Introduction and current state

Colorectal cancer (CRC) is the second most common cancer and cause of cancer-associated death in Europe [1]. There is a general trend of declining CRC-associated mortality most likely due to increased screening, earlier stage detection, and improved treatment options [2]. However, this trend is not seen in inflammatory bowel disease-related CRC (IBD-CRC), specifically ulcerative colitis (UC) and Crohn’s disease (CD) patients.

The incidence and prevalence of IBD is increasing worldwide, with approximately 2.5–3 million Europeans affected [3]. In the European Union, there are an estimated 176,000 new IBD cases annually (53,000 CD and 123,000 UC) [4]. The prevalence of CD in Europe ranges from 1522 to 21312 cases/100,000 persons, and the prevalence of UC varies from 2422 to 2946 cases/100,000 persons [5]. This incidence and prevalence is associated with an estimated direct healthcare cost of 4.6–5.6 billion Euros/year to care for the IBD population [3].

IBD patients are 2–6 times more likely to develop CRC than the general population [6, 7]. Furthermore, when cancer does develop, IBD-CRC patients are affected at a younger age than sporadic CRC patients. IBD-CRC patients are 7.7 years younger than non-IBD CRC patients at diagnosis, with mean colitis-to-CRC intervals reported between 16 and 21 years [8]. In 2001, Bernstein, et al. reported an increased IBD-CRC incidence rate for both CD (2.64; 95% confidence interval [95% CI] 1.69–4.12) and UC (2.75; 95% CI 1.91–3.97) but an increased risk of rectal carcinoma only in UC (1.90; 95% CI 1.05–3.43) [9]. Other studies supported the overall increased CRC risk in UC, but with decreasing relative risk over time [7, 10, 11]. The risk of CRC associated with CD is more contentious. Studies reported the CRC-relative risk 2.5–4.5-fold higher in CD than in healthy subjects [12, 13]. These values have changed over time, and a CD diagnosis may no longer mean that the risk of CRC significantly increased [14,15,16]. However, there are biases in the assessment of IBD-CRC, including its relatively low prevalence, the aging of the study cohorts, and the clinically heterogeneous nature of IBD, which can effect reported rates [17, 18]. Nevertheless, CRC has a huge impact in this patient population and IBD-CRC is responsible for 10–15% of deaths in IBD patients each year [19].

Risk factors

Several known variables impact the risk of IBD-CRC. Age at diagnosis and disease duration are strong, independent risk factors [7, 20]. In general, CRC risk begins to increase 8–10 years after the diagnosis is made, and increases over time. The incidence rates corresponded to cumulative probabilities for IBD-CRC of 2% by 10 years, 8% by 20 years, and 18% by 30 years [10]. The extent of mucosal inflammation and portion of the bowel affected are other risk factors [12]. Pancolitis patients are at higher risk, with prevalence of 5.7% [10]. Patients with left-sided UC are also at higher risk for IBD-CRC; however, patients with ulcerative proctitis have a CRC risk similar to that of the general population [21]. In CD, the relative risk of IBD-CRC is highest in patients with colonic disease and lowest in isolated ileal disease [12, 13, 22]. CD patients with penetrating disease and who have had immunosuppressive therapy are also at significantly higher risk of IBD-CRC [23]. The presence of UC and concomitant primary sclerosing cholangitis (PSC) is another risk. A study from the Swedish Cancer Registry found that patients with an intact colon when diagnosed with PSC had a cumulative CRC risk of 16% after 10 years, while those with UC prior to diagnosis of PSC had a cumulative risk of 25% (24).

