The Impact of Tumor Size on the Prognosis of Gastric Cancer: Experiences from a European Study Group

Research Article

J Surg. 2016; 3(1): 1082.

The Impact of Tumor Size on the Prognosis of Gastric Cancer: Experiences from a European Study Group

Dittmar Y*, Ardelt M, Scheuerlein H, Rauchfuss F, Dondorf F and Settmacher U

Department of General, University Hospital of Jena, Germany

*Corresponding author: Dittmar Y, Department of General, University Hospital of Jena, Helios-Klinikum Meiningen GmbH, Visceral and Vascular Surgery, Bergstrasse 3, 98617 Meiningen, Germany

Received: February 10, 2016; Accepted: April 07, 2016; Published: April 12, 2016

Abstract

Background: To investigate the impact of tumor size as a prognostic marker in the clinical course of resected gastric cancer on a German study group.

Methods: Based on a prospectively maintained data base, we included 573 cases of resected gastric cancer. Tumor size was measured postoperatively on the pathological specimen by the pathologist. The optimal cut-off point for tumor size was estimated by using the Cox regression model. We performed a tumorsize stratified analysis for several clinical and pathohistological factors in terms of their frequency and size-related impact on survival. The influence of tumor size on the pattern of tumor recurrence was analyzed.

Results: We found longer overall 5-year survival for patients with smaller tumors (69.5% and 36.8%, respectively, p<0.0001). Tumor size was an independent prognostic factor (p=0.042). Tumor size was a significant prognostic factor in curatively resected patients (R0), in both diffuse and intestinal type gastric cancer according to the Lauren classification, in the T2 category, in both well/moderate and poor/un- differentiated tumors, in both node-positive and node-negative categories, in cases with and without lymphangiosis, venous infiltration, cardia tumor location as well as tubular pathohistological growth pattern. Tumor recurrence was less frequent (28 vs. 39%, respectively, p=0.021) and at a later interval in smaller tumors (19 vs. 13 months, respectively, p<0.0001). Lung metastases were observed significantly more frequently in the subgroup of larger tumors.

Conclusion: Tumor size is a strong prognostic factor. In the development of a more individually designed cancer treatment tumor size might be a useful marker.

Keywords: Gastric cancer; Survival; Outcome; Tumor size; Prognostic factors

Introduction

Gastric cancer is known to be the second most frequent reason for tumor-related death worldwide [1]. With a global incidence of 952.000 new cases annually, gastric cancer is now the 5th most frequent malignancy [2].

The late onset of symptoms usually in an advanced tumor stage as well as the lack of eligible screening procedures for gastric cancer cases without symptoms both lead to the sustained poor prognosis [3]. The biology of gastric cancer implicates a strong association between tumor stage and overall survival [4]. The only hope for cure from gastric cancer is the curative resection which currently can be performed in approximately 50% of newly diagnosed cases. For those curatively resected patients, the evaluation of prognostic factors is essential to predict survival and the incidence of tumor recurrence [5]. The nodal stage is the factor with the highest predictive value but there is a wide variety of further markers which influence the further clinical course [6]. TNM-associated criteria as well as other pathohistological factors like the classification according to Lauren are well accepted prognostic markers [5]. Moreover, there is a rapidly growing number of molecular-based markers both influencing individual therapy and predicting individual prognosis. In this context, the value of the tumor size is not fully understood. Several authors judged tumor size to be a significant prognostic marker for gastric cancer [7-10]. In other solid tumor entities, tumor size is included in various staging systems. Tumor size is a well-established predictive factor in parenchymal organ malignancies, such as thyroid gland or the liver. More recently, tumor size has been shown to be a predictive factor for survival and recurrence in tumors derived from non-parenchymal organs, too. Tumor size can be measured preoperatively by via endoscopy whereas the accurate estimation of the depth of tumor invasion can be performed only after the tumor resection. Thus, tumor size is a preoperatively available parameter.

With our study, we intended to analyze the prognostic value of tumor size as related to the main tumor stages for resected gastric cancer.

Patients and Methods

Patient cohort, inclusion and exclusion criteria

From 1995 to 2012 we treated 1074 patients with gastric cancer in our Department of General, Visceral and Vascular Surgery. 752 of these patients underwent gastric resection. In 573 cases the tumor size was clearly identified. We used a prospectively maintained gastric cancer data base to collect detailed demographical, clinical and pathohistological data from these patients. All patients with adenocarcinomas of the stomach and information on its size who underwent resection were considered for our study. Patients with permanent immunosuppression as well as those who had a neuroendocrine tumor differentiation were excluded from the study. In addition, we did not enrol emergency resections as well as procedures which had been performed for cases which were refractory to interventional treatment of severe tumor-associated complications (palliatively intended resections).

Definitions

To stratify the cases of our study group, we used the TNM classification from 1997 because the majority of gastric cancers included in this study were diagnosed before 2010. Those cases which were included from 2010 onward we converted to the original classification system.

Tumor measurement and definition of cut off point

Tumor size was measured after surgical resection by the pathologist and was defined as the largest diameter of macroscopically detectable tumor mass.

To identify the optimal cut off point, we stratified all measured tumor sizes in centimetre groups (1 to 10 millimetres as 1 centimetre, 11 to 20 millimetres as 2 centimetres and so on). As a second step, we analyzed these categorical data by using the Cox regression model. The position with the highest chi square value was chosen as the optimal cut off point.

Statistical methods and literature search

Data collection and statistical analysis were performed using SPSS 19.0. For the univariate analysis, categorical data were evaluated by cross-linked tables and the exact Fisher-test. The results were regarded as statistically significant if the p-value was lower than 0.05. The Kaplan-Meyer method was used for survival analyses.

For comparison of subgroups, statistical significance was measured by the log rank test. For the multivariate analysis, we used the Cox regression model and included all criteria with a p-value below 0.1 in the univariate analysis.

Medline was searched for literature using the following search strategy: (“gastric cancer” or “gastric adenocarcinoma”) and (“tumor size”) and (“survival” or “outcome” or “clinicopathological factors” or “prognostic factors” or “predictive factors”).

Results

General description of the study group

The study group consisted of 223 women (38.8%) and 350 men (61.3%). Patient age ranged from 23 to 94 years with a median age of 66 years. All patients underwent gastric resection.

Tumor size and definition of the cut off point

The tumor size ranged from 2 to 200 mm and had a median value of 45 mm. The Cox regression showed the optimal cut off point to be 4 cm with a maximum chi square value of 40.725 (p=0.000). Details of the analysis are shown in Table 1. Figure 1 shows that the most frequent tumor size was 3 cm followed by 4 cm.