The incidence of inflammatory bowel disease is on the rise, with an estimated prevalence of 25,000 cases in Hungary [1]. Ulcerative colitis (UC) is a chronic inflammatory disease of unclear aetiology involving the entire colon. Treatment is primarily medical, but therapy-resistant or complicated cases require surgical intervention aimed at total resection of the colon and rectum, possibly with reconstruction comprising the creation of a pouch in the terminal ileum. Today, proctocolectomy followed by ileal pouch-anal anastomosis (IPAA) is the accepted surgical procedure [2]. Since inflammation that persists for years or decades may involve the risk of malignant transformation without appropriate treatment and gastroenterological follow-up, regular colonoscopies and follow-up for UC patients are crucial. In 2015, the incidence of UC was 21.7/100,000 individuals in Hungary, with an annual mortality rate of 0.01%–0.023%, colorectal cancer being the leading cause of death [3]. However, the possibility of malignant transformation of a chronic inflammation was suspected by German pathologist Rudolf Wirchow as early as the mid-19th century [4].

There have been reports of UC-associated colorectal cancer since the 1920s [5]. The incidence of inflammatory bowel disease-associated colorectal cancer is very low, contributing to only 1%–2% of all colon tumours; however, it is the cause of death in 15% of the UC patient population [6–8]. Unlike sporadic colon cancer, UC-associated colon cancer develops at a younger age and is caused by a malignantly transformed dysplastic lesion associated with chronic colitis [9]. The extent and duration of UC, the involvement of the terminal ileum, the presence of primary sclerosing cholangitis (PSC), and family history may all affect the risk of occurrence [6, 10–13].

Our study objective was to retrospectively assess the occurrence and surgical treatment of UC-associated colorectal cancer cases in our institute and analyse survival data.

In the Department of Surgery at the University of Szeged, 39 patients (12 females and 27 males) underwent surgery for UC-associated colorectal cancer between 1 January 2005 and 1 January 2025, with an increasing number of cases annually; they correspond to 25% of all patients who received surgery for UC in our institute in the period specified. The ethical permission number is 175/2023-SZTE RKEB. Their mean age was 55 ± 13.4 years (range: 22–84). Clinical characteristics, risk factors, surgical variables, perioperative outcomes, and long-term survival were assessed retrospectively. Survival was analysed using the Kaplan–Meier method and compared between groups with log-rank tests; curves were displayed with confidence bands.

Because median survival could not be estimated in several strata (the survival curve did not drop below 50% within the follow-up), survival was additionally summarised using the restricted mean survival time (RMST) with a standard error (SE). RMST is the average survival time up to the observed follow-up horizon (i.e., the area under the Kaplan–Meier curve) and provides an intuitive, model-free measure that remains informative under censoring.

To account for multiple comparisons, p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR) procedure. Given the exploratory nature of the study and limited sample size, both unadjusted and FDR-adjusted p-values were reported and interpreted to balance type I error control with adequate sensitivity to detect potentially relevant signals.

Multivariable Cox regression was not performed because the number of events was low relative to the number of clinically relevant covariates, resulting in an unfavourable events-to-variable ratio that would likely yield unstable, overfitted adjusted estimates.

Statistical analyses were performed with JASP (version 0.95.2). A two-sided significance level of α = 0.05 was used.

UC-associated colorectal cancer is a highly malignant disease in young patients with a risk of development that gradually increases after 10 years following a UC diagnosis [6, 11, 13]. Carcinogenesis is based on a chronic inflammation-associated progressive dysplastic condition, which differs considerably from the pathophysiology of sporadic colorectal tumours [14].

Between 1 January 2005 and 1 January 2025, a total of 156 patients with UC underwent surgery in our institute, with malignancy confirmed in 25% of them (39 cases) and the number of such cases ever increasing. In view of the risk of malignant transformation of UC, regular colonoscopies and patient follow-up are important. In patients with regular check-ups, Choi et al. detected tumour development at an early stage in 80% of cases [15]. According to the 2017 ECCO (European Crohn’s and Colitis Organisation) guidelines, endoscopy is recommended 8 years after the first symptoms appear [16]. Subsequently, follow-up colonoscopy is recommended annually for high-risk patient populations, whereas low-risk patients require follow-up every 2–3 years; otherwise, follow-up every 5 years is recommended. Based on the ECCO guidelines, among our higher cancer-risk patients, regular surveillance was performed in 1 of 2 PSC cases and in all 3 patients with a positive family history. Among patients with colitis of more than 10 years’ duration, 17 out of 29 participated in regular follow-ups. It is important to note that since thirteen patients did not have regular gastroenterological follow-up visits, regular endoscopies were performed in only 66% of our patients; 66% of the patients had active colitis.

