Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

Table 1 Definition of study groups n (%)

Total study population	n = 825
No treatment	497 (60.2)
Treatment groups
Chemotherapy	153 (18.5)
Chemoradiation	61 (7.4)
Surgery	114 (13.8)
Surgical subgroups
Surgery alone	69 (60.5)
Adjuvant radiation	4 (3.5)
Adjuvant chemotherapy	20 (17.5)
Adjuvant chemoradiation	21 (18.4)

The 825 patients included in this study were categorized by type of treatment received. Treatment groups were divided into chemotherapy, chemoradiation, and surgical groups. The surgical group was then subdivided into surgery alone, surgery with adjuvant chemotherapy, and surgery with adjuvant chemoradiation.

Table 2 Characteristics of patient and treatment groups n (%)

	Chemo only (n = 153 )	Chemoradiation (n = 61)	Surgery (n = 114 )	P value
Age group (yr)				< 0.0001
18-49	29 (19.0)	10 (16.4)	29 (25.4)
50-64	62 (40.5)	20 (32.8)	44 (38.6)
65-79	55 (35.9)	31 (50.8)	39 (34.2)
≥ 80	7 (4.6)	0 (0.0)	2 (1.8)
Sex				0.000
Men	57 (37.3)	36 (59.0)	69 (60.5)
Women	96 (62.7)	25 (41.0)	45 (39.5)
Race				0.002
Non-hispanic white	74 (48.4)	26 (42.6)	53 (46.5)
Black	9 (5.9)	7 (11.5)	4 (3.5)
Hispanic white	37 (24.2)	8 (13.1)	29 (25.4)
Other	33 (21.6)	20 (32.8)	28 (24.6)
Socioeconomic status				0.046
Highest	38 (24.8)	18 (29.5)	33 (28.9)
Middle	96 (62.7)	35 (57.4)	65 (57.0)
Lowest	19 (12.4)	8 (13.1)	16 (14.0)
Tumor				0.000
Liver	21 (13.7)	3 (4.9)	22 (19.3)
Location
Bile duct	132 (86.3)	58 (95.1)	92 (80.7)
Grade				0.685
Well differentiated	12 (19.4)	4 (17.4)	19 (21.1)
Moderately differentiated	20 (32.3)	5 (21.7)	33 (36.7)
Poorly differentiated	30 (48.4)	14 (60.9)	38 (42.2)
Tumor size (cm)				0.060
≤ 5	10 (27.8)	7 (58.3)	34 (50.0)
> 5	26 (72.2)	5 (41.7)	34 (50.0)
Summary				0.000
Local	17 (15.3)	9 (21.4)	35 (36.1)
Stage
Regional	29 (26.1)	16 (38.1)	36 (37.1)
T stage				0.001
T1	23 (24.5)	8 (19.5)	37 (37.4)
T2	2 (2.1)	3 (7.3)	14 (14.1)
T3	19 (20.2)	10 (24.4)	18 (18.2)
T4	50 (53.2)	20 (48.8)	30 (30.3)
N stage				0.211
N0	53 (72.6)	22 (68.8)	71 (79.8)
N1	20 (27.4)	10 (31.3)	18 (20.2)
M stage				< 0.0001
M0	60 (46.9)	32 (68.1)	96 (87.3)
M1	68 (53.1)	15 (31.9)	14 (12.7)
AJCC7 stage				< 0.0001
I	13 (14.4)	2 (6.3)	34 (36.6)
II	1 (1.1)	2 (6.3)	9 (9.7)
III	18 (11.8)	7 (11.5)	23 (20.2)
IV	58 (64.4)	21 (65.6)	27 (29.1)
Chemotherapy	153 (100.0)	61 (100.0)	41 (36.0)	< 0.0001
Radiation	0 (0.0)	61 (100.0)	25 (21.9)	< 0.0001

In general, characteristics that were different between the surgical patients and the non-surgical patients were age, gender, tumor location, and stage. Patients in the surgery cohort were more often male, white, and young. chemo: Chemotherapy; AJCC: American Joint Committee on Cancer.

