Colorectal cancer (CRC), with an estimated 1.9 million new cases and 935,000 deaths globally in 2020, stands as the third most prevalent cancer and the second leading cause of cancer-related mortality, contributing to approximately one in 10 cancer cases and deaths (1). Since circa 2010, the incidence of regional-stage and distant-stage disease has increased by about 3% per year in people younger than 50 years and by 2% and 0.5% per year, respectively, in people aged 50–64 years, while rates in people aged 65 years and older have stabilized since about 2015 after a decade of steep decline (2). This trend may necessitate a revision of current screening programs (3).

Endoscopy, particularly colonoscopy, has evolved to be an integral component of the preoperative assessment in patients with colorectal cancer, not just for its diagnostic capabilities but also for its prognostic implications. The occurrence of endoscopic obstruction (eOB) in individuals with colorectal cancer is not uncommon (4), and eOB is defined as the inability of standard colonoscopy to penetrate the tumor, regardless of clinical signs of intestinal obstruction (abdominal distention, peristalsis abdominal pain, nausea, or vomiting) or imaging findings of intestinal obstruction (dilated intestinal loops). Meanwhile, recent studies indicate that eOB is a marker of poor prognosis in patients with stage II colon cancer and stage III rectal cancer following curative surgery (5, 6). Therefore, early identification of eOB is critical for the patient’s treatment. Colorectal obstruction caused by colorectal cancer occurs in 7%–29% of all patients with colorectal cancers (7, 8). Yang et al. indicated that left-side colon cancer was more common than right-side colon cancer in the complete obstructive colorectal cancer compared to the non-obstructive colorectal cancer (9). However, the association between eOB and tumor location has not been investigated. Beyond the influence of tumor location, a distinct variation in tumor size distribution has been noted between eOB and N-eOB. Chalieopanyarwong et al. observed that CRC with N-eOB had a significantly smaller size (4). Smaller tumor size has been reported to be associated with good survival and oncological prognosis in CRC (10). However, several recent studies have reported that tumor size is not associated with survival (11, 12), while others have shown that a smaller size is associated with poorer survival (13, 14). Based on these recent findings, the association between tumor size and oncological prognosis is controversial.

The objectives of this study were to conduct a population-based analysis evaluating the association between primary tumor location and eOB. Additionally, the study aimed to determine the impact of eOB with tumor size ≤ 5 cm on oncological prognosis.

Few studies have focused on identifying the factors associated with the emergence of eOB, as well as conducting analyses to evaluate the prognostic implications of eOB with different tumor sizes. This study demonstrated that the incidence of eOB is predominantly higher in the right-side colon compared to the left-side colon in patients diagnosed with non-elderly colorectal cancer. Furthermore, it was noted that eOB with tumor size ≤ 5 cm was associated with a poor survival compared to N-eOB. Conversely, this correlation was not observed for eOB with tumor size > 5 cm.

Unplanned emergency surgeries for colorectal cancer are typically linked with a heightened risk of surgical complications, as well as increased mortality and morbidity rates in emergency scenarios (17–19). A recent study suggested that in instances of luminal obstruction, which is significant enough to impede the further advancement of a colonoscope, physicians should be prompted to contemplate the necessity of urgent surgical intervention, irrespective of the initial symptoms presented (4). Given the importance of preventive interventions, it is crucial to assess the risk factors associated with the emergence of eOB in patients with colorectal cancer. Previous studies presented inconsistent results regarding the relationship between bowel obstruction development and different tumor location. Theoretically, right-side colon cancers are usually ulcerative, and the stool in these regions tends to have a more liquid consistency. Conversely, left-side colon cancers are more likely to present with bowel obstruction, as proliferative lesions are common in this location and the stool is typically of a semisolid consistency. Xinger Lv et al. (20) and Phillips et al. (21) indicated that the left-side colon was more susceptible to bowel obstruction compared with the right-side colon. However, our results demonstrated an increased susceptibility of the right-side colon to eOB, in comparison with the left-side colon and the rectum. Similarly, Kumar et al. observed analogous finding that relatively younger patients present to health center with obstructive colorectal cancer with anatomical shift to the right-side colon (22). In their study, in 54% cases the lesion was in the proximal colon. It is highly plausible that this outcome is attributable to the screening policies. A study indicated that screening for colorectal cancer is associated with lower disease stage (23). Nevertheless, nearly 90% of colorectal cancer patients are diagnosed following the onset of symptoms, exhibiting more advanced disease stages compared to patients identified through asymptomatic screening (24). Furthermore, when presenting with obstruction symptoms, right-side colon cancers are generally at a more advanced stage of progression compared to left-side colon cancers. Relatedly, this study reveals a strong correlation between a more advanced pT stage and the emergence of eOB, which appears to support the hypothesis that eOB is more common in right-side colon cancers. In addition to the reasons previously mentioned, the inability of the colonoscope to smoothly navigate through the space-occupying lesions in the right-side colon, as compared to those in left-side colon and rectum, may also be attributed to discomfort experienced during the colonoscopy or to technical challenges encountered.