Geography plays a role in IBD-CRC development. The risk is higher in North America and the UK than in Scandinavian countries with no evidence of temporal impact [12]. In the US and UK, the annual risk of IBD-CRC is 4–5 cases/1000 person-years, whilst in Scandinavian and other countries it is 2 cases/1000 person-years [6]. The reason for geographic heterogeneity is multifactorial, including genetics, diet, chemoprevention, and differences in colonoscopic surveillance [6]. As with sporadic CRC, family history is associated with increased risk. IBD patients with CRC in a first-degree relative have twice the risk of developing CRC than those who do not [24]; patients with a first-degree relative diagnosed with CRC before 50 have a ninefold higher relative risk [25]. Finally, a personal history of CRC and previous or synchronous colorectal adenomas are risk factors for IBD-CRC. The Gastrointestinal Oncology Group of the Spanish Gastroenterological Association reported that patients with a personal history of CRC [odds ratio (OR), 5.58, 95% CI 1.01–31.01], and presence of previous or synchronous adenomas (OR, 1.77; 95% CI 1.21–3.17) have a significantly increased risk.

The molecular and bacterial basis for IBD-CRC

Molecular alterations that occur in sporadic CRC, such as chromosomal instability, microsatellite instability (MSI) and hypermethylation, play a role in IBD-CRC, but the order and frequency of these mutations, and the fact that they often occur before definite histologically defined dysplasia, differentiates IBD-CRC from sporadic CRC [26] (Fig. 1). The initiation and development of IBD-CRC is linked to inflammation, and follows a sequence of genetic alterations following an “inflammation-dysplasia-carcinoma” sequence, not the “adenoma-sequence” classically described in sporadic CRC [27, 28]. The relationship between chronic inflammation and some molecular mediators that contribute to IBD-CRC are well established. Models highlight the role of toll-like receptors (TLR) and tumor necrosis factor-α (TNF-α) in the activation of nuclear factor κB (NFκB)—a master regulator of inflammation, which then induces transcription of tumorigenesis genes, including COX-2 [29,30,31]. The inflammation induces apoptosis of intestinal epithelial cells via tumor suppressor p53 pathways; defective signaling via p53 may be an early event in the progression of dysplasia to cancer [32]. The p53 mutations occur earlier in IBD-CRC than sporadic CRC. These p53 mutations are also often in grossly normal nondysplastic mucosa, a contrast to sporadic CRC [6]. The development of a nonfunctional adenomatous polyposis coli (APC) gatekeeper gene occurs later in IBD-CRC, just prior to carcinoma; this APC loss of function can occur because of chromosomal instability or MSI abnormalities, presenting in either polypoid or flat lesions [6]. IBD patients tend to have excessive inflammatory cell infiltration and expression of several inflammatory genes; this mucosal inflammation promotes cellular proliferation and ultimately CRC development [33]. With their increased presence in IBD-CRC compared to IBD without dysplasia, specific genetic mutations in KRAS and p53 could serve as biomarkers [34].

Fig. 1
figure 1

Pathways to progression to colorectal cancer in sporadic and inflammatory bowel disease associated colorectal cancer

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The dysbiosis of gut microbiota appears to have a role in IBD-CRC development [35, 36]. E. coli—a major contributor to the induction of chronic inflammation during IBD and convertor of IBD into CRC—is dramatically increased in IBD. The lipopolysaccharides of the gram-negative bacteria increase expression of TLR4, a common event during IBD-CRC tumorigenesis [37]. E. coli also activates NF-kB expression, which plays a role in inducing inflammation and CRC development. Colibactin­equipped E. coli, an aggressive adherent invasive E. coli pathovar, are more prevalent in the colonic mucosa in CD and, to a lesser extent, UC patients [38]. Other organisms overrepresented in the tumor microenvironment may act as pro-inflammatory factors, contributing to IBD-CRC, including Streptococcus bovis and Fusobacterium nucleatum [39]. Understanding of the exact role of the microbiota dysbiotic component is continually evolving, and it will be exciting to search for therapeutic targets.

