8.7)
III	10 (43.5)
IV	11 (47.8)
Histological differentiation
Grade 2, moderately differentiated	15 (65.2)
Grade 3, poorly differentiated	8 (34.8)
Tumor location
Upper to lower third of the esophagus	1 (4.3)
Middle to lower third of the esophagus	4 (17.4)
Lower third of the esophagus	18 (78.3)
Tumor length in cm (median, IQR)	9.0 (7.0-11.7)
Serum albumin in g/dL (mean ± SD)	3.9 ± 0.5
ECOG performance status
0	2 (8.7)
1	17 (73.9)
2	4 (17.4)
Treatment
CRT	15 (65.2)
CRT followed by surgery	5 (21.7)
Best supportive care	3 (13.0)

CRT: Chemoradiotherapy; ECOG: Eastern Cooperative Oncology Group; IQR: Interquartile range; IQR: Interquartile range.

Table 2 Cox proportional hazards regression analysis of overall survival in 23 patients with esophageal squamous cell carcinoma and direct gastric invasion

	Univariable		Multivariable1		Multivariable2
Variable	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age in years
< 58.1	1		1		1
≥ 58.1	1.13 (0.4-2.9)	0.76	1.3 (0.4-4.4)	0.68	0.65 (0.2-2.2)	0.48
Sex
Female	1		1		1
Male	0.68 (0.1-5.4)	0.71	0.1 (0.00-1.8)	0.12	0.2 (0.01-3.7)	0.26
Clinical stage
II	1		1		-
III	1.4 (0.2-11.1)	0.78	2.2 (0.2-24.6)	0.53	-
IV	1.4 (0.2-11.2)	0.77	1.4 (0.2-12.4)	0.78	-
ECOG performance status
0-1	1		1		1
2	18.8 (3.3-107.4)	< 0.01	16.6 (2.7-103.4)	< 0.01	27.2 (3.1-237.2)	< 0.01
T category
T2	1		-		1
T3-T4	1.2 (0.1-8.9)	0.89	-		0.9 (0.1-12.6)	0.94
N category
N0-N1	1		-		1
N2-N3	0.4 (0.1-1.2)	0.11	-		0.5 (0.1-2.2)	0.39
M category
M0	1		-		1
M1	2.1 (0.8-5.8)	0.16	-		2.9 (0.6-13.5)	0.17
Treatment modality
Best supportive care	1		1		1
CRT	0.3 (0.1-1.7)	0.18	0.3 (0.04-1.6)	0.15	0.11 (0.01-1.05)	0.06
CRT followed by surgery	0.1 (0.02-0.7)	0.02	0.03 (0.00-0.5)	0.02	0.03 (0.002-0.6)	0.02

¹Multivariable model adjusted for age, sex, clinical stage, Eastern Cooperative Oncology Group performance status, and treatment modality.

²Multivariable model adjusted for age, sex, clinical T category, clinical N category, clinical M category, Eastern Cooperative Oncology Group performance status, and treatment modality.

ECOG: Eastern Cooperative Oncology Group; CI: Confidence interval; CRT: Chemoradiotherapy; HR: Hazard ratio.

Table 3 Demographic and clinical characteristics of 176 patients with esophageal squamous cell carcinoma involving the lower third of the esophagus, n (%)

