A Novel Approach for Gastric Cancer Staging in Elderly Patients Based on the Lymph Node Ratio

Due to improvements in the nutritional status and healthcare support systems, life expectancy has increased in recent years. However, the number of elderly patients with malignant diseases has also increased [1]. In Korea, the prevalence of gastric cancer is high and the number of elderly patients diagnosed with gastric cancer is increasing due to cancer screening through regular endoscopies [2]. The treatment principle in elderly patients is not different from that in non-elderly patients. However, there might be great concerns regarding the treatment approach and the extent of treatment due to the morbidity and fragility in elderly individuals. Therefore, finding an optimal way for the management and evaluation of elderly patients has currently become a major concern and a point of interest.

Since elderly patients are more likely to have underlying diseases and unknown medical histories compared to younger patients, risk factors such as diabetes and hypertension may complicate surgeries in these patients with cancer [3]. Therefore, more delicate preoperative examination and postoperative patient care are necessary. In addition, extensive surgery may damage the fragile tissues of the elderly patients, causing severe complications [4]. Limited lymph node (LN) dissection due to concerns about postoperative morbidity and fragility can underestimate the practical LN status with conventional N staging.

The lymph node ratio (LNR) is the ratio of metastatic LNs to dissected LNs [5, 6]. Several studies have shown that the LNR concept is more sophisticated than N staging for evaluating the prognosis in patients with advanced gastric cancer. In previous studies, the LNR was found to be a useful indicator and an independent negative prognostic factor in patients who had undergone curative gastric resection [6, 7, 8, 9, 10, 11, 12]. Moreover, studies have shown that the LNR is also useful in evaluating the indications for postoperative treatment such as adjuvant chemotherapy and in selecting the regimen [6, 13].

The purpose of the present study was to develop a new N staging system using the LNR to evaluate the usefulness of LNR staging in elderly patients, and to compare it with the current N staging.

In the present study, we classified 605 elderly gastric cancer patients using the newly defined LNR stages and analyzed their OS by stage (Fig. 2). Significant differences in OS were identified among the different N and LNR stages. To eliminate the effects of potential confounding factors that may influence the survival rate, we conducted a multivariate analysis, which showed that the N stage and LNR stage were significant predictors of prognosis. However, the change in the HR between the LNR stages was much greater than that between the respective N stages, indicating that the LNR stage is a more effective indicator of LN status and prognosis in elderly patients than the N stage. To the best of our knowledge, this is the first analysis of LNR staging in elderly patients with gastric cancer who may require limited LN dissection.

TNM staging is the most commonly used staging system for predicting the prognosis of gastric cancer and the most recent version was published in the 8th edition of the AJCC guidelines. The N stage represents the nodal status and the most advanced stage (N3b) requires the evaluation of at least 16 LNs [15]. Since the LNR is not affected by the number of retrieved LNs, it is advantageous when extensive LN dissection is harmful, especially in patients with preoperative morbidity. D2 LN dissection is the standard treatment for advanced gastric cancer. However, we previously reported that D2 or higher level of dissection did not improve survival, but increased the risk of complications in elderly patients [4]. Usually, extensive LN dissection requires a significantly longer operation than limited LN dissection, posing a risk of significantly greater blood loss. In addition, lengthier operations increase the risk of complications resulting from general anesthesia. Therefore, extensive LN dissection is likely to pose a higher risk to patients with cardiovascular or respiratory diseases and to elderly patients who are more vulnerable to postoperative bleeding and complications of anesthesia [4, 16]. Limited LN dissection rather than extensive LN dissection is recommended for such patients. Our LNR staging may be more useful in cases requiring limited LN dissection when compared with traditional TNM staging, which requires at least 16 LNs. The LNR may exhibit a greater positive predictive value in elderly patients who can undergo limited surgery due to their fragility. This may support the official establishment and implementation of the LNR staging concept. Patients with high American Society of Anesthesiologists physical status scores (≥3) should be evaluated using LNR staging. Further studies including larger patient populations who require limited LN dissection may help establish the utility of LNR staging in clinical practice. If LNR staging is observed to be more effective than conventional N staging across all age groups, it may be used as an alternative to N staging.

To date, most of the studies involving the LNR have used a single cut-off value to divide patients into only two LNR groups. However, different studies have suggested different cut-off values and no official numerical standard has been put forth to replace the N stages. For example, various studies have proposed cut-off values of 0.1, 0.25, 0.4, and 0.75 for LNR staging [5, 7, 17]. Such two-stage systems are inappropriate for use in clinical practice. One of the strengths of the present study is LNR grouping and subsequent staging using three specific cut-off values: 0, 0.1, and 0.6. These values are easy to apply in clinical practice, as they follow a structure similar to conventional N staging. We initially selected a cut-off value of 0 and divided all patients into the LNR = 0 and the LNR >0 groups. Subsequently, we created 10 groups using increments of 0.1 and established the cut-off values of 0, 0.1, and 0.6 based on significant changes in the HR. This process resulted in four LNR stages: LNR0, LNR1, LNR2, and LNR3, the same number as that in the N staging system. The LNR staging concept can be applied in clinical practice in a manner similar to N staging while compensating for its deficiencies.

One of the advantages of the present study was the number of patients included in the study. Although we included only elderly gastric cancer patients (aged >75 years), the study population was sufficiently large to conduct a robust analysis. Hence, although our method of calculating the cut-off values was based only on the HRs, our results are expected to be reliable. We recruited a large number of patients from a limited age group and implemented practical and specific standards in a simple way. The results of this study suggest that LNR staging may be an effective new method for evaluating the prognosis in elderly patients with gastric cancer.

This study has several limitations. It was a retrospective single-center study. Therefore, there is a potential for selection bias. We divided the stages based on the HRs from the Cox proportional hazards model and did not employ more precise statistical methods such as a receiver operating characteristic curve. However, we included a relatively large number of patients and generated sufficient data to acquire cut-off values to demarcate the four groups, similar to the current N staging system.

This is the first study to evaluate the usefulness of LNR staging in elderly patients with gastric cancer. Based on the results of this study, we propose a new LNR staging system, which is similar to conventional N staging. We found that LNR staging is more useful than N staging in predicting the prognosis in elderly patients with gastric cancer who may need limited LN dissection. Therefore, LNR staging can be used to complement or replace conventional N staging in elderly patients with gastric cancer.