Chemoprophylaxis

Several agents have been evaluated for chemoprophylaxis, with varying results. A systematic review and meta-analysis in average and high-risk CRC patients evaluated potential benefits of several prophylactic agents; IBD patients were not specifically evaluated, but the outcome can be applied in general [40]. For patients with adenomas or CRC history, there was a significant 21% reduction in adenoma recurrence and a 26% reduction in CRC incidence. In individuals with a history of adenomas, calcium (1200–2000 mg/day) demonstrated a significant 18% reduction in the risk of adenoma recurrence. There was no significant effect with folic acid or antioxidants (vitamins A, C and E, beta carotene or selenium) on adenoma recurrence or incidence. Non-steroidal anti-inflammatory agents, such as Celecoxib (400 mg/day), had a significant 34% reduction in adenoma recurrence and a 55% reduction in advanced adenoma incidence. In CRC survivors, nonsteroidal anti-inflammatory drugs (NSAIDS) are associated with a threefold decreased risk of recurrence and sevenfold decreased risk of death [41].

IBD is a non-modifiable risk factor for CRC; however, there is a role for chemoprophylaxis with pharmacological therapy to reduce the inflammation and causative organisms that increase the risk of CRC [42]. Although it is accepted that chronic inflammation promotes colon cancer and chronic inflammation is the main cause of IBD-CRC, the mechanisms involved are not clear [43]. Suppressing inflammation should lower the risk for IBD-CRC, but studies have not established that the anti-inflammatory agents most commonly used to treat IBD have chemopreventive effects against cancer. Effective anti-inflammatory chemoprophylactic agents are Sulfasalazine and the 5-aminosalicylic acid (5-ASA) agents. Treatment with Sulfasalazine lasting at least 3 months was associated with a significant protective effect independent of disease activity [44]. A recent meta-analysis supported the chemopreventive effect of 5-aminosalicylic acid (5-ASA) agents in dosage ≥ 1.2 g/day in patients with IBD, with a significant additional effect in UC. The agents were effective only against CRC, not dysplasia [45]. Other work has shown mesalamine is associated with risk reduction in the same dosage [46]. Anti-TNF agents induce and maintain mucosal healing in moderate-to-severe IBD and, as a result, likely provide chemopreventative benefits by reducing long-standing chronic inflammation [47]. TNF-alpha has been reported to promote inflammation and IBD-CRC by promoting deoxynucleic acid (DNA) damage, stimulating angiogenesis, and inducing expression of COX-2, which also induces angiogenesis to promote tumor growth. In murine models, TNF-α expression was associated with the development of colonic tumors, while TNF-R blockade reduced inflammation and tumor development [48]; the effect was specifically seen with mice given the anti-TNF agents infliximab and etanercept [48, 49]. Although early investigations into the molecular mechanisms of TNF-α in IBD have suggested that TNF blockers may have a direct antineoplastic role, to date studies in humans have not established that these agents prevent colon neoplasia [47].

An emerging prophylactic agent for prevention of carcinogenesis is probiotic bacteria. Mouse models of CRC have shown that producing conjugated linoleic acid activates PPARγ, which inhibits COX-2 and induces apoptosis [50]. Further study is needed to validate this in human IBD-CRC.

Screening and surveillance guidelines

The aim of surveillance is to detect early dysplasia, and colonoscopy remains the gold standard in diagnosing intraepithelial neoplasia, dysplasia, or cancer in IBD [51]. Screening and surveillance is key to early detection, treatment, and prevention of CRC, but no randomized controlled studies have shown that surveillance colonoscopy in IBD patients reduces the risk of CRC. While the association between IBD and CRC is well established, there are still concerns regarding timely diagnosis and treatment of early neoplastic lesions. Dysplastic lesions in IBD may occur as flat or raised mucosal lesions, and are differentiated by the terms dysplasia-associated lesion or mass (DALM)-macroscopically flat or raised lesions without proper delineation to the surrounding mucosa- and adenoma-like mass (ALM)-sporadic adenomas that are similar to those observed in non-IBD patients (Fig. 2; Table 1). IBD-CRC does not follow the classic adenoma-sequence; the progression to dysplasia is believed to be more rapid than the progression of adenomas to CRC in the non-IBD population [21].

