Moving from Lymph Node Metastasis In Gastric Cancer to Biological Markers: Reply to Letter

Abstract

Lymph node metastasis (pN category) and tumor depth invasion (pT category) have been the most important prognostic factors for patients with gastric cancer. In the pN category, although several studies [1–7] have clarified the prognostic significance of the metastatic lymph node ratio (MLR) in gastric cancer, it has not been widely used in clinical practice compared with the UICC/AJCC system commonly used in Western countries and the JGCA system commonly used in Japan. The MLR system has the advantage that it is independent of the number of dissected lymph nodes, which may be affected by the surgeon’s attitude toward lymph node dissection. Moreover, it is simple, convenient, and reproducible for predicting the prognosis as well as for treatment planning. Our study also revealed the superiority of the MLR for evaluating lymph node metastasis in patients with gastric cancer compared with the UICC/AJCC and JGCA systems, although the sample size of the study was small (n = 186). Micrometastases or isolated tumor cells in lymph nodes may also be an effective predictive factor for gastric cancer. Nevertheless, patient deaths due to gastric cancer recurrence after curative gastrectomy with D2 lymphadenectomy might be closely related to the large number of lymph node metastases, more advanced N stage, or high MLR rather than micrometastases or isolated tumor cells in lymph nodes. We think that the pN category, especially the MLR, is the key to making decisions regarding adjuvant treatment for locally advanced gastric cancer after a complete surgical resection (R0). Cases with more advanced lymph node metastasis (e.g., MLR [0.2) should be treated with intensive adjuvant chemotherapy [8, 9] rather than with S-1 [10], which is commonly used as adjuvant chemotherapy for stage 2 or 3 locally advanced gastric cancer in Japan. In fact, we select the adjuvant treatment for locally advanced gastric cancer based on the metastatic lymph node status evaluated by the MLR system. In addition to the MLR, micrometastases, and isolated tumor cells in lymph nodes, a biologic marker—human epidermal growth factor receptor 2 (HER2)—has been recently found to be a prognostic factor for gastric cancer. Indeed, molecular targeting therapy using trastuzumab for advanced HER-2-positive gastric cancer has been reported [11]. I believe that we should move forward and develop new biomarkers, target agents, and novel drugs to improve the prognosis of patients with advanced gastric cancer.