Variable	With gastric invasion (n = 20)	Without gastric invasion (n = 156)	P value
Age in years (mean ± SD)	58.2 ± 8.7	57.3 ± 8.3	0.65
< 57.3	10 (50.0)	75 (48.1)	0.87
≥ 57.2	10 (50.0)	81 (51.9)
Sex			0.58
Male	19 (95.0)	150 (96.2)
Female	1 (5.0)	6 (3.8)
T category			0.31
T2	1 (5.0)	23 (14.7)
T3	13 (65)	94 (60.3)
T4a	2 (10.0)	5 (3.2)
T4b	4 (20.0)	34 (21.8)
N category
N0	1 (5.0)	16 (10.3)	0.11
N1	8 (40.0)	50 (32.1)
N2	4 (20.0)	64 (41.0)
N3	7 (35.0)	26 (16.7)
M category
M0	15 (75.0)	137 (87.8)	0.16
M1	5 (25.0)	19 (12.2)
Clinical stage			0.27
I	0 (0.0)	1 (0.6)
II	2 (10.0)	16 (10.3)
III	9 (45.0)	99 (63.5)
IV	9 (45.0)	40 (25.6)
Histological grade			0.41
Grade 1, well differentiated	0 (0.0)	9 (5.8)
Grade 2, moderately differentiated	14 (70.0)	105 (67.3)
Grade 3, poorly differentiated	6 (30.0)	31 (19.9)
Missing	0 (0.0)	11 (7.1)
Tumor location			0.001
Upper to lower third of the esophagus	0 (0.0)	18 (11.5)
Middle to lower third of the esophagus	3 (15.0)	74 (47.4)
Lower third of the esophagus	17 (85.0)	64 (41.0)
Tumor length, cm (median, IQR)	7.1 (6.3-10.8)	7.1 (5.0-10.0)	0.41
Baseline renal function			> 0.99
eGFR < 60 mL/minutes	3 (15.0)	28 (17.9)
eGFR ≥ 60 mL/minutes	17 (85.0)	128 (82.1)
Serum albumin, g/dL (mean ± SD)	3.9 ± 0.5	4.0 ± 0.5	0.69
ECOG performance status			0.08
0	2 (10.0)	24 (15.4)
1	15 (75.0)	127 (81.4)
2	3 (15.0)	5 (3.2)
Treatment modality			0.24
CRT	15 (75.0)	96 (61.5)
CRT followed by surgery	5 (25.0)	60 (38.5)

CRT: Chemoradiotherapy; ECOG: Eastern Cooperative Oncology Group; eGFR: Estimated glomerular filtration rate; IQR: Interquartile range.

Table 4 Cox proportional hazards regression analysis of overall survival in 176 patients with esophageal squamous cell carcinoma involving the lower third of the esophagus, n (%)

	Univariable		Multivariable1		Multivariable2
Variable	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Gastric invasion
No	1		1		1
Yes	2.5 (1.4-4.4)	0.001	2.2 (1.2-3.9)	0.01	1.9 (1.0-3.7)	0.04
Age in years
< 57.3	1		1		1
≥ 57.3	1.1 (0.8-1.6)	0.53	0.8 (0.5-1.2)	0.25	0.8 (0.5-1.2)	0.21
Sex
Female	1		1		1
Male	1.1 (0.4-2.9)	0.92	0.6 (0.2-1.6)	0.32	0.7 (0.2-1.8)	0.41
Clinical stage
I-II	1		1		-
III	1.1 (0.5-2.2)	0.82	1.2 (0.6-2.5)	0.58	-
IV	2.2 (1.1-4.7)	0.03	1.7 (0.8-3.7)	0.15	-
Treatment
CRT	1		1		1
CRT followed by surgery	0.3 (0.2-0.5)	< 0.001	0.3 (0.2-0.5)	0.01	0.3 (0.2-0.5)	< 0.001
ECOG performance status
0	1		1		1
1	1.0 (0.6-1.9)	0.89	1.0 (0.5-2.0)	0.95	0.9 (0.4-1.8)	0.71
2	2.3 (0.9-6.2)	0.09	1.8 (0.6-5.1)	0.27	1.6 (0.5-4.6)	0.43
T category
T2	1		-		1
T3	0.8 (0.5-1.5)	0.60	-		1.2 (0.6-2.6)	0.62
T4	1.7 (0.9-3.2)	0.08	-		1.5 (0.7-3.0)	0.27
N category
N0	1		-		1
N1	1.4 (0.7-2.8)	0.35	-		1.3 (0.6-2.8)	0.55
N2	1.1 (0.5-2.3)	0.77	-		1.0 (0.4-2.1)	0.95
N3	1.4 (0.6-3.1)	0.41	-		1.0 (0.4-2.3)	> 0.99
M category
M0	1		-		1
M1	3.0 (1.8-4.9)	< 0.001	-		1.7 (0.9-2.9)	0.06

¹Multivariable model adjusted for age, sex, clinical stage, Eastern Cooperative Oncology Group performance status, and treatment modality.