Fig. 2
figure 2

Dysplasia-associated lesion or mass (DALM), adenomatous lesions, and ALM comparison. a Endoscopic view of a DALM under white light; b endoscopic view of a DALM with chromoendoscopy; c endoscopic view of an adenoma; d histology of an adenoma; e endoscopic view of an adenoma-like mass (ALM); f histology of an ALM

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Table 1 Dysplastic lesions in inflammatory bowel disease
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Guidelines from the European Crohn’s and Colitis Organization (ECCO), the American Gastroenterological Association (AGA), the British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) agree that IBD patients are “high risk” CRC, and surveillance colonoscopies should be started 8 years after the onset of pancolitis or 12–15 years after onset of left-sided and CD colitis, to assess disease extent and other endoscopic risk factors. However, there are discrepancies across guideline recommendations regarding the time interval between routine studies [52,53,54]. Colonoscopy surveillance is recommended to reassess disease extent every 1–2 years with biopsies for dysplasia [53, 54]. During surveillance, 2–4 random biopsies should be taken every 10 cm along the entire colon, with additional samples in suspicious areas, and 4-quadrant biopsy every 5 cm in the lower sigmoid and rectum. To aid detection, chromoendoscopy or pancolonic dye spraying with targeted biopsy of abnormal areas is recommended. If a dysplastic polyp is detected within an area of inflammation and can be removed in its entirety, colectomy is not necessary. Post colectomy, yearly flexible sigmoidoscopy of pouch/rectal mucosa in patients is recommended in higher risk patients-(previous dysplasia or CRC at the time of pouch surgery, primary sclerosing cholangitis, mucosa exhibiting atrophy, or severe pouch inflammation). Lower risk post-colectomy patients can consider 5-yearly flexible sigmoidoscopy of the pouch/rectal mucosa if none of the aforementioned risk factors are present, taking four proximal and four distal pouch biopsies [55].

For the first time, the BSG has recommended the use of high-definition endoscopy chromoendoscopy or pancolonic dye spraying with targeted biopsy of abnormal areas [55]. This technique involves spraying a dye, such as indigo carmine or methylene blue, onto the mucosa to enhance visualization of subtle mucosal changes associated with dysplasia or neoplasia. With these tools, dysplasia, previously thought to be ‘invisible’ to the endoscopist, is now considered to be ‘visible’ [56]. This has implications for changing the paradigm of treating dysplastic lesions, where endoscopic resection can be considered, rather than radical surgery. Further studies are needed to determine its efficacy in this high-risk patient population, as well as if the additional training required offers a cost effective solution. Dye-based and magnification chromoendoscopy improve detection of dysplasia, and evaluation of inflammatory activity and extension of UC (Fig. 3). Chromoendoscopy has proved highly effective and several guidelines suggest its use with a target biopsy [19]. Chromoendoscopy with confocal laser endomicroscopy (CLE) is reported to detect 4.75-times more neoplasms than conventional colonoscopy, while requiring 50% fewer biopsy specimens; it is not a technology for lesion detection alone, though [57]. This combination is most useful to identify areas of suspicion in IBD surveillance. However cost, availability, and experience are still an issue [58]. Dye-less chromoendoscopy modalities, including narrow band imaging, iScan, and autofluorescence imaging, can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies, but the evidence to recommend routine use is lacking [59].