Table 3 Characteristics of surgical groups n (%)

	Surgery alone (n = 69)	Adjuvant chemotherapy (n = 20)	Adjuvant chemoradiation (n = 21)	P value
Age group (yr)				< 0.0001
18-49	13 (18.8)	6 (30.0)	10 (47.6)
50-64	29 (42.0)	6 (30.0)	7 (33.3)
65-79	25 (36.2)	8 (40.0)	4 (19.0)
≥ 80	2 (2.9)	0 (0.0)	0 (0.0)
Sex				0.018
Men	41 (59.4)	13 (65.0)	14 (66.7)
Women	28 (40.6)	7 (35.0)	7 (33.3)
Race				0.497
Non-hispanic white	33 (47.8)	11 (55.0)	9 (42.9)
Black	2 (2.9)	0 (0.0)	2 (9.5)
Hispanic white	20 (29)	3 (15.0)	5 (23.8)
Other	14 (20.3)	6 (30.0)	5 (23.8)
Socioeconomic status				0.603
Highest	18 (26.1)	7 (35.0)	7 (33.3)
Middle	41 (59.4)	9 (45.0)	12 (57.1)
Lowest	10 (14.5)	4 (20.0)	2 (9.5)
Tumor				0.000
Liver	17 (24.6)	3 (15.0)	2 (9.5)
Location
Bile duct	52 (75.4)	17 (85.0)	19 (90.5)
Grade				0.684
Well differentiated	13 (23.6)	3 (20.0)	3 (16.7)
Moderately differentiated	21 (38.2)	4 (26.7)	6 (33.3)
Poorly differentiated	21 (38.1)	8 (53.3)	9 (50.0)
Tumor size (cm)				0.825
≤ 5	24 (54.5)	3 (25.0)	6 (60.0)
> 5	20 (45.5)	9 (75.0)	4 (40.0)
Summary				0.016
Local	23 (38.3)	3 (20.0)	7 (38.9)
Stage
Regional	24 (40.0)	5 (33.3)	6 (33.3)
Distant	13 (21.7)	7 (46.7)	5 (27.8)
T stage				0.071
T1	24 (40.0)	5 (29.4)	7 (36.8)
T2	9 (15.0)	3 (17.6)	2 (10.5)
T3	12 (20.0)	3 (17.6)	3 (15.8)
T4	15 (25.0)	6 (35.3)	7 (36.8)
N stage				0.396
N0	44 (83.0)	10 (62.5)	14 (82.4)
N1	9 (17.0)	6 (37.5)	3 (17.6)
AJCC7 stage				< 0.0001
I	22 (40.0)	5 (29.4)	6 (33.3)
II	7 (12.7)	1 (5.9)	1 (5.6)
III	13 (23.6)	3 (17.7)	5 (27.8)
IV	13 (23.7)	8 (47.0)	6 (33.4)

Characteristics found to be significantly different between surgical patients were age, gender, tumor location, and stage. Patients in the adjuvant chemoradiation group were male and much younger in age compared to the other groups. AJCC: American Joint Committee on Cancer.

Table 4 Univariate and stepwise analysis for overall survival n (%)

