Incidence of Interval Colorectal Cancer Among Inflammatory Bowel Disease Patients Undergoing Regular Colonoscopic Surveillance

doi:10.1016/j.cgh.2015.04.183

Clinical Gastroenterology and Hepatology

Volume 13, Issue 9, September 2015, Pages 1656-1661

https://doi.org/10.1016/j.cgh.2015.04.183 Get rights and content

Background & Aims

Surveillance is recommended for patients with long-term inflammatory bowel disease because they have an increased risk of colorectal cancer (CRC). To study the effectiveness of surveillance, we determined the incidence of CRC after negative findings from surveillance colonoscopies (interval CRC).

Methods

We collected data from 1273 patients with ulcerative colitis or Crohn's disease, enrolled in a surveillance program at 7 hospitals in The Netherlands, who underwent 4327 surveillance colonoscopies from January 1, 2000, through January 1, 2014. Patients were followed up from their first surveillance colonoscopy until the last surveillance colonoscopy, colectomy, or CRC. Factors that might have contributed to the occurrence of CRC were categorized as inadequate procedures (ie, inadequate bowel preparation), inadequate surveillance (CRC occurring outside the appropriate surveillance interval), or inadequate management of dysplasia (CRC diagnosed in the same colonic segment as a previous diagnosis of dysplasia). The remaining CRC cases were classified as true interval CRCs.

Results

CRC was diagnosed in 17 patients (1.3%), with an incidence of 2.5 per 1000 years of follow-up evaluation. Factors that might account for the occurrence of CRC were identified in 12 patients (70%). These were inadequate colonoscopies in 4 patients (24%), inadequate surveillance intervals in 9 patients (53%), and inadequate management of dysplasia in 2 patients (12%). The remaining 5 cases of CRC (30%) were classified as true interval CRCs.

Conclusions

In a retrospective analysis of patients with inflammatory bowel disease participating in a surveillance program, the incidence of CRC was only 1%, which supports the implementation of longer surveillance intervals. However, the fact that 30% of CRC cases were interval cancers indicates the need for variable surveillance intervals based on risk factors for CRC.

Section snippets

Patients

All patients with a diagnosis of CD or UC from 5 university hospitals and 2 general hospitals were identified using the diagnosis treatment combinations (DTCs) for IBD. DTCs are based on the International Classification of Diseases codes and can be considered the Dutch version of the Diagnosis Related Groups, as used in other countries (eg, the United States).

The medical records and endoscopy reports of all patients with a DTC code for CD or UC were reviewed to confirm the IBD diagnosis and to

Surveillance Cohort

A total of 1273 IBD patients were identified who were enrolled in a surveillance program, of whom 434 patients had CD (34%), 804 had UC (63%), and 35 had IBD unclassified (3%). Baseline characteristics are shown in Table 1.

During a mean follow-up period of 5.3 years (±3.0 y), 4327 surveillance colonoscopies were performed in the study population, comprising 6823 years of follow-up evaluation. Surveillance was performed with random biopsy sampling in 3887 procedures (90%), during which a mean of

Discussion

This study shows that the incidence of CRC among IBD patients enrolled in a surveillance program is low compared with previous studies, with only 17 cancers detected during 6823 years of follow-up evaluation.⁸

The majority of CRC cases (70%) could be explained by an inadequate surveillance procedure before the CRC diagnosis (ie, inadequate bowel preparation), inadequate surveillance interval, or inadequate dysplasia management. This suggests that the incidence of CRC could have been even lower

References (21)

A. Ekbom et al.
Increased risk of large-bowel cancer in Crohn's disease with colonic involvement
Lancet
(1990)
F.A. Farraye et al.
AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease
Gastroenterology
(2010)
S. Sanduleanu et al.
Interval colorectal cancers in inflammatory bowel disease: the grim statistics and true stories
Gastrointest Endosc Clin N Am
(2014)
M.D. Rutter et al.
Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis
Gastroenterology
(2006)
F.S. Velayos et al.
Prevalence of colorectal cancer surveillance for ulcerative colitis in an integrated health care delivery system
Gastroenterology
(2010)
J.A. Eaden et al.
How gastroenterologists screen for colonic cancer in ulcerative colitis: an analysis of performance
Gastrointest Endosc
(2000)
K. Leung et al.
Ongoing colorectal cancer risk despite surveillance colonoscopy: the Polyp Prevention Trial Continued Follow-up Study
Gastrointest Endosc
(2010)
R. Kiesslich et al.
Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis
Gastroenterology
(2003)
V. Annese et al.
European evidence based consensus for endoscopy in inflammatory bowel disease
J Crohns Colitis
(2013)
A. Ekbom et al.
Ulcerative colitis and colorectal cancer. A population-based study
N Engl J Med
(1990)

There are more references available in the full text version of this article.