Fig. 3
figure 3

Ulcerative colitis colonoscopic view with white light and blue chromoemdoscopy dye

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Whilst the current surveillance protocol is recommended for IBD patients, no randomized studies demonstrate a risk reduction in CRC development or mortality due to surveillance colonoscopy, but indirect evidence suggests surveillance reduces the risk of death [60, 61]. There is evidence that cancer can generally be detected at an earlier stage with surveillance colonoscopy and that these patients have a better prognosis. Lutgens et al. found the 5-year survival rate after an IBD-CRC diagnosis was 100% in patients undergoing standard surveillance, compared to 74% in those not participating in surveillance, and more tumors were found at an early stage in the surveillance group [62]. A recent Cochrane review affirmed that endoscopic surveillance prolongs life by allowing earlier detection of CRC and dysplastic pre-cursor lesions in IBD [63]. The pooled analysis found the surveillance group had a significantly lower rate of CRC detection (1.83% vs. 3.17%, OR 0.58, 95% CI 0.42–0.80; p = 0.0009), earlier stage CRC detection (16% vs. 8%, OR 5.40, 95% CI 1.51–19.30; p = 0.009), and a lower mortality (8% vs. 22%, OR 0.36, 95% CI 0.19–0.69, p = 0.002), respectively [63].

Close clinical follow-up needs to be performed with IBD patients in addition to surveillance colonoscopy for cancer prevention. Issues of compliance with biopsy protocols and undersampling have been reported. In the UK: more than 50% of the gastroenterologists survey obtained fewer than ten colonic mucosal biopsies per examination [64]. In addition, while current guidelines recommend increased surveillance for CRC in this population, adherence remains poor and timing may not be adequate for detection. Much endoscopic surveillance is performed without following internationally recommended guidelines, rendering screening in this population ineffective [65, 66]. A University of Minnesota study reported that almost 50% of their IBD-CRC patients had their cancer diagnosed because increased colitis symptoms led to colonoscopic examination outside of surveillance, and 18% of patients developed cancer with less than an 8-year history of IBD [67]. Another study from the Cancer Registry of Norway reported 21% of CRC in their registry study developed before 10 years since IBD diagnosis, and therefore, before the usual recommended time for starting colonoscopic screening [68]. By relying solely on surveillance guidelines, these cancers could have been missed. Thus, further study should be focused on reassessing and increasing adherence to appropriate guidelines.

Surgical indications and treatment course

Recommendations for surgery are guided by screening and surveillance findings. High-grade dysplasia (HGD), multifocal dysplasia, and invasive carcinoma are an absolute indication for surgery. DALM harbors a high risk of progression to CRC, and is also a colectomy indication. There is over a 50% risk of developing cancer within 5 years of the diagnosis of dysplasia, and patients with DALM have a 20–30% risk of harboring an unrecognized synchronous or metachronous CRC [69,70,71]. Therefore, DALM patients are recommended to have prophylactic proctocolectomy with ileoanal pouch. Newer endoscopic excision techniques, such as en-bloc resection of the lesion with Endoscopic Submucosal Dissection or Endoscopic Mucosal Resection, have been described for resection of DALM and ALM when paired with chromoendoscopy and close surveillance. However, there is no long-term follow-up of outcomes, or controlled comparative studies of endoscopic resection vs. surgical resection, and so resection remains the best practice for DALM. In contrast, ALM patients can be treated with standard polypectomy and endoscopic surveillance with little risk of subsequent malignancy [72, 73]. The need for complete excision in both lesions is stressed, as a high proportion of unresectable lesions harbor cancer [74] (Fig. 4).

Fig. 4
figure 4

Rectal moderately differentiated adenocarcinoma in a Crohn’s disease patient. Gross specimen, moderate, and high power histopathology views

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There is debate on the need for resection after low-grade dysplasia (LGD) is discovered. Both HGD and LGD are risk factors for IBD-CRC, and the likelihood of finding synchronous cancer at colectomy is 42% with HGD and 19% with LGD [52]. The variability in the risk of progression from LGD to HGD or cancer—is 0–50%—leading to controversy about management [75, 76]. Ullman et al. reported a 53% 5-year progression rate to HGD or CRC in UC patients with LGD discovered on surveillance colonoscopy [69]. Connell et al. found similar 5-year progression rates of 54% in long-term surveillance [75]. While it has been proven that LGD can develop into DALM, HGD, and invasive cancer, the time to progression is unknown [76]. Thus, consideration of colectomy is valid with LGD. Wide variations in the perceptions and management of LGD in IBD were seen in a survey of British Society of Gastroenterology members [77]. Seventy percent of respondents considered LGD premalignant, but only 13% offered routine colectomy, compared with 84% for HGD. Eighty-five percent considered LGD with DALM high-risk for concurrent CRC, but only 53% offered total colectomy. Patients were more likely to be treated with colectomy for flat HGD (77%) and HGD in the presence of DALM (86%). Thus, there is a need for more research and consensus on LGD surgical recommendations.

