Does lymph node dissection improve the prognosis of patients with colorectal cancer?

Abstract

The number of lymph nodes (LNs) dissected during surgery has become an interesting topic. Simple intuition always leads us to believe that dissecting more LNs will result in more accurate pathological staging and assurance of surgical quality. However, when the number of LNs dissected reaches a certain threshold, the patient’s prognosis does not continue to improve as the number of dissected nodes increases. Instead, an increase in the number of dissected LNs may be accompanied by a higher incidence of complications. Currently, there are only less than 40% of colorectal cancer patients undergoing adequate LN evaluation. Therefore, obtaining a sufficient number of LNs in clinical practice is extremely challenging. How to further address the insufficiency of LN dissection due to various reasons, which results in concerns of surgeons about patient prognosis, is currently a critical focus.

Key Words: Number of lymph nodes; Colorectal cancer; Overall survival; Tumor node metastasis; T stage

Core Tip: Much as obtaining a sufficient number of lymph nodes (LNs) is extremely important for determining the postoperative pathological stage and postoperative intervention treatment and improving the prognosis of colorectal cancer (CRC) patients, it remains a major challenge in clinical practice. The study by He et al confirmed no correlation between the number of LNs dissected in stage I-II CRC and overall survival, which alleviates the concerns of surgeons about insufficient LN dissection and its impact on patient prognosis. However, due to the limitations of this study, more studies are needed to validate the results.

TO THE EDITOR

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, ranking third in incidence and second in mortality[1]. Currently, radical surgical resection remains the most effective treatment for CRC, with lymph node (LN) dissection being extremely important during the surgery. At least the dissection of 12 LNs is recommended by the National Comprehensive Cancer Network guidelines. To date, various studies have explored the optimal number of LNs to be dissected during radical surgery in CRC patients without distant metastasis to accurately determine postoperative pathological staging, formulate correct treatment plans, and further improve patient prognosis[2,3].

Accurately assessing the presence and number of ln metastases is crucial for predicting the clinical outcomes of patients after radical crc surgery

LN metastasis in CRC is the most significant factor affecting the long-term survival prognosis of patients. Previous studies have reported that there is a positive correlation between the number of LNs retrieved and survival rates in patients with stage II CRC. However, other studies have also shown that the postoperative recurrence rate remains as high as 40%[4-6]. One possible explanation for this finding is the failure to identify positive LNs, leading to understaging (N-stage) and subsequent inaccurate postoperative pathological tumor node metastasis (pTNM) stage. This, in turn, leads to more pTNM stage III patients being classified as pTNM stage II, which could explain the higher postoperative recurrence rates observed among pTNM stage II patients. Additionally, it has been shown[7] that retrieving less than 13 LNs during surgery is closely associated with a 10% false-negative rate for LNs.

