Cohort study to assess geographical variation in cholangiocarcinoma treatment in England

Table 1 Description of cholangiocarcinoma patients diagnosed between 2014 and 2017 in England, and subgroup who did not receive surgery up to 12 mo after diagnosis

Characteristics	Total	Did not receive surgery
Total patients (n, %)	8853 (100.0)	7751 (100.0)
Age at diagnosis (yr)
0-44	180 (2.0)	117 (1.5)
45-54	442 (5.0)	320 (4.1)
55-64	1231 (13.9)	962 (12.4)
65-74	2407 (27.2)	1963 (25.3)
75-84	2814 (31.8)	2615 (33.7)
> 84	1779 (20.1)	1774 (22.9)
Gender
Male	4343 (49.1)	3721 (48.0)
Female	4510 (50.9)	4030 (52.0)
Year of diagnosis
2014	2055 (23.2)	1802 (23.2)
2015	2213 (25.0)	1951 (25.2)
2016	2259 (25.5)	1983 (25.6)
2017	2326 (26.3)	2015 (26.0)
Route to diagnosis
Emergency presentation	4276 (48.3)	3975 (51.3)
TWW referral	1490 (16.8)	1306 (16.8)
Other GP referral	1844 (20.8)	1500 (19.4)
Other	979 (11.1)	729 (9.4)
Unknown	264 (3.0)	241 (3.1)
Stage at diagnosis
1	310 (3.5)	203 (2.6)
2	686 (7.7)	283 (3.7)
3	330 (3.7)	26 (2.9)
4	3506 (39.6)	3213 (41.5)
Missing	4021 (45.4)	3826 (49.4)
Tumour sub-type
CCA Other	391 (4.4)	378 (4.9)
eCCA	1595 (18.0)	1200 (15.5)
iCCA	6867 (77.6)	6173 (79.6)
Tumour morphology
Adenomas and adenocarcinomas	8570 (96.8)	7484 (96.6)
Other	283 (3.2)	267 (3.4)
English Index of Multiple Deprivation, income component
Quintile 1 (least deprived)	1715 (19.4)	1466 (18.9)
Quintile 2	1863 (21.0)	1609 (20.8)
Quintile 3	1797 (20.3)	1589 (20.5)
Quintile 4	1806 (20.4)	1590 (20.5)
Quintile 5 (most deprived)	1672 (18.9)	1497 (19.3)
Charlson comorbidity index
0	6220 (70.3)	5340 (68.9)
1	1140 (12.9)	1025 (13.2)
2	678 (7.7)	623 (8.0)
3+	815 (9.2)	763 (9.8)
Underlying liver disease
No	8044 (90.9)	7101 (91.6)
Yes	809 (9.1)	650 (8.4)
Cancer Alliance at diagnosis
Cheshire and Merseyside	427 (4.8)	358 (4.6)
East Midlands	795 (9.0)	703 (9.1)
East of England-North	524 (5.9)	478 (6.2)
East of England-South	558 (6.3)	476 (6.1)
Greater Manchester	521 (5.9)	453 (5.8)
Humber, Coast and Vale	310 (3.5)	269 (3.5)
Kent and Medway	251 (2.8)	226 (2.9)
Lancashire and South Cumbria	330 (3.7)	285 (3.7)
North Central London	141 (1.6)	119 (1.5)
North East London	173 (2.0)	150 (1.9)
North West and South West London	358 (4.0)	302 (3.9)
Northern	715 (8.1)	628 (8.1)
Peninsula	362 (4.1)	311 (4.0)
Somerset, Wiltshire, Avon and Gloucestershire	417 (4.7)	374 (4.8)
South East London	163 (1.8)	141 (1.8)
South Yorkshire and Bassetlaw	229 (2.6)	201 (2.6)
Surrey and Sussex	488 (5.5)	442 (5.7)
Thames Valley	234 (2.6)	202 (2.6)
Wessex	475 (5.4)	419 (5.4)
West Midlands	1013 (11.4)	883 (11.4)
West Yorkshire and Harrogate	369 (4.2)	331 (4.3)
Treatment received
Surgery only	507 (5.7)	0 (0.0)
Surgery + systemic therapy	367 (4.1)	0 (0.0)
Surgery + stent insertion	118 (1.3)	0 (0.0)
Surgery + systemic therapy + stent insertion	110 (1.2)	0 (0.0)
Systemic therapy only	1127 (12.7)	1127 (14.5)
Stent insertion only	1741 (19.7)	1741 (22.5)
Systemic therapy + stent insertion	415 (4.7)	415 (5.4)
None of surgery, systemic therapy or stent insertion	4468 (50.5)	4468 (57.6)

iCCA: Intrahepatic cholangiocarcinoma; eCCA: Extrahepatic cholangiocarcinoma; GP: General practitioner; TWW: Two week wait.