In this study, we observed that eOB with tumor size ≤ 5 cm exhibited a poorer DFS, compared to N-eOB. This relationship was present even when controlling for multiple patient-specific prognostic factors, such as preoperative CA19–9, perineural invasion, pTNM stage. Therefore, to give a potential explanation of our findings, we hypothesized that eOB with tumor size ≤ 5 cm may be a surrogate marker for biological aggressiveness resulting in inferior DFS, which indicated that initial biological heterogeneity of colorectal cancers determined their distinct growth pattern and different invasive and metastatic abilities. In this study, eOB with tumor size ≤ 5 cm was associated with higher pT stage, reflecting a vertical growth pattern. Tumors with a vertical growth pattern may have early acquired high metastatic potential which enable them to breach basal membrane, invading the surrounding tissue and finally disseminating to regional lymph nodes and distant metastasis (25). In contrast, tumors with a horizontal growth pattern reflected by eOB with larger tumors underline a biologically indolent disease and a lower metastatic ability. The fact that clinicians are more likely to treat large tumors more aggressively may also explain our results. Multivisceral resection (MVR) is associated with increased tumor size in locally advanced colorectal cancer (26). In addition, the larger tumor size often leads to more complete lymph node resection and evaluation in colorectal cancer (27). These more aggressive treatments may result in better survival rates. Therefore, in the diagnosis and treatment of colorectal cancer, the evaluation of eOB with smaller tumors should not be overlooked. In addition, preoperative CEA was not an independent prognostic biomarker according to our study. One study has shown that patients with elevated preoperative CEA that normalizes after surgery have a similar outcome to patients with normal preoperative CEA (28). This adequately demonstrates the limitations of preoperative CEA in predicting postoperative recurrence.

This study indeed has several limitations. (1) This study was conducted as a single-center retrospective analysis. Consequently, the number of patients was limited, and the selection process adhered to stringent inclusion and exclusion criteria. This approach may have introduced potential selection bias. (2) The stratification by tumor size and eOB led to relatively small subgroups, which reduced the statistical power to discriminate small differences. (3) Neoadjuvant chemotherapy, radiotherapy and laboratory examinations were not included in the present study. Further investigations of multi-center prospective study should be conducted and more baseline characteristics should be enrolled.

Among non-elderly patients, those with eOB were significantly associated with right-side colon cancer as opposed to left-side colon cancer and rectal cancer. The eOB with tumor size ≤ 5 cm was associated with lower DFS, while this association was not observed for eOB with tumor size > 5 cm. The observed shift in the incidence of eOB towards the right-side colon, coupled with the result that eOB with tumor size ≤ 5 cm may denote a more aggressive form of malignancy, highlights the imperative for comprehensive research.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by The Ethical Review Board of the Longyan First Affiliated Hospital of Fujian Medical University (approval number: LYREC2024-k024-01). The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin because this study utilizes medical records obtained from previous research and meets all of the following conditions: Previous research has obtained written consent from the participants, allowing other research projects to use their medical records or specimens. This research complies with the permission conditions of the original informed consent. The confidentiality of the participants' privacy and identity information is ensured.

NY: Data curation, Methodology, Software, Writing – original draft. SL: Conceptualization, Data curation, Writing – original draft. XW: Writing – review & editing, Conceptualization. GH: Data curation, Methodology, Writing – original draft. RX: Data curation, Writing – original draft. ZQ: Data curation, Writing – original draft. RL: Data curation, Writing – original draft. DX: Conceptualization, Writing – review & editing, Data curation, Methodology.