		Univariate hazard ratio (95%CI)	Stepwise hazard ratio (95%CI)
Age1 (yr)
18-49	107 (13.0)	1.00 (reference)	1.00 (reference)
50-64	230 (27.9)	1.43 (1.11-1.85)	1.64 (1.27-2.13)
65-79	327 (39.6)	1.40 (1.10-1.78)	1.47 (1.15-1.89)
≥ 80	161 (19.5)	2.19 (1.68-2.86)	1.85 (1.40-2.46)
Sex1
Men	390 (47.3)	1.00 (reference)
Women	435 (52.7)	1.02 (0.88-1.18)
Race
Non-hispanic white	373 (45.2)	1.00 (reference)
Ethnicity1
Black	64 (7.8)	1.50 (1.14-1.97)
Hispanic white	215 (26.1)	1.04 (0.87-1.24)
Other	170 (20.6)	1.00 (0.82-1.21)
Socioeconomic status1
Highest	184 (22.3)	1.00 (reference)	1.00 (reference)
Middle	497 (60.2)	1.25 (1.04-1.49)	1.18 (0.98-1.41)
Lowest	144 (17.5)	1.61 (1.28-2.03)	1.52 (1.20-1.92)
Grade
Well differentiated	52 (6.3)	1.00 (reference)
Moderately differentiated	99 (12.0)	1.05 (0.72-1.53)
Poorly differentiated	135 (16.4)	1.61 (1.13-2.29)
Undifferentiated	8 (1.0)	2.96 (1.38-6.32)
Unknown	531 (64.4)	1.71 (1.24-2.35)
Tumor size (cm)
≤ 5	95 (11.5)	1.00 (reference )
> 5	94 (11.4)	1.03 (0.76-1.39)
T Stage
T1	150 (18.2)	1.00 (reference)
T2	28 (3.4)	0.91 (0.57-1.47)
T3a	64 (7.8)	1.10 (0.80-1.51)
T3b	13 (1.6)	1.37 (0.72-2.63)
T4	198 (24)	2.23 (1.76-2.83)
TX	372 (45.1)	1.85 (1.50-2.29)
N stage
N0	278 (33.7)	1.00 (reference )
N1	77 (9.3)	1.62 (1.24-2.12)
NX	470 (57)	1.76 (1.50-2.07)
AJCC7 group1
I	93 (11.3)	1.00 (reference)	1.00 (reference)
II	15 (1.8)	0.80 (0.41-1.56)	1.07 (0.54-2.09)
III	79 (9.6)	1.37 (0.98-1.91)	1.31 (0.93-1.84)
IV	204 (24.7)	2.81 (2.11-3.72)	2.56 (1.90-3.44)
Unknown	434 (52.6)	2.23 (1.72-2.89)	1.52 (1.16-2.00)
Treatment groups
Chemo alone	153 (18.5)	1.00 (reference)
Chemoradiation	61 (7.4)	0.98 (0.72-1.34)
Surgery	114 (13.8)	0.44 (0.34-0.59)
None	497 (60.2)	1.50 (1.24-1.81)
Surgery groups
Surgery Alone	69 (8.4)	1.00 (reference)
Adjuvant chemo	20 (2.4)	1.44 (0.82-2.55)
Adjuvant chemoradiation	21 (2.5)	1.02 (0.56-1.85)
Adjuvant radiation	4 (0.5)	1.53 (0.55-4.26)
No surgery	711 (86.2)	3.19 (2.35-4.33)
Surgery1
No	711 (86.2)	1.00 (reference )	1.00 (reference )
Yes	114 (13.7)	0.34 (0.27-0.43)	0.42 (0.32-0.54)
Chemo1
No	570 (69.1)	1.00 (reference )	1.00 (reference )
Yes	255 (30.9)	0.73 (0.62-0.85)	0.70 (0.59-0.83)
Radiation1
No	707 (85.7)	1.00 (reference )
Yes	118 (14.3)	0.74 (0.60-0.90)

¹Included in step-wise model. On univariate analysis, older age, black race, lower socioeconomic status, undifferentiated tumors, and T4 tumors were significantly associated with poorer survival. Upon stepwise analysis, older age (> 80 year), advanced disease stage, poorly differentiated or undifferentiated tumors, and lymph node involvement were independent predictors of poorer survival in all treatment groups. There was a significant improvement in survival associated with surgical resection and receipt of chemotherapy. chemo: Chemotherapy; AJCC: American Joint Committee on Cancer.