The management of right-sided colon cancer, which constitutes 30%–40% of colorectal malignancies, necessitates a precise surgical approach to enhance oncologic outcomes [1]. Right-sided colon cancers, particularly those located in the cecum and ascending colon exhibit distinct clinical, molecular, and histopathologic characteristics compared to left-sided colon cancers [2]. Notably, the lymph node (LN) metastasis pattern in right-sided colon cancer is more complex and divergent from left-sided colon cancer due to its variable vascular anatomy and non-sequential lymphatic spread, adding to the challenges in determining the appropriate surgical strategy [34]. Complete mesocolic excision (CME) accompanied by central vascular ligation has emerged as the standard surgical technique for treating right-sided colon cancer [567]. Nonetheless, executing radical LN dissection remains a technically complex process, and determining the scope of lymphadenectomy for clinical early-stage right colon cancer presents a significant challenge [589].

Wide variation exists in the perspectives of early colon cancer management among different medical professionals. For instance, surgeons might consider colon cancer to be early if it can be treated with less extensive surgery, while medical oncologists may regard it as early if the patients do not require chemotherapy. Conversely, gastroenterologists may define early colon cancer based on the feasibility of endoscopic treatment [10]. Regarding surgical extent, the definition of early colon cancer and its implications for lymphadenectomy approaches need to be clarified and unified across specialties. A critical question arises: If early cancer suggests a less extensive lymphadenectomy than CME, what is the most suitable alternative?

An issue that warrants discussion is the routine adaptation of D3 lymphadenectomy or CME for early colon cancer, and whether such extensive surgical approaches can be justified. By evaluating clinical outcomes associated with these surgical techniques, this study aimed to provide evidence-based recommendations for application of these techniques in the management of clinical early-stage right colon cancer and to explore possible alternatives to CME for less extensive lymphadenectomy.

This study was approved by the Institutional Review Board of our institution (No. CNUHH-2023-081). Informed consent was waived due to the retrospective nature of the study.

We retrospectively reviewed data from patients who underwent curative right hemicolectomy for clinical stage 0 or I right-sided colon cancer at our institution between January 2007 and December 2021. Patients with distant metastases, cT3–4 or cN1–2 on preoperative CT imaging, synchronous colorectal cancer, recurrent colon cancer, fewer than 12 harvested LNs, a histologic type other than adenocarcinoma, or who underwent emergency surgery were excluded.

Preoperative examinations, including colonoscopy, chest and abdominopelvic CT, and laboratory tests with serum CEA, were conducted. For patients with tumor invasion into the submucosal (SM) layer, the degree of tumor invasion was classified as SM1–3 [11]: SM1 (invasion limited to the upper third of the SM layer); SM2 (invasion involving the middle third of the SM layer); SM3 (invasion extending into the lower third of the SM layer). Accurate determination of clinical stage was ensured by thorough preoperative CT scan reviews by 2 independent surgeons and a radiologist.

All included patients underwent CME and D3 LN dissection, adhering to oncologic principles. LN dissection was performed by making an incision along the left border of the superior mesenteric vein (SMV). After exposing the SMV, its feeding vessels were ligated at their origins. If the ileocolic artery passed behind the SMV, it was tied off at the right edge of the SMV [12]. In a right hemicolectomy preserving the middle colic artery (MCA), the middle colic root nodes were dissected while preserving both the root and the left branch of the MCA [13]. In an extended right hemicolectomy, the MCA was ligated at its root, and the middle colic root nodes were dissected along with it. The CME and D3 LN dissections in this study were performed by 6 colorectal surgeons, all of whom were experienced and qualified to perform these procedures in a standardized manner.

Mesenteric tissue from the surgical specimens was manually dissected and examined by an experienced pathologic assistant following standard procedures. Due to the vascular variability of the right-sided colon, this histopathologic examination was performed immediately after extraction of the specimen. LN status was defined according to the distribution of LN metastases (LND). LND was classified based on the Japanese classification of colorectal carcinoma [414]. Patients with metastatic LNs were categorized into 3 categories: LND1 (metastases adjacent to the colon or along the vascular arcades of the marginal arteries); LND2 (metastases along the major vessels, including ileocolic, right colic, and middle colic vessels); and LND3 (metastases around the roots of involved major vessels or along superior mesenteric vessels) [4]. Pathologic staging was determined using the classification system of the American Joint Committee on Cancer Cancer Staging Manual, 8th edition.