Cited by (66)

Colorectal Cancer Screening in Inflammatory Bowel Diseases—Can Characterization of GI Microbiome Signatures Enhance Neoplasia Detection?
2022, Gastroenterology
Current noninvasive methods for colorectal cancer (CRC) screening are not optimized for persons with inflammatory bowel diseases (IBDs), requiring patients to undergo frequent interval screening via colonoscopy. Although colonoscopy-based screening reduces CRC incidence in IBD patients, rates of interval CRC remain relatively high, highlighting the need for more targeted approaches. In recent years, the discovery of disease-specific microbiome signatures for both IBD and CRC has begun to emerge, suggesting that stool-based biomarker detection using metagenomics and other culture-independent technologies may be useful for personalized, early, noninvasive CRC screening in IBD patients. Here we discuss the utility of the stool microbiome as a noninvasive CRC screening tool. Comparing the performance of multiple microbiome-based CRC classifiers, including several multi-cohort meta-analyses, we find that noninvasive detection of colorectal adenomas and carcinomas from microbial biomarkers is an active area of study with promising early results.
Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis
2022, Gastroenterology
Citation Excerpt :
Concomitant use of imaging modalities and select biomarkers, such as liquid biopsies, or mutational analysis of pancreatic juice,38 is currently a research area that may improve the surveillance efficiency. The data on interval CRC progression can also provide us with some guidance on the issue of late-stage PDACs in high-risk surveillance program imaging.4,5 Errors in follow-up intervals, dysplasia management, and suboptimal quality of colonoscopy are common factors implicated in interval CRC progression.
Identification and resection of successful targets, that is, T₁ N₀M₀ pancreatic ductal adenocarcinoma (PDAC) and high-grade precursors during surveillance of high-risk individuals (HRIs) confers improved survival. Late-stage PDACs refer to T_2–4 N₀M₀ and nodal or distant metastatic PDAC stages diagnosed during the follow-up phase of HRI surveillance. This study aimed to quantify late-stage PDACs during HRI surveillance and identify associated clinicoradiologic factors.
A systematic search (PROSPERO:CRD42018117189) from Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science was last performed on April 18, 2021. Only original HRI surveillance manuscripts that specified follow-up strategies were included, and studies with only baseline information were excluded. Cumulative incidences of advanced neoplasia: high-grade precursors and all PDACs, and surveillance-detected/interval late-stage PDACs were calculated through random-effects model. Incidence of late-stage PDACs underwent metaregression to identify association with HRI clinicoradiologic features. Publication bias was assessed through the funnel plot and Egger’s regression line.
Thirteen original surveillance studies included 2169 HRIs followed over 7302.72 patient-years. Cumulative incidence of advanced neoplasia and late-stage PDACs was 3.3 (95% confidence interval [CI]: 0.6–7.4) and 1.7 (95% CI: 0.2–4.0) per 1000 patient-years, respectively. Late-stage PDACs lacked significant association with surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Limited information on diagnostic error, symptoms, timing of presentation, lesion site, and surveillance adherence precluded formal meta-analysis.
A sizeable proportion of late-stage PDACs were detected during follow-up. Their incidence lacked association with baseline clinicoradiologic features. Further causal investigation of stage-based outcomes is warranted for overall improvement in HRI surveillance.
Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management
2022, Gastroenterology
Citation Excerpt :
All risk-stratification algorithms rely on clinical factors, many of which have come under scrutiny based on more recent, robust data demonstrating null associations with aCRN risk (eg, inflammation on the immediately preceding colonoscopy, pseudopolyps, and strictures).45 The nonpersonalized approach for determining timing of screening initiation and subsequent surveillance intervals is potentially missing a sizable proportion of people who develop CRC before screening initiation, and possibly over-surveilling individuals at lower risk than previously considered.45,56,80,81 One multi-center study demonstrated an extremely low risk of subsequent aCRN over a median 6.1 years of follow-up in patients with IBD colitis undergoing surveillance who had at least 2 consecutive colonoscopies demonstrating histologically quiescent disease and in the absence of high-risk features (PSC, family history of CRC).82
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Colitis-associated CRC shares many molecular similarities with sporadic CRC, and preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC). Some unique molecular differences occur in CAC, but their role in the pathogenesis and behavior of inflammation-associated cancers remains to be elucidated. Nonconventional types of dysplasia have been increasingly recognized, but their natural history is not well defined, and they have not been incorporated into surveillance algorithms. The concept of cumulative inflammatory burden highlights the importance of considering histologic inflammation over time as an important risk factor for CAC. Dysplasia is arguably the most important risk factor for developing CAC, and advances have been made in the endoscopic detection and removal of precancerous lesions, thereby deferring or avoiding surgical resection. Some of the agents used to treat IBD are chemopreventive. It is hoped that by gaining better control of the underlying inflammation with newer medications and better endoscopic detection and management, a more sophisticated appreciation of clinicopathologic risk factors, and growing awareness of the genetic, immunologic, and environmental causes of colitis- associated neoplasia, that colitis-associated colorectal neoplasia will become even more predictable and manageable in the coming years.
Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives
2021, European Journal of Internal Medicine
Citation Excerpt :
This is underscored by a previous cost-effectiveness modelling study that found a risk-stratification approach for surveillance to be more cost-effective than annual or biannual surveillance. [41] Meanwhile, 30% of CRC cases in IBD are missed during surveillance and can therefore be classified as interval carcinomas. [42] Furthermore, half of the CRCs diagnosed in patients with IBD who underwent a colonoscopy in the past five years, can be attributed to a previously missed lesion, despite adequate procedural quality measures. [37]
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC). Current guidelines recommend frequent surveillance colonoscopies for patients with at least left-sided ulcerative colitis, or Crohn's disease involving more than 30% of the colon. Surveillance allows for early detection and treatment of colorectal dysplasia and cancer. The first colonoscopy should be performed 8 to 10 years after onset of disease symptoms. European and British guidelines employ a risk-stratification algorithm that assigns patients to surveillance intervals of one, three or five years, whereas American guidelines recommend to perform surveillance every 1 to 3 years based on the (combined) presence of risk factors. Patients with concomitant primary sclerosing cholangitis are at an additionally increased risk, and should undergo annual surveillance starting immediately after the diagnosis. The current practice of surveillance is based on limited evidence, is resource intensive and cannot preclude the occurrence of interval carcinomas. Fortunately, advances in endoscopic techniques for mucosal visualisation, along with better control of inflammation, have resulted in a declining incidence of CRC in patients with IBD. Furthermore, advanced endoscopic resection techniques can be expected to result in a shift from surgical to endoscopic management of dysplastic lesions. In this review, we provide an up-to-date overview of colitis-associated CRC pathophysiology, epidemiology, surveillance practices, and management of dysplasia.
The Role of Narrowed Spectrum Technologies and Dye-based Endoscopy in Inflammatory Bowel Disease: New Advances and Opportunities
2021, Techniques and Innovations in Gastrointestinal Endoscopy
Endoscopic assessment of inflammation and mucosal healing is an important tool for the appropriate management of patients with inflammatory bowel diseases (IBD). The current definition of mucosal healing using standard white-light endoscopy is being challenged because often histological activity which by itself correlates with clinical outcomes, is being observed. New endoscopic techniques using optical and digital enhancement have highlighted fine details of mucosal and vascular patterns, reflecting better histological changes in the inflammation and healing processes. These technologies can also define colonic lesions in IBD. As the method of choice, recommended by the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC), was dye chromoendoscopy with targeted biopsies, recent studies have demonstrated similar efficacy of high definition endoscopy and virtual chromoendoscopy for dysplasia detection in IBD. Furthermore, these techniques can help characterize endoscopic resectability of lesions, a term the SCENIC consensus has introduced, thereby help in colon preservation in selected cases. Finally, as in other fields in Gastrointestinal endoscopy, neural networks for computer aided diagnosis and endoscopic pattern recognition is being introduced in the field of IBD, and are the new future at the horizon in assessing accurately disease activity and colonic lesions, to support decision making processes. This review will present the use of advanced endoscopic techniques in the assessment and management of IBD.
Occurrence of Colorectal Cancer After a Negative Colonoscopy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
2024, In Vivo

View all citing articles on Scopus

: Conflicts of interest This author discloses the following: Bas Oldenburg is a consultant for AbbVie BV, MSD BV, and Ferring BV. The remaining authors disclose no conflicts.

View full text

Original articleAlimentary tractIncidence of Interval Colorectal Cancer Among Inflammatory Bowel Disease Patients Undergoing Regular Colonoscopic Surveillance

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients

Surveillance Cohort

Discussion

Lancet

Gastroenterology

Gastrointest Endosc Clin N Am

Gastroenterology

Gastroenterology

Gastrointest Endosc

Gastrointest Endosc

Gastroenterology

J Crohns Colitis

Ulcerative colitis and colorectal cancer. A population-based study

N Engl J Med

Original article
Alimentary tract
Incidence of Interval Colorectal Cancer Among Inflammatory Bowel Disease Patients Undergoing Regular Colonoscopic Surveillance