The risk of malignant transformation may be further increased by the occurrence of PSC, which was observed in 2 cases among out-patients in the form of a disseminated, incurable condition and a large liver metastasis [12]. However, a 10-year retrospective Japanese study found no relationship between PSC and cancer risk [17]. Nonetheless, the majority of the literature identifies PSC as a clear risk factor for colorectal cancer in patients with UC [13, 18, 19]. One retrospective study reported a significantly higher risk of colorectal cancer in cases of PSC when associated with IBD. According to the study, the clinical course of this form of PSC also differs from that of isolated PSC [20]. Prior biologic therapy has also been raised as a possible risk factor, but it was not confirmed with the animal experimental model in an Italian study [21]. Six of our patients had received biologic therapy, and the surgical procedure was performed electively with the laparoscopic technique in each case. The extent of UC, the involvement of the terminal ileum, and family history are also possible risk factors [10, 13]. Further, a Dutch survey clearly notes active smoking as a risk factor [22]. Based on data from the literature, prior appendectomy has also been suspected as a risk factor for cancer [23]. In addition, a Chinese summarising study and meta-analysis covering a period of 30 years observed the extent and duration of colitis and geographical factors as independent risk factors. Hungary is among the top countries for incidence of UC-associated colorectal cancer [24]. Anti-inflammatory drugs, especially 5-ASA, play an important role in preventing malignant transformation and in reducing cancer risk [13, 16, 25, 26]. However, the exact mechanism underlying this effect remains unclear, as other anti-inflammatory agents, such as steroids and immunomodulators, do not exhibit a similar effect [27]. 5-ASA is used as first-line therapy for mild to moderate ulcerative colitis. According to the ECCO recommendations, lifelong use may be considered for its chemopreventive effect [28], although its efficacy in combination with other chemopreventive agents is uncertain [16, 28].

During surgical management of UC-associated colorectal cancer, as when surgery is performed for the benign, inflammation “only” type and its complications, removal of the entire target organ, the colon, should be the aim. However, the type and extent of the surgical procedure are determined by the general condition of the patient, the extent of UC, the location of the tumour, the involvement of the sphincter, and the question of oncological treatment. A study from the Far East considers the creation of IPAA and the use of laparoscopy a safe surgical solution for UC-associated colon cancer [29]. Two European studies also referred to IPAA as the gold standard surgical solution [30, 31]. Our study includes 34 elective and 5 emergency surgeries. Among the elective procedures, there were 29 minimally invasive cases and 2 open ones, with conversion being required in 3 cases. Colectomy/proctocolectomy was performed in 21 of our 34 elective cases; of these, IPAA was created in 11 cases. In total, a minimally invasive method was used in 74.3% of the surgeries, and resection was performed in 34 patients (87.1%).

There are 8 cases of rectal cancer among our patients, all in the elective surgery group. Neoadjuvant oncological treatment was possible in 3 cases, and it resulted in 1 confirmed case of complete pathological regression. An Italian working group considers UC-associated rectal tumours a separate entity, emphasising the role of oncological treatment [32].

Lymph node involvement was confirmed in 17 cases (44.5%), whereas 12 patients (30.7%) showed dissemination. During our follow-up, recurrence occurred in 2 cases, that is, in 5.8% of our patients. A Japanese study found young age and stage III to be the main risk factors for recurrence [33].

Results in the literature are divided on UC-associated colorectal cancer survival, but they show a poor prognosis overall [34]. A previous Hungarian epidemiological survey highlighted colorectal cancer among the malignancies of the UC population with unfavourable survival measures, a finding which is consistent with our own experience [3]. The mean survival of 98.6 months observed in our patients was significantly shortened by the following factors: an emergency surgical procedure, smoking, occurrence of PSC, and lack of gastroenterological follow-up.

Several studies found no differences in survival between sporadic and UC-associated cancer groups [34–37]. Other studies, however, attribute a very poor prognosis to UC-associated colorectal cancer [38–40].

The results of our study, although limited by the low number of cases, are consistent with reports that suggest that UC-associated colon tumours represent a group of diseases with a highly aggressive course and early onset. The 25% rate for malignant transformation in our patients is considered very high. It exceeds international results: in two European surveys among patients operated on for UC, colorectal cancer occurred in 12% and 16.9% of cases, respectively [31, 41]. Several of our patients had a disseminated disease at the time of surgery, but the percentage of curative surgeries was also high, thus impacting long-term survival considerably. Our observation is supported by a Hungarian survey that notes unfavourable results for survival [3], which, based on our study, is significantly shortened by PSC, lack of follow-up, smoking, and emergency surgery. Based on our experience, it is especially important for UC patients to receive close gastroenterological follow-ups in specialised centres and undergo regular colonoscopies and for staff to evaluate biopsy samples properly and perform appropriate surgical procedures in due time, preferably proctocolectomy and creation of IPAA with a minimally invasive method. Because of the incidental finding of malignancy and multilocular lesions, central ligations are recommended during routine resections for UC.

European results for survival outcomes in UC-associated malignancies are heterogeneous, with most studies reporting unfavourable outcomes, thus confirmed by our present observations. However, our study is limited by the low number of cases, as well as by the lack of survival data for the tumour-free UC population and for patients with sporadic colorectal carcinoma [31, 41].