When analyzing risk factors for LN metastases extending to LND2–3, we grouped pTis, SM1, and SM2, which had LN metastases confined to LND1, into 1 group based on the depth of tumor invasion. Additionally, patients for whom the tumor depth was not available were also included in this group, as their tumor depth was determined insufficient to differentiate.

The chi-square test and Fisher exact test were performed to analyze categoric variables. Variables that were statistically significant at the P < 0.05 level in the univariate analyses, along with known risk factors for LN metastases, including poor differentiation, lymphovascular invasion, and perineural invasion, were subsequently included in a multivariate logistic regression model. A nomogram was then constructed based on the multivariate logistic regression model, using the rms package. All results were considered significant at values of P < 0.05. Statistical analyses were performed using R statistical software, ver. 4.1.2 (The R Foundation).

We analyzed the incidence and extent of LN metastases in patients with clinical stage 0 or I right colon cancer. The results indicated that there was no LN metastasis in Tis right-sided colon cancer, and for SM1 and SM2, LN metastasis was confined to LND1. In contrast, in tumors classified as SM3 or higher, LN metastasis could extend up to LND3. Our study found that the management of clinical early-stage right colon cancer presents unique challenges due to the complex LN metastasis pattern and the difficulty in diagnosing early colon cancer with abdominal CT scans. Although CME and D3 LN dissection is often recommended for non-metastatic right colon cancer [15], the quality of evidence supporting this recommendation is very low, and no specific guidelines for early-stage right colon cancer have been established, making decisions regarding lymphadenectomy challenging. Additionally, it was difficult to establish the surgical extent based solely on the clinical stage identified through CT imaging. In cases where a pathologic examination is performed before surgery via an endoscopic procedure, the extent of LN dissection may be determined based on the endoscopic results.

In managing early-stage right colon cancer, determining the appropriate surgical extent based on CT imaging posed significant challenges. Previous studies have also documented the difficulties associated with diagnosing early colon cancer using abdominal CT scans [161718]. When analyzing each T stage individually (Tx/Tis, T1, T2, T3, and T4), the accuracy of CT was particularly low [17]. The dependence of CT identification on tumor size may contribute to this limitation, as some locally advanced tumors confirmed by histopathologic examination might be too small for CT detection. For instance, in a study involving 4496 patients, CT demonstrated a sensitivity of 63% and specificity of 80% for predicting Union for International Cancer Control stage I [18]. Additionally, CT misclassified 36% of patients assessed as having locally advanced disease and 58% assessed as stage I. Another retrospective study reported a 46.5% likelihood of clinical T0 and T1 cancer cases progressing to a pathologic stage of T2 or higher, along with a 22.9% likelihood of clinical N0 cases advancing to pathologic N+ status [19]. A national population-based study revealed that for radiologic T1–2 diagnoses, there was a considerable 46% rate of pathologic upstaging to T3 or T4 [20]. As for nodal staging, 33.7% of cases deemed radiologic N0 were later identified as pathologic N+. These findings highlight the challenges faced in using CT scans for early colon cancer diagnosis and the need for more accurate diagnostic tools.

Our study reveals 2 main findings concerning tumor depth and LN metastasis. Firstly, we observed a relationship between tumor depth and the incidence of LN metastasis, consistent with prior research. As tumors invade deeper into the SM layer, the risk of LN metastasis increases. In our study of 348 patients, the incidence of LN metastasis was 3.6% for SM1 tumors, 5.1% for SM2 tumors, and 17.5% for SM3 tumors. These findings are in line with previous studies, such as the one conducted by Ueno et al. [21], which reported 2.6% for SM1, 5.3% for SM2, and 18.0% for SM3. Although there may be slight differences in the reported incidence rates, the overall trend of increased LN metastasis with deeper tumor invasion is consistent across studies [222324].

