Adherence to Endoscopic Surveillance for Advanced Lesions and Colorectal Cancer in Inflammatory Bowel Disease

An AEG and GETECCU Collaborative Cohort Study

Maria Pilar Ballester; Francisco Mesonero; Pablo Flórez-Diez; Concepción Gómez; Esteban Fuentes-Valenzuela; Noelia Martín; Carla Senosiain; Milagros Vela; Agnes Fernández-Clotet; Pablo Pérez; Cristina Rubín de Célix; Cristina Calviño-Suárez; Benito Hermida; Roser Muñoz; Maria González-Vivo; Eduard Brunet; Nuria Jiménez; Belén Botella; Jorge Yebra; Cristina Suárez-Ferrer; Abdel Bouhmidi; Antonio López-Serrano; Ángel Ponferrada; Carmen Dueñas; Miguel Mínguez

Disclosures

Aliment Pharmacol Ther. 2022;55(11):1402-1413.

Abstract and Introduction

Abstract

Background and Aims: Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence.

Methods: A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant.

Results: A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24–29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3–10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462–5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409–7.644; p < 0.001 for intermediate- and high- vs low-risk groups).

Conclusions: Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

Introduction

Inflammatory bowel disease (IBD) is associated with an altered immune response in genetically pre-disposed subjects.^[1,2] Due to the inherent chronic mucosal inflammation, patients with colonic IBD have a twofold higher risk of colorectal cancer (CRC) than the general population.^[3] IBD CRC typically appears at an early age, in proximal locations, with a higher frequency of multiple and poorly differentiated lesions, representing a greater diagnostic challenge.^[4–6]

Several factors increase the risk of CRC, some related to IBD specifically, such as early age at diagnosis, longer disease duration, extent and severity of inflammation, presence of pseudopolyps or stenosis or coexistence of primary sclerosing cholangitis (PSC); and some found in the general population including smoking habit or CRC family history.^[7,8]

Endoscopic surveillance has been associated with reduced risk of advanced and interval neoplasia as well as the reduction in mortality from CRC in observational studies.^[9–11] Accordingly, several clinical guidelines have been developed for endoscopic surveillance of malignant or premalignant lesions in IBD.^[12–21] Nevertheless, only a few epidemiological studies have evaluated compliance with early detection programmes, showing poor adherence even in patients at high risk of CRC.^[22–25]

Given the lack of data in our setting, in agreement with previous studies, we hypothesised that adherence to clinical guidelines is low in Spain. The aims of our study were to evaluate: (i) adherence to endoscopic surveillance recommendations, (ii) impact of non-adherence on advanced lesions or CRC detection rate and (iii) risk factors associated with non-adherence.

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Table 1. Demographic and clinical characteristics of study population in the total cohort and in adherence and non-adherence groups
Variable	Results
Variable	Total (N = 1031)	Adherence (n = 274)	Non-adherence (n = 757)	p-value
Male	536 (52)	138 (51)	396 (53)	0.581
Smoking habit	427 (41)	123 (46)	304 (41)	0.173
Family history of CRC	45 (5)	10 (4)	35 (5)	0.499
PSC	27 (3)	6 (2)	21 (3)	0.604
Age at IBD diagnosis (years)	36 (15)	39 (15)	36 (15)	0.014
IBD type
UC	732 (71)	208 (76)	524 (69)	0.088
CD	259 (25)	59 (22)	200 (26)
Indeterminate	40 (4)	7 (3)	33 (4)
CD location
Ileal	5 (2)	1 (1)	4 (3)	0.989
Colonic	83 (32)	19 (32)	64 (32)
Ileocolonic	171 (66)	39 (66)	132 (66)
Upper disease^a	11 (4)	1 (2)	10 (5)
CD behaviour
Inflammatory	199 (77)	51 (86)	148 (74)	0.098
Stricturing	25 (9)	2 (3)	23 (12)
Penetrating	35 (14)	6 (10)	29 (15)
UC extent
Proctitis	14 (2)	3 (2)	11 (2)	0.144
Left-side colitis	348 (48)	88 (42)	260 (50)
Extensive colitis	370 (50)	117 (56)	253 (48)

Note: Continuous variables are presented as mean with standard deviation, categorical variables are presented as absolute and relative frequencies (%). Comparisons were performed using t-test for continuous and Chi-Square for categorical data.
Abbreviations: CRC, Colorectal cancer; PSC, primary sclerosing cholangitis; IBD, Inflammatory Bowel Disease; UC, Ulcerative colitis; CD, Crohn's disease.
^aL4 was a modifier added to L1-L3 when concomitant upper disease was present.