Table 2 Estimated percentage of cholangiocarcinoma patients in England 2014-2017 that received

	A: Potentially curative surgery				B: Systemic therapy in those who did not receive surgery				C: Stent insertion in those who did not receive surgery
	Unadjusted		Adjusted		Unadjusted		Adjusted		Unadjusted		Adjusted
	Estimate (95%CI)		Estimate 95%CI		Estimate (95%CI)		Estimate 95%CI		Estimate (95%CI)		Estimate 95%CI
Population average (intercept)	12.45	(11.76, 13.14)	12.45	(11.81, 13.09)	19.89	(19.01, 20.78)	19.89	(19.1, 20.69)	27.82	(26.85, 28.78)	27.82	(26.85, 28.78)
Cheshire and Merseyside	3.71	(0.32, 7.10)	3.77	(0.54, 6.99)	-1.18	(-5.13, 2.78)	-0.09	(-3.88, 3.70)	2.35	(-2.29, 6.99)	3.50	(-1.15, 8.16)
East Midlands	-0.88	(-3.00, 1.25)	-1.11	(-3.10, 0.87)	-0.12	(-2.93, 2.69)	-0.60	(-3.14, 1.93)	-1.93	(-5.02, 1.16)	-2.43	(-5.45, 0.60)
East of England - North	-3.67	(-6.05, -1.29)	-3.96	(-6.34, -1.59)	0.82	(-2.70, 4.34)	-0.06	(-3.17, 3.04)	13.40	(9.15, 17.65)	11.59	(7.44, 15.74)
East of England - South	2.25	(-0.59, 5.08)	1.33	(-1.36, 4.01)	-1.62	(-4.99, 1.76)	-2.70	(-5.68, 0.29)	9.79	(5.59, 13.98)	10.26	(6.14, 14.38)
Greater Manchester	0.60	(-2.20, 3.41)	-1.32	(-3.93, 1.29)	-0.03	(-3.59, 3.54)	0.86	(-2.38, 4.09)	0.88	(-3.16, 4.92)	-2.48	(-6.37, 1.40)
Humber, Coast and Vale	0.78	(-2.93, 4.49)	2.14	(-1.29, 5.58)	-0.56	(-5.21, 4.09)	0.78	(-3.33, 4.88)	-10.72	(-15.18, -6.25)	-10.32	(-14.62, -6.03)
Kent and Medway	-2.49	(-6.16, 1.19)	-2.14	(-5.75, 1.47)	-0.87	(-5.93, 4.19)	-0.77	(-5.43, 3.88)	3.60	(-2.38, 9.58)	4.51	(-1.43, 10.44)
Lancashire and South Cumbria	1.19	(-2.45, 4.82)	1.63	(-1.72, 4.98)	2.21	(-2.52, 6.94)	2.43	(-1.74, 6.60)	1.66	(-3.54, 6.86)	3.18	(-1.90, 8.25)
North Central London	3.16	(-2.84, 9.15)	2.36	(-3.22, 7.94)	9.52	(1.30, 17.73)	9.28	(1.76, 16.80)	3.28	(-5.08, 11.63)	3.18	(-4.95, 11.32)
North East London	0.85	(-4.19, 5.89)	-0.05	(-4.79, 4.69)	6.77	(-0.28, 13.82)	5.93	(-0.41, 12.26)	9.52	(1.80, 17.23)	10.48	(2.89, 18.06)
North West and South West London	3.19	(-0.48, 6.87)	2.68	(-0.79, 6.15)	7.26	(2.35, 12.17)	6.23	(2.02, 10.43)	-3.97	(-8.70, 0.75)	-3.16	(-7.84, 1.53)
