Prognostic factors and recurrence pattern in node-negative advanced gastric cancer

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Abstract

Aims

Despite better overall survival in node-negative advanced gastric cancer (AGC), a significant proportion of patients develop recurrence and they may benefit from adjuvant therapy. The aim of this study was to evaluate the prognostic factors and recurrence pattern of node-negative AGC.

Methods

A total of 424 patients who underwent curative gastrectomy with extended lymphadenectomy for node-negative AGC between 2003 and 2005 were retrospectively reviewed. Patients with tumor involvement of adjacent organs (T4b), gastric cancer recurrence, tumor in the remnant stomach, less than 15 harvested lymph nodes, and those who received neoadjuvant chemotherapy were excluded.

Results

Invasion to deeper layers, undifferentiated histology, signet ring cell type compared with tubular adenocarcinoma, and tumor size larger than 6.3 cm correlated with poorer prognosis in univariate analysis. In multivariate one, however, only differentiation and depth of invasion, especially the presence of serosa involvement were significant. The 5-year survival rates of the four groups classified by differentiation and depth of invasion [T2/3 (differentiated type), T2/3 (undifferentiated type), T4a (differentiated type), and T4a (undifferentiated type)] were 98%, 92%, 80%, and 72%, respectively (P < 0.01). In terms of recurrence pattern, Lauren's type and depth of invasion were significant. Recurrence with peritoneal seeding was associated with the diffuse type and invasion into the subserosa or serosa, while hematogenous metastasis was related to the intestinal type and invasion to the proper muscle or subserosa layer.

Conclusions

Differentiation and serosa involvement should be considered to stratify patients with node-negative AGC for adjuvant treatment.

Introduction

Nodal metastasis is the most important prognostic factor for survival after curative resection in gastric adenocarcinoma.1, 2 Importantly, many patients have node-negative disease on their pathologic examination. Although node-negative advanced gastric cancer (AGC) shows a better overall survival than node-positive AGC, a significant number of patients still develop recurrence. Patients without node metastasis are theoretically free of locoregional micrometastasis and can potentially benefit from adjuvant therapy.

Several reports demonstrate that the depth of invasion is an independent prognostic indicator in node-negative gastric cancer including early gastric cancer (EGC).3, 4, 5 However, there is still controversy on the prognostic significance of other factors, including patient age, tumor size, histology, differentiation, and the presence of lymphovascular invasion. Moreover, most studies include a significant proportion of patients with EGC, which has a very low risk of recurrence,3, 4, 5, 6, 7 as well as patients with understaged disease due to limited lymphadenectomy and the subsequent small number of retrieved lymph nodes on pathology.4, 5, 8, 9

In this study, by only investigating patients with node-negative AGC, we aimed to evaluate the prognostic factors and their relation to survival. In addition, we analyzed the pattern and indicators of recurrence.

Section snippets

Patient population

Patients who underwent curative gastrectomy with extended lymphadenectomy (R0) for node-negative AGC at the Asan Medical Centre from 2003 to 2005 were identified. Among them, patients with pathologically confirmed tumor involvement of adjacent organs (T4b), recurred gastric cancer, tumor in the remnant stomach, <15 harvested lymph nodes, and those who received neoadjuvant chemotherapy were excluded.

Data collection

The medical records of the resulting 424 patients were retrospectively analyzed to determine

Clinicopathologic characteristics

The median age at operation was 58 and the ratio of men to women was 2. The median tumor size and number of harvested lymph nodes were 5 cm and 27, respectively. Most patients had malignant lesions on the lower third of the stomach and received distal gastrectomy. In addition, most tumors were Borrmann type 3 on gross appearance, had undifferentiated histology, and involved the proper muscle or subserosal layer (Table 1).

Recurrence and survival

At the time of analysis, 40 patients had recurrence, of which 25 had

Importance of the study

Previously, several studies investigated the prognostic factors for node-negative gastric adenocarcinoma with R0 resection. In contrast to previous studies, we excluded patients with node-negative EGC to lessen their confounding effect and patients with less than 15 harvested lymph nodes to eliminate possible understaging. In addition, to the best of our knowledge, our study is the largest scaled one assessing prognostic factors in node-negative AGC.

In other studies, the 5-year survival rate in

Conclusion

In conclusion, serosal invasion and undifferentiated histology are two predictors of poor prognosis in node-negative AGC patients. Moreover, Lauren's type and depth of invasion may be helpful to predict the recurrence pattern of node-negative AGC. Such parameters should be considered to stratify patients for adjuvant treatment. Further studies are needed to confirm that adjuvant therapy can improve survival in such patients.

Conflict of interest statement

The authors have no conflicts of interest or financial support to declare.

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