Table 2. Distribution of patients according to hospital characteristics in the total cohort and in adherence and non-adherence groups
Variable	Results
Variable	Total (N = 1031)	Adherence (n = 274)	Non-adherence (n = 757)	p-value
Hospital type
Tertiary	234 (23)	217 (79)	580 (77)	0.383
Regional	797 (77)	57 (21)	177 (23)	0.383
Specialised IBD Unit	1004 (97)	269 (98)	735 (97)	0.337
Accredited IBD Unit	796 (77)	215 (79)	581 (77)	0.562
Number of IBD consultations per year
<500	42 (4)	8 (3)	34 (5)	0.488
500–1500	288 (28)	80 (29)	208 (28)
>1500	701 (68)	186 (68)	515 (68)
Number of IBD endoscopies per year
<400	393 (38)	93 (34)	300 (40)	0.003
400–800	239 (23)	49 (18)	190 (25)
>800	399 (39)	132 (48)	267 (35)
Population CRC screening programme	990 (96)	257 (94)	733 (97)	0.028
Specific IBD endoscopy room	311 (30)	88 (32)	223 (30)	0.411
Specialised endoscopist	426 (41)	115 (42)	311 (41)	0.798

Note: Variables are presented as absolute and relative frequencies (%). Comparisons were performed using chi-Squared test.
Abbreviations: CRC, colorectal cancer; IBD, inflammatory bowel disease.

Table 3. Characteristics of surveillance colonoscopies
Variable	Results
Variable	First procedure (n = 888)	Follow-up (n = 478)
Repeated colonoscopy	55 (6)	29 (6)
Poor preparation	37 (4)	18 (4)
Inflammatory activity	13 (2)	11 (2)
Procedural complications	5 (1)	0 (0)
Complete visualisation of the colon	840 (95)	448 (94)
Detection technique
White light	667 (75)	295 (62)
Chromoendoscopy	221 (25)	183 (38)
Biopsy protocol
Random	493 (56)	227 (47)
Targeted	177 (20)	97 (20)
No biopsies	218 (24)	154 (32)
Cleaning scale
Boston ≥6	840 (95)	445 (93)
Boston <6	48 (5)	33 (7)
Inflammatory activity	270 (31)	166 (35)
Mild	159 (18)	121 (25)
Moderate	101 (11)	41 (9)
Severe	10 (1)	4 (1)
Endoscopic lesions
Visible	207 (23)	105 (22)
Invisible	9 (1)	6 (1)

Note: Variables are presented as absolute and relative frequencies (%).

Table 4. Demographic and clinical risk factors of advanced lesions
Variable	Univariable analysis			Multivariable analysis
Variable	HR	95% CI	p-value	HR	95% CI	p-value
Male/Female	1.8	0.9–3.5	0.093
Smoking habit	1.2	0.6–2.2	0.640
Family history of CRC	1.9	0.6–6.2	0.292
PSC	1.02	0.1–7.5	0.983
Age at IBD diagnosis (yr)	1.1	1.03–1.1	<0.001	1.1	1.03–1.1	<0.001
IBD type
CD	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
UC	6.3	1.5–26.2	0.011	3.9	0.9–16.4	0.063
Indeterminate	3.3	0.3–35.9	0.335	2.1	0.2–23.3	0.549
CD location
Ileal	Ref.	Ref.	Ref.
Colonic	1.0	0.0–6096	1.000
Ileocolonic	39.1	0.0–5358	0.888
CD behaviour
Inflammatory	Ref.	Ref.	Ref.
Stricturing	0.03	0.0–8415	0.758
Penetrating	0.03	0.0–2985	0.715
UC extent
Proctitis	Ref.	Ref.	Ref.
Left-side colitis	0.5	0.1–3.8	0.503
Extensive colitis	0.9	0.1–6.4	0.881
Risk group
Low	Ref.	Ref.	Ref.	Ref.	Ref.	Ref.
Intermediate	2.2	1.1–4.6	0.032	2.2	1.1–4.6	0.032
High	6.2	2.7–14.2	<0.001	6.2	2.7–14.4	<0.001
Adherence (vs delay or non-performance of endoscopic surveillance)	3.6	1.3–10.1	0.016	3.3	1.1–9.3	0.028

Note: Analyses were performed using Cox-regression univariable and multivariable test.
Abbreviations: CD, Crohn's disease; CRC, colorectal cancer; IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis; ref, reference; UC, ulcerative colitis.