In addition, any patient unable or unwilling to have routine surveillance endoscopy should have surgery discussed to circumvent the risk of IBD-CRC. When the decision is made to have surgery, a treatment course decided by the multidisciplinary team, including the surgeon, gastroenterologist, pathologist, oncologist, and the patient, is needed to optimize outcomes [78]. The goal of surgery in IBD-CRC is to remove all disease and tissue at risk with a complete oncological resection while preserving quality of life. The specific surgical plan varies depending on the diagnosis of UC or CD, the lesion location, the patient’s comorbidities, and personal wishes. IBD-CRC has greater propensity to develop in the proximal colon than sporadic CRC, and is significantly less likely to be located in the rectum compared to sporadic CRC [79]. The stage of cancer distribution is similar for IBD-CRC and sporadic CRC patients, but IBD-CRC tumors are often mucinous, and there is a higher frequency of multiple, synchronous tumors (OR 4.403, 95% CI 2.32–8.36; p < 0.001) and poor differentiation (OR 1.59–1.86, 95% CI 1.26–2.47; p < 0.001) [6, 67, 79,80,81]. Considering the rates of synchronous dysplasia and lesions, under ideal conditions, the surgical procedure of choice in IBD-CRC—both UC and CD—is a total proctocolectomy (TPC) with ileal-pouch anal anastomosis (IPAA) [82]. These recommendations are consistent with population studies that demonstrate IBD-CRC patients—both UC and CD—were more likely to have total colectomy or panproctocolectomy than partial colectomy compared to non-IBD CRC patients [83]. In CD, segmental resection was formerly recommended to spare bowel and prevent Crohn’s disease of the pouch [84]. However, the diagnosis of adenocarcinoma is often not known at the time of resection, and a segmental resection would not guarantee appropriate oncological resection [78]. Furthermore, neoplasia in CD behaves similarly to UC, supporting a more extensive UC-like surgical approach of TPC with end ileostomy, instead of a segmental resection, as the optimal course [85]. An IPAA is also an option in CD. IPAA procedures were historically discouraged in patients with known CD due to high rates of complications and subsequent pouch excision [86, 87]. However, there has been something of a change in the management paradigm. While reported, CD of the pouch remains poorly defined and the diagnosis is often made on a non-specific clinical picture; actual pouch loss rates are low and functional results are favorable [88,89,90]. Thus, IPAA can be recommended in select cases of CD as an alternative to total protocolectomy with definitive end-ileostomy, with the patient well informed of the risks, failure rates, and functional results [87, 91]. Under less optimal conditions, including patient comorbidities, function, and personal preferences, lesser procedures may be made on an individual basis. These procedures for UC include a TPC with permanent ileostomy, subtotal colectomy with ileorectal anastomosis (IRA), segmental resection, and palliative procedures such as diverting colostomy or ileostomy (Fig. 5). For a total abdominal colectomy with a stapled anastomosis, there are a few centimeters of colonic mucosa (1–2 cm) are left in situ below anastomosis, with a risk of malignant degeneration. The hand-sewn IPAA with mucosectomy reduces the risk of retained colonic mucosa below the anastomosis, but does not allow complete removal of columnar epithelium, which can progress to a malignant state [92]. This highlights the need for continued surveillance after surgery.