²Multivariable model adjusted for age, sex, clinical T category, clinical N category, clinical M category, Eastern Cooperative Oncology Group performance status, and treatment modality.

ECOG: Eastern Cooperative Oncology Group; CI: Confidence interval; CRT: Chemoradiotherapy; HR: Hazard ratio.

Table 5 Types of surgical procedures performed in 65 patients with esophageal squamous cell carcinoma involving the lower third of the esophagus, n (%)

Type of surgery	With gastric invasion (n = 5)	Without gastric invasion (n = 60)
Esophagectomy with proximal gastrectomy	2 (40.0)	32 (53.3)
Video-assisted thoracoscopic esophagectomy with proximal gastrectomy	1 (20.0)	19 (31.7)
Robot-assisted esophagectomy with proximal gastrectomy	2 (40.0)	9 (15.0)

Table 6 Demographic and clinical characteristics of 23 patients with esophageal squamous cell carcinoma and direct gastric invasion according to treatment modality, n (%)

Variable	CRT (n = 15)	CRT followed by surgery (n = 5)	Supportive care (n = 3)	P value
Age in years (mean ± SD)	58.5 ± 9.9	57.2 ± 4.3	62.2 ± 14.1	0.65
< 58.1	7 (46.7)	3 (60.0)	1 (33.3)	> 0.99
≥ 58.1	8 (53.3)	2 (40.0)	2 (66.7)
Sex				0.35
Male	15 (100.0)	4 (80.0)	3 (100.0)
Female	0 (0.0)	1 (20.0)	0 (0.0)
T category				0.70
T2	1 (6.7)	0 (0.0)	0 (0.0)
T3	8 (53.3)	5 (100.0)	2 (66.7)
T4a	2 (13.3)	0 (0.0)	0 (0.0)
T4b	4 (26.7)	0 (0.0)	1 (33.3)
N category				0.07
N0	1 (6.7)	0 (0.0)	0 (0.0)
N1	7 (46.7)	1 (20.0)	0 (0.0)
N2	1 (6.7)	3 (60.0)	0 (0.0)
N3	6 (40.0)	2 (20.0)	3 (100.0)
M category				0.38
M0	10 (66.7)	5 (100.0)	2 (66.7)
M1	5 (33.3)	0 (0.0)	1 (33.3)
Clinical stage				0.49
II	2 (13.3)	0 (0.0)	0 (0.0)
III	5 (33.3)	4 (80.0)	1 (33.3)
IV	8 (53.3)	1 (20.0)	2 (66.7)
Histological grade				0.32
Grade 2, moderately differentiated	10 (66.7)	4 (80.0)	1 (33.3)
Grade 3, poorly differentiated	5 (33.3)	1 (20.0)	2 (66.7)
Tumor location				0.14
Upper to lower or middle to lower third of the esophagus	3 (20.0)	0 (0.0)	2 (66.7)
Lower third of the esophagus	12 (80.0)	5 (100.0)	1 (33.3)
Tumor length, cm (median, IQR)	9.0 (7.0–11.7)	7.0 (6.6–10.1)	13.0 (7.7–19)	0.22
Serum albumin, g/dL (mean ± SD)	3.9 ± 0.4	3.8 ± 0.8	3.62	0.68
ECOG performance status				0.13
0	0 (0.0)	2 (40.0)	0 (0.0)
1	12 (80.0)	4 (60.0)	2 (66.7)
2	3 (20.0)	0 (0.0)	1 (33.3)

Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher’s exact test. CRT: Chemoradiotherapy; ECOG: Eastern Cooperative Oncology Group; IQR: Interquartile range.