Table 5. Demographic and clinical risk factors of CRC
Variable	Univariable analysis			Multivariable analysis
Variable	HR	95% CI	p-value	HR	95% CI	p-value
Male/Female	1.1	0.3–3.5	0.899
Smoking habit	1.3	0.4–4.6	0.646
Family history of CRC	2.3	0.3–18.1	0.431
PSC	13.9	3.7–52	<0.001	7.4	1.2–47.6	0.034
Age at IBD diagnosis (year)	1.1	1.02–1.1	0.003	1.1	1.02–1.1	0.007
IBD type
CD	Ref.	Ref.	Ref.
UC	34.8	0.1–12747	0.238
Indeterminate	0.9	0.0–640015	1.000
CD location
Ileal	—	—	—
Colonic
Ileocolonic
CD behaviour
Inflammatory	—	—	—
Stricturing
Penetrating
UC extent
Proctitis	Ref.	Ref.	Ref.
Left-side colitis	1900	0.0–7242	0.951
Extensive colitis	4716	0.0–1795	0.945
Risk group
Low	Ref.	Ref.	—	Ref.	Ref.	—
Intermediate	0.8	0.1–7.4	0.817	0.6	0.1–5.8	0.656
High	16.6	3.9–69.4	<0.001	5.4	0.9–31.4	0.059
Adherence (vs delay or non-performance of endoscopic surveillance)	1.1	0.3–4.1	0.898

Note: Analyses were performed using Cox-regression univariable and multivariable test. No cases were available for analyses in CD location or behaviour.
Abbreviations: CD, Crohn's disease; CRC, colorectal cancer; IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis; ref, reference; UC, Ulcerative colitis.

Authors and Disclosures

Maria Pilar Ballester¹, Francisco Mesonero², Pablo Flórez-Diez³, Concepción Gómez¹, Esteban Fuentes-Valenzuela⁴, Noelia Martín⁵, Carla Senosiain², Milagros Vela⁶, Agnes Fernández-Clotet⁷, Pablo Pérez⁸, Cristina Rubín de Célix⁹, Cristina Calviño-Suárez¹⁰, Benito Hermida¹¹, Roser Muñoz¹², Maria González-Vivo¹³, Eduard Brunet¹⁴, Nuria Jiménez¹⁵, Belén Botella¹⁶, Jorge Yebra¹⁷, Cristina Suárez-Ferrer¹⁸, Abdel Bouhmidi¹⁹, Antonio López-Serrano²⁰, Ángel Ponferrada²¹, Carmen Dueñas²² and Miguel Mínguez¹, Young Group of AEG and GETECCU

¹Digestive Disease Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
²Digestive Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
³Digestive Disease Department, Hospital Universitario Central de Asturias, Asturias, Spain
⁴Digestive Disease Department, Hospital Universitario Rio Hortega Valladolid, Valladolid, Spain
⁵Digestive Disease Department, Hospital de Galdakao, Bizkaia, Spain
⁶Digestive Disease Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
⁷Gastroenterology Department, IBD Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
⁸Digestive Disease Department, Hospital Provincial de Pontevedra, Pontevedra, Spain
⁹Digestive Disease Department, Hospital de La Princesa, Madrid, Spain
¹⁰Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
¹¹Digestive Disease Department, Hospital Universitario de Cabueñes, Asturias, Spain
¹²Digestive Disease Department, Hospital General de Alicante, Alicante, Spain
¹³Gastroenterology Department, Hospital del Mar, Barcelona, Spain
¹⁴Digestive Disease Department, Hospital Parc Taulí, Sabadell, Spain
¹⁵Digestive Disease Department, Hospital General Universitario de Elche, Elche, Spain
¹⁶Digestive Disease Department, Hospital Universitario Infanta Cristina, Madrid, Spain
¹⁷Digestive Disease Department, Hospital Universitario de Móstoles, Madrid, Spain
¹⁸Digestive Disease Department, Hospital La Paz, Madrid, Spain
¹⁹Digestive Disease Department, Hospital Santa Bárbara Puertollano, Puertollano, Spain
²⁰Digestive Disease Department, Hospital Doctor Peset, Valencia, Spain
²¹Digestive Disease Department, Hospital Universitario Infanta Leonor, Madrid, Spain
²²Digestive Disease Department, Hospital Universitario de Cáceres, Cáceres, Spain