The number of LNs dissected during surgery has become an interesting topic. We always intuitively believe that a higher number of dissected LNs will result in more accurate pathological staging and assurance of surgical quality. In the latest issue of the World Journal of Gastrointestinal Surgery, an article titled “Lymph node dissection does not affect the survival of patients with tumor node metastasis stages I and II colorectal cancer” by He et al[8], has piqued our interest. They have conducted a retrospective study on 2850 patients who underwent laparoscopic radical CRC surgery over the past 11 years at their hospital and used a Cox regression predictive model to analyze and determine independent risk factors for overall survival (OS) of CRC patients under different T stages. Their study results indicate that age and tumor size are independent risk factors affecting the OS of CRC patients at T1 stage; at T2 stage, age and total complications are independent risk factors; at T3 stage, only age is an independent risk factor; and at T4 stage, age and body mass index are independent risk factors. Therefore, in stage I-II CRC patients, the number of LNs dissected was not correlated with patient OS. However, accurately assessing the presence and number of LN metastases is crucial for predicting the clinical outcomes of patients after radical CRC surgery. The presence or absence of LN metastasis also largely determines whether adjuvant chemotherapy should be administered postoperatively, which has been clearly shown to be beneficial for the disease-free survival (DFS) and OS of patients with LN metastasis[9,10]. However, in cases where the number of LNs dissected during surgery is too small or there is an insufficient postoperative assessment of metastatic LNs, the risk of understaging increases, leading to premature stage migration, which affects the subsequent treatment and prognosis of the patients. Therefore, the minimum number of LNs required for accurate staging of CRC remains controversial. The current guidelines of the American Joint Committee on Cancer also recommend evaluating 12 or more LNs[11]. Through assessing the relationship between the number of LNs detected and prognosis in 664 stage II CRC patients, Choi et al[12] found that compared with patients with 1-7 LNs, those with 15 LNs had an improved median survival of 11 months for stage I and 54 months for stage II. When the critical number of dissected LNs is 12-23, these patients have a good prognosis, with the number of LNs of 21 associated with the best prognosis. However, when the number of LNs is > 23, no correlation is observed[13]. This suggests that more LNs are not necessarily better for evaluating the optimal prognosis. The reason for this may be that, even if all LNs in postoperative specimens are retrieved using pathological techniques, the number of positive LNs will no longer change with the total number of LNs retrieved. As a result, the pathological staging and subsequent treatment of patients will not be affected, and the patient’s survival may remain unchanged. The study by Yin et al[14] can further explain this phenomenon. They used hematoxylin and eosin staining techniques and retrieved more LNs < 3 mm in postoperative pathological specimens, accounting for 33.3% of the total number of LNs. However, among these LNs smaller than 3 mm, the positive LN rate was only 2.4% of the total number of LNs < 3 mm. This explains why despite an increasing number of LNs being retrieved, the positive LN rate remains relatively stable. This finding is consistent with the belief of other researchers in a “ceiling effect” for the number of positive LNs [15].

Tsai et al[16] have determined the minimum number of LNs to be dissected based on the presence or absence of recurrence. They have found that there are no recurrence cases among patients with T2-4N0M0 stage CRC who dissected 18 or more LNs, suggesting that 18 dissected LNs is the optimal number for these CRC patients. Contrary to the conclusions of He et al[8], Sarli et al[17] have revealed in their study that the 10-year survival rate in stage II CRC patients is significantly dependent on the number of LNs dissected during surgery. A reduced number of dissected LNs is associated with an increased hazard rate (HR) for OS in CRC patients. Compared to cases with more than 19 LNs dissected, cases with less than 10 LNs dissected show an increased OS HR of 1.501, while cases with 10 to 18 LNs dissected show no significant increase in risk (P = 0.725). Therefore, the results of this study confirm that the number of LNs dissected is an independent risk factor for the prognosis of stage II CRC patients. The discrepancies observed between the results of these two studies may be attributable to variations in sample sizes, the inclusion of different disease types, disparities in tumor pathological stages, racial differences, and differing follow-up durations. These factors warrant further in-depth investigation in subsequent research. However, population-based data indicate that only 37% of CRC patients undergo an adequate LN assessment, defined as examining at least 12 LNs[18]. Due to concerns about the common pathological understaging of CRC patients, there have been recommendations to consider adjuvant chemotherapy for CRC patients with fewer LNs examined[19]. Many factors can affect the number of LNs obtained, including tumor location, scope of surgical resection, patient age, and pathological techniques[20].

Conclusion

As mentioned earlier, much as obtaining a sufficient number of LNs is extremely important for accurate postoperative pathological staging, postoperative intervention treatment, and improving the prognosis of CRC patients, but achieving adequate LN acquisition is very challenging in clinical practice. The findings of He et al[8] have clarified that the number of LNs obtained in stage I-II CRC is not correlated with OS, which alleviates surgeons’ concerns about the impact of inadequate LN acquisition on patient prognosis due to various reasons. However, this study is retrospective and lacks random group conditions, making it impossible to rule out the influence of selection bias. Furthermore, the retrospective analysis of the data lacks detailed information on each diagnostic and treatment step in the database, resulting in unclear specific conditions of each case. Moreover, there is a lack of studies examining the relationship between the number of LNs retrieved and DFS in stage I-II CRC patients. Therefore, further research is needed to validate the relationship between the number of LNs retrieved and OS and DFS of stage I-II CRC patients.

ACKNOWLEDGEMENTS

The authors acknowledge and appreciate our colleagues for their valuable suggestions and assistance for this letter to the editor.