Fig. 5
figure 5

Single incision laparoscopic total abdominal colectomy with end ileostomy creation, as part of a staged total proctocolectomy procedure

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Postoperative course and prognosis

Postoperatively, IBD adversely impacts outcomes. A review of the National Inpatient Sample and Nationwide Readmissions Database showed IBD-CRC patients had longer length of stay, greater likelihood of postoperative complications, including wound infection and deep vein thrombosis, and were more likely to be readmitted within 30 days than sporadic CRC patients [83]. CD patients specifically were more likely to develop postoperative hemorrhage, hematoma or seroma, wound dehiscence, and poor wound healing [83].

Given the tumorigenetic and histomorphological differences between IBD-CRC and sporadic CRC, different treatment responses could be present. The current data supports the same indications for adjuvant chemotherapy. A morphologic similarity between IBD-CRC and microsatellite instability high (MSI-H) CRC, with less response and higher risk of intestinal toxicity from fluorouracil-based chemotherapy was previously reported [93, 94]. However, the largest study to date comparing oncologic outcomes in IBD-CRC to sporadic CRCs found no significant differences, and supports fluorouracil-based chemotherapy in IBD-CRC [95]. Patients with histologically active IBD also did not require chemotherapy alterations compared to inactive IBD patients [96]. Further prospective studies are needed to guide therapeutic decisions.

Long-term, IBD-CRC has higher recurrence and higher mortality rates than sporadic CRC [67, 80, 97]. A matched analysis reported local recurrence was three times higher (p = 0.004) and 5-year survival significantly lower in IBD-CRC than sporadic CRC (49% vs. 67%, p = 0.03) [97]. A meta-analysis of 3472 patients indicated IBD-CRC patients had shorter survival than sporadic CRC patients (HR 1.24, 95% CI 1.19–1.29) [80]. In a recent case-matched study IBD-CRC patients had a significantly shorter median survival than sporadic CRC (68.2 vs. 204.3 months, p = 0.01); Stage 3 IBD-CRC patients specifically showed significantly decreased survival (23.0 vs. 133.9 months, p = 0.008). On multivariate analysis, after adjusting for N and M stage, IBD was associated with an increased risk of death compared to sporadic CRC (HR 2.011, 95% CI 1.24–3.23, p = 0.004) [98]. Patients with stage IV IBD-CRC also had shorter survival than patients without IBD [96]. Thus, intensive surveillance and early treatment are essential [99]. More robust studies on long-term outcomes for IBD-CRC are needed. Recently, an international cross-disciplinary working group addressed this issue, and proposed a standardized set of patient-centered outcome measures for IBD, including domains of survival, CRC, and disease control [100]. This international template could facilitate better outcomes data in this population going forward.

There is little data on postoperative CD treatment after surgery for IBD-CRC. There is also no compelling evidence that anti-TNF therapy plays a role in solid tumor development. All IBD-CRC patients should receive multidisciplinary management, with collaboration between gastroenterologists and oncologists, and must be based on the individual case, considering IBD activity, concomitant therapy, patient age, and the cancer type and stage [101]. 5-ASA agents and non-systemic steroids should be first line; thiopurines, calcineurin inhibitors, and anti-TNF agents should be stopped at least until cancer therapy is completed [101]. Preliminary data demonstrate no obvious risk of developing a new or recurrent cancer while being treated with anti-TNF therapy. Further research is needed on the topic for definitive recommendations.

Conclusions

The risk of developing CRC is increased in IBD, and affected patients have a worse outcome than patients with sporadic CRC. The increased CRC risk in IBD is thought to be due to chronic inflammatory state, with new theories emerging about additional risk factors. Recognizing these factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing IBD-CRC. Several surveillance strategies are recommended to identify these lesions, and new endoscopic technology is emerging to identify the colitis-associated neoplasms more precisely than random biopsies. When dysplasia is discovered, surgery remains the most conservative option, with further evidence needed on the outcomes with endoscopic resection. After resection, evidence-based guidelines advise surveillance to manage the risk of recurrent dysplasia and CRC. Further study is needed on adjuvant treatment for CRC and CD treatment after surgery.