Correspondence
Maria Pilar Ballester, Digestive Disease Department. Hospital Clínico Universitario de Valencia. Blasco Ibáñez, 17, 46010, Valencia, Spain. Email: mapibafe@gmail.com

Author contributions
Ballester MP, Mesonero F and Minguez M were involved in study concept and design, data analysis and interpretation of the manuscript. Ballester MP also carried out drafting of the manuscript. All authors carried out acquisition of data, critical revision of the manuscript and approved the final version of the manuscript.

Appendix 2

The Complete List of Author Names and Their Affiliations

Maria Pilar Ballester, Concepción Gómez and Miguel Mínguez, Digestive Disease Department, Hospital Clínico Universitario de Valencia, Universitat de València, Valencia, Spain; Francisco Mesonero and Carla Senosiain, Francisco Mesonero, Digestive Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain; Pablo Flórez-Diez, Digestive Disease Department, Hospital Universitario Central de Asturias, Asturias, Spain; Esteban Fuentes-Valenzuela, Digestive Disease Department, Hospital Universitario Rio Hortega Valladolid, Spain; Noelia Martín, Digestive Disease Department, Hospital de Galdakao Bizkaia, Spain; Milagros Vela, Digestive Disease Department, Hospital Universitario Nuestra Señora de Candelaria Santa Cruz de Tenerife, Spain; Agnes Fernández-Clotet, Gastroenterology Department, IBD Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain; Pablo Pérez, Digestive Disease Department, Hospital Provincial de Pontevedra Pontevedra, Spain; Cristina Rubín de Célix, Digestive Disease Department, Hospital de La Princesa, Madrid, Spain; Cristina Calviño-Suárez, Digestive Disease Department, Hospital Clínico Universitario de Santiago Santiago de Compostela, Spain; Benito Hermida, Digestive Disease Department, Hospital Universitario de Cabueñes Asturias, Spain; Roser Muñoz, Digestive Disease Department, Hospital General de Alicante Alicante, Spain; Maria González-Vivo, Gastroenterology Department, Hospital del Mar, Barcelona, Spain; Eduard Brunet, Digestive Disease Department, Hospital Parc Taulí, Sabadell, Spain; Nuria Jiménez, Digestive Disease Department, Hospital General Universitario de Elche, Alicante, Spain; Belén Botella, Digestive Disease Department, Hospital Universitario Infanta Cristina Madrid, Spain; Jorge Yebra, Digestive Disease Department, Hospital Universitario de Móstoles, Madrid, Spain; Cristina Suárez-Ferrer, Digestive Disease Department, Hospital La Paz, Madrid, Spain; Abdel Bouhmidi, Digestive Disease Department, Hospital Santa Bárbara Puertollano, Puertollano, Spain; Antonio López-Serrano, Digestive Disease Department, Hospital Doctor Peset, Valencia, Spain; Ángel Ponferrada, Digestive Disease Department, Hospital Universitario Infanta Leonor, Madrid, Spain; Carmen Dueñas, Digestive Disease Department, Hospital Universitario de Cáceres Cáceres, Spain; On behalf of Young Group of AEG and GETECCU, Digestive Disease Department, Hospital Universitario Reina Sofía and IMIBIC Córdoba, Córdoba, Spain, Digestive Disease Department, Hospital Sant Jaume de Calella Calella, Spain; Digestive Disease Department, Hospital Comarcal de Inca Inca, Spain; Digestive Disease Department, Hospital Universitario y Politécnico La Fe Valencia, Spain.