Northern	-0.28	(-2.58, 2.02)	-0.10	(-2.20, 2.00)	2.40	(-0.71, 5.51)	2.52	(-0.35, 5.40)	-9.82	(-12.74, -6.90)	-9.63	(-12.58, -6.69)
Peninsula	1.64	(-1.87, 5.15)	1.72	(-1.43, 4.87)	-1.24	(-5.50, 3.01)	-0.01	(-3.76, 3.75)	5.95	(0.80, 11.09)	6.65	(1.64, 11.66)
Somerset, Wiltshire, Avon and Gloucestershire	-2.14	(-5.00, 0.73)	-1.37	(-4.02, 1.29)	-2.51	(-6.28, 1.25)	-1.97	(-5.34, 1.41)	8.82	(4.07, 13.57)	8.87	(4.14, 13.59)
South East London	1.05	(-4.19, 6.28)	2.51	(-2.6, 7.62)	2.09	(-4.74, 8.92)	3.20	(-2.82, 9.23)	-2.28	(-9.48, 4.91)	-2.08	(-9.08, 4.91)
South Yorkshire and Bassetlaw	-0.22	(-4.43, 3.98)	1.66	(-2.28, 5.59)	-7.46	(-12.01, -2.91)	-3.84	(-8.04, 0.35)	-1.45	(-7.49, 4.59)	-3.75	(-9.79, 2.29)
Surrey and Sussex	-3.02	(-5.56, -0.48)	-3.79	(-6.27, -1.30)	1.37	(-2.33, 5.07)	-0.76	(-4.14, 2.61)	13.59	(9.15, 18.02)	13.64	(9.22, 18.06)
Thames Valley	A1.23	(-3.13, 5.58)	0.07	(-3.96, 4.10)	4.36	(-1.49, 10.21)	2.00	(-3.52, 7.52)	-9.50	(-14.81, -4.19)	-8.26	(-13.63, -2.89)
Wessex	-0.66	(-3.49, 2.17)	-0.36	(-2.99, 2.27)	-0.32	(-4.02, 3.38)	-1.55	(-4.89, 1.80)	-1.09	(-5.21, 3.04)	-0.29	(-4.30, 3.72)
West Midlands	0.39	(-1.55, 2.32)	1.48	(-0.33, 3.29)	-4.49	(-6.77, -2.22)	-3.31	(-5.39, -1.24)	-11.73	(-14.08, -9.39)	-10.54	(-12.88, -8.20)
West Yorkshire and Harrogate	-2.15	(-5.20, 0.90)	-2.47	(-5.40, 0.46)	-0.26	(-4.45, 3.94)	-0.71	(-4.35, 2.92)	-4.86	(-9.31, -0.40)	-6.69	(-10.88, -2.50)
Age 0-44	22.14	(15.21, 29.08)	20.69	(13.91, 27.47)	37.29	(28.28, 46.31)	36.41	(27.47, 45.35)	-1.37	(-9.44, 6.70)	-1.59	(-9.41, 6.24)
Age 45-54	15.07	(11.03, 19.11)	13.24	(9.38, 17.11)	30.34	(24.98, 35.70)	28.96	(23.77, 34.15)	-4.91	(-9.47, -0.34)	-5.80	(-10.26, -1.34)
Age 55-64	9.38	(7.31, 11.46)	7.59	(5.58, 9.61)	23.18	(20.34, 26.03)	21.61	(18.82, 24.40)	-0.07	(-2.73, 2.59)	-0.39	(-3.00, 2.21)
Age 65-74	6.11	(4.86, 7.36)	4.84	(3.64, 6.04)	10.60	(8.94, 12.26)	9.59	(7.97, 11.21)	1.47	(-0.27, 3.21)	1.75	(0.06, 3.44)
Age 75-84	-5.41	(-6.29, -4.53)	-4.83	(-5.69, -3.96)	-8.88	(-9.95, -7.81)	-8.68	(-9.73, -7.63)	1.49	(0.07, 2.90)	1.53	(0.16, 2.90)