Secondly, our study explored the relationship between tumor depth and the topographic pattern of LN metastasis using the concept of LND. In our patient cohort, we observed that higher LND categories were more likely to be associated with deeper SM invasion. This observation aligns with the study conducted by Kobayashi et al. [25], which analyzed 487 patients and found that 98.5% of cT1 tumors were classified as paracolic (i.e., LND1), while 95.5% of cT2 tumors also fell within the LND1 category, further reinforcing the association between tumor depth and LND classification. Addressing the limitations of earlier research, our study acknowledged the specific limitations of the Kobayashi study [25] , such as the absence of SM invasion data and the inclusion of left-sided colon cancer and rectal cancer. Nevertheless, their study stands out as a unique investigation in this field, providing valuable insights into the relationship between tumor depth and LND.

A previous study reported no LN metastasis to LND3 in cases of pT1 colon cancer [26]. Additionally, based on results of the Japanese Society for Cancer of the Colon and Rectum colorectal cancer registry from 2000 to 2004, Japanese guidelines suggested that for pT1 cancer there was a 2% LN metastasis to LND2, but no metastasis to LND3, and hence recommended D2 dissection for pT1 cancer [27]. However, our research includes more recent patient data and offers a detailed analysis of SM depth regarding LN metastasis and distribution. We found that for depths greater than or equal to SM3, there was potential for LN metastasis to LND3. Therefore, even if the cancer is pT1, if it is at SM3, consideration of D3 dissection might be necessary. While previous studies indicated increased LN metastasis as SM depth increased, limited data exist on LND relative to SM depth [222324]. Further research on LND based on SM depth is warranted.

Our study adds further novelty by developing a nomogram for predicting LN metastasis to LND2–3. This nomogram incorporates factors such as SM invasion depth and lymphovascular invasion allowing clinicians to better assess the risk of LN metastasis and to personalize treatment strategies accordingly. We tried to identify risk factors for LN metastasis extending beyond LND2, proposing that D3 dissection is essential for such extent of LN metastases. Conversely, in the absence of risk factors, and when LN metastasis is anticipated to reach only as far as LND1, a dissection up to D2 would be sufficient. However, due to the limited number of categorized groups, a multivariate analysis including tumor invasion depth could not be conducted.

By comparing our data with previous studies, we can better understand the extent of cancer spread and optimize treatment strategies, including tailoring lymphadenectomy based on tumor invasion and metastatic risk. We suggest that for tumors with depth less than SM2, a less extensive surgical approach than CME could be considered. This approach might be particularly suitable for patients confirmed for surgery after endoscopic treatment, as the risk of LN metastasis is lower in these cases. It is crucial to identify specific patterns of LN involvement based on tumor depth, as this knowledge can guide surgical and therapeutic decision-making, ultimately leading to improved patient outcomes.

Further, our study emphasizes the need for a standardized definition of early colon cancer across medical specialties. The variability in defining early colon cancer among surgeons, medical oncologists, and gastroenterologists complicates the determination of appropriate treatment strategies. Establishing a unified definition will enable better communication among healthcare professionals and lead to more consistent treatment decisions.

The current study has several limitations. First, it was retrospective in nature, thus we cannot entirely eliminate the possibility of selection bias. Second, the study was conducted at 1 center in the Republic of Korea, primarily considering the characteristics of the Asian population, without accounting for the features of other ethnic groups. Third, the small number of patients with varying depths of SM invasion restricts the comprehensiveness of the multivariate analysis in identifying relative factors necessitating D2 or D3 dissection. Fourth, other known risk factors for LN metastasis, such as tumor budding, were not recorded and therefore could not be included in the analysis.

In conclusion, our study provides valuable insights into the management of clinical early-stage right colon cancer, highlighting the challenges in diagnosing early colon cancer with abdominal CT scans and the relationship between tumor depth and LN metastasis. Further research is needed to establish a standardized definition of early colon cancer and explore alternative lymphadenectomy techniques that may provide optimal oncologic outcomes with less surgical morbidity.