Age 85+	-12.21	(-12.9, -11.52)	-9.55	(-10.28, -8.83)	-19.18	(-20.05, -18.30)	-17.16	(-18.08, -16.23)	-2.81	(-4.6, -1.01)	-2.83	(-4.64, -1.02)
Female	-1.81	(-2.49, -1.13)	-0.49	(-1.13, 0.16)	-0.30	(-1.16, 0.56)	1.21	(0.43, 2.00)	-1.09	(-2.05, -0.12)	-1.18	(-2.13, -0.24)
Male	1.88	(1.17, 2.58)	0.51	(-0.16, 1.18)	0.33	(-0.60, 1.26)	-1.32	(-2.16, -0.47)	1.18	(0.13, 2.22)	1.28	(0.25, 2.31)
Income deprivation quintile 1 (least deprived)	2.12	(0.63, 3.61)	2.04	(0.64, 3.43)	3.15	(1.22, 5.08)	3.17	(1.41, 4.92)	0.98	(-1.11, 3.08)	0.47	(-1.59, 2.52)
Income deprivation quintile 2	1.23	(-0.15, 2.61)	1.17	(-0.11, 2.45)	1.44	(-0.34, 3.22)	1.88	(0.29, 3.47)	1.07	(-0.91, 3.04)	0.30	(-1.60, 2.20)
Income deprivation quintile 3	-0.90	(-2.24, 0.43)	-0.21	(-1.47, 1.05)	-0.21	(-1.96, 1.54)	0.24	(-1.32, 1.79)	1.14	(-0.85, 3.13)	0.66	(-1.26, 2.59)
Income deprivation quintile 4	-0.50	(-1.84, 0.85)	-0.38	(-1.63, 0.88)	-2.53	(-4.23, -0.84)	-2.32	(-3.85, -0.79)	-0.98	(-2.93, 0.98)	-1.08	(-2.98, 0.82)
Income deprivation quintile 5 (most deprived)	-2.03	(-3.38, -0.68)	-2.77	(-4.10, -1.43)	-1.70	(-3.48, 0.07)	-2.91	(-4.59, -1.22)	-2.28	(-4.28, -0.27)	-0.34	(-2.33, 1.65)
Diagnosis year 2014	-0.16	(-1.41, 1.08)	0.49	(-0.67, 1.65)	-1.46	(-3.05, 0.12)	0.08	(-1.35, 1.50)	-1.85	(-3.64, -0.06)	-1.81	(-3.53, -0.09)
Diagnosis year 2015	-0.64	(-1.81, 0.54)	-0.48	(-1.57, 0.61)	-0.77	(-2.29, 0.75)	-0.56	(-1.93, 0.81)	-0.55	(-2.27, 1.16)	-0.29	(-1.95, 1.36)
Diagnosis year 2016	-0.24	(-1.42, 0.93)	-0.30	(-1.41, 0.80)	0.69	(-0.85, 2.22)	0.08	(-1.29, 1.46)	0.82	(-0.90, 2.53)	1.04	(-0.62, 2.69)
Diagnosis year 2017	1.00	(-0.19, 2.20)	0.32	(-0.79, 1.43)	1.41	(-0.14, 2.95)	0.39	(-0.99, 1.77)	1.42	(-0.31, 3.14)	0.88	(-0.77, 2.53)
Adenomas and adenocarcinomas	0.23	(0.14, 0.32)	0.24	(0.14, 0.35)	0.49	(0.38, 0.59)	0.23	(0.10, 0.36)	-0.04	(-0.23, 0.15)	0.40	(0.18, 0.61)
Other morphology	-6.82	(-9.54, -4.10)	-7.35	(-10.55, -4.16)	-13.58	(-16.57, -10.59)	-6.38	(-10.05, -2.72)	1.08	(-4.31, 6.48)	-11.15	(-17.12, -5.18)
eCCA sub-type	12.40	(10.56, 14.23)	12.34	(10.58, 14.10)	1.64	(-0.50, 3.78)	2.89	(0.92, 4.87)	19.07	(16.51, 21.62)	19.28	(16.7, 21.86)
iCCA sub-type	-2.35	(-2.78, -1.93)	-2.65	(-3.09, -2.22)	0.10	(-0.35, 0.55)	-0.47	(-0.92, -0.02)	-3.66	(-4.20, -3.13)	-3.89	(-4.47, -3.31)
Other sub-type	-9.17	(-11.00, -7.33)	-3.70	(-6.01, -1.38)	-6.74	(-10.12, -3.36)	-1.52	(-4.98, 1.94)	-0.62	(-5.01, 3.78)	2.37	(-2.50, 7.24)
Emergency presentation diagnosis route	-5.45	(-6.14, -4.76)	-3.75	(-4.42, -3.08)	-7.95	(-8.80, -7.09)	-5.31	(-6.11, -4.51)	1.52	(0.55, 2.49)	2.10	(1.14, 3.07)
GP referral diagnosis route	6.16	(4.65, 7.68)	4.61	(3.17, 6.05)	6.10	(4.15, 8.04)	4.18	(2.39, 5.97)	-4.60	(-6.54, -2.65)	-5.28	(-7.16, -3.40)
IP and OP diagnosis route	13.04	(10.54, 15.55)	9.44	(7.09, 11.79)	12.54	(9.35, 15.73)	7.65	(4.69, 10.61)	-2.76	(-5.77, 0.25)	-2.75	(-5.69, 0.18)
TWW referral diagnosis route	-0.14	(-1.66, 1.37)	-0.58	(-2.08, 0.91)	10.96	(8.75, 13.18)	8.57	(6.55, 10.59)	2.92	(0.65, 5.19)	2.29	(0.06, 4.51)
Unknown diagnosis route	-2.99	(-7.06, 1.07)	-3.21	(-6.51, 0.08)	-5.61	(-10.73, -0.49)	-8.05	(-11.96, -4.15)	-5.21	(-11.31, 0.89)	-5.94	(-11.07, -0.81)
Charlson score - 0	1.69	(1.28, 2.10)	0.69	(0.30, 1.09)	3.19	(2.65, 3.73)	1.02	(0.51, 1.53)	1.52	(0.86, 2.18)	1.38	(0.73, 2.04)
Charlson score - 1	-2.31	(-3.98, -0.64)	-0.28	(-1.85, 1.29)	-3.40	(-5.56, -1.25)	0.42	(-1.52, 2.37)	-1.73	(-4.26, 0.80)	-2.00	(-4.45, 0.45)
Charlson score - 2	-4.32	(-6.35, -2.29)	-2.06	(-3.96, -0.17)	-6.06	(-8.71, -3.40)	-0.81	(-3.25, 1.63)	-1.97	(-5.30, 1.35)	-1.77	(-4.94, 1.40)
Charlson score - 3+	-6.07	(-7.74, -4.39)	-3.19	(-4.79, -1.60)	-12.84	(-14.71, -10.97)	-7.06	(-8.93, -5.20)	-6.73	(-9.52, -3.93)	-5.53	(-8.33, -2.74)
Liver disease-no	-0.73	(-0.99, -0.47)	-0.35	(-0.60, -0.10)	-0.51	(-0.80, -0.21)	0.04	(-0.25, 0.32)	0.46	(0.17, 0.75)	0.38	(0.10, 0.67)
Liver disease-yes	7.23	(4.65, 9.82)	3.47	(0.96, 5.97)	5.53	(2.33, 8.73)	-0.43	(-3.55, 2.69)	-4.99	(-8.11, -1.86)	-4.19	(-7.29, -1.08)

Apart from the intercept, estimates represent the percentage-point difference from the weighted cohort average probability of each route. CI: Confidence interval; iCCA: Intrahepatic cholangiocarcinoma; eCCA: Extrahepatic cholangiocarcinoma; GP: General Practitioner; IP: Inpatient; OP: Outpatient; TWW: Two week wait.