To predict the prognosis of cancer patients and to plan patient-specific treatment, it is essential to classify patients considering various prognostic factors. For these purposes, the AJCC TNM stage is widely accepted for most solid cancers, including gastric cancer . Also, T stage and N stage were demonstrated to be the most powerful prognostic factors of gastric cancer patients. In gastric cancer, the T stage reflects the depth of the tumor invasion, whereas tumor diameter is also involved in assessment of the T stage in many other cancers, such as breast cancer, lung cancer, and tongue cancer [15, 16].
In previous studies that investigated tumor diameter in gastric cancer, it was closely related with histologic type, lymph node metastasis, tumor invasion, vessel invasion, neural invasion and peritoneal metastasis . Saito et al.  found that tumor diameter could also be used to predict the recurrence site of gastric cancer. Moreover, Deng et al.  demonstrated that tumor diameter represented a better prognostic stratification ability compared with T stage. However, tumor diameter alone could not accurately reflect the actual tumor burden of gastric cancer due to this cancer’s complicated morphology and inconsistent pattern of invasion. Most of these studies have failed to demonstrate the validity of tumor diameter as an independent prognostic factor even if tumor diameter is considered as a significant prognostic parameter. Thus, a new index, such as tumor volume, which could better reflect the actual burden of these tumors is needed for investigation.
In numerous previous studies, investigators tried to estimate tumor volume with imaging tools, such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-computed tomography (CT), and their results sought that it was contributing to poor prognosis of patients [20–23]. However, in these studies, errors with the actual tumor range, including the inability to measure in image studies according to tumor shape and pattern, cannot be overlooked. Assessment of tumor volume based on histological measurements is varied in several previous studies, and there is no standardized formula worldwide [9, 10, 13]. In this study, we propose a new formula using histological measurements to assess tumor volume of gastric cancer. The formula used in this study included both the long and short axis, and the calculation of these parameters was applied based on previous cancer research literatures. In addition, DOI was weighted because, even for tumors with the same volume, we cannot ignore the effect of its depth in gastric cancer. Our results confirmed the validity of this calculation of TV, as the classification of patients using this values showed significant differences between groups in OS and DSF.
In the this study, we also analyzed the survival rates of cTV groups in each T and N stage to prove the effect of TV as a prognostic factor in the same stage. It was confirmed that the prognosis differed significantly according to tumor volume in T4 and N3 stage. However, as we expected, the effect of this tumor volume did not significantly affect prognosis in early gastric cancer. For early gastric cancer, it is difficult to estimate the tumor burden by volume compared to advanced gastric cancer due to morphological characteristics, such as a flat shape. Meanwhile, for advanced gastric cancer, the interactions between tumors burden and lymphovascular invasion would likely increase with increasing tumor volume. Therefore, as tumor volume increase, so would the probability of micrometastases migrating from the tumor through the lymphatic vessels, increasing the postoperative recurrence rate and resulting in poorer prognosis [20, 24, 25]. Moreover, for tumors that invade the serosa, thus penetrating the gastric wall, tumor size is likely associated with a larger area of serosal invasion, increasing the likelihood of intraperitoneal dissemination and poorer prognosis. At the same time, tumor stroma produces cytokines that modulate immune reactions, which are responsible for signal transduction and facilitate tumor invasiveness [26–28]. All of these factors increase the possibility of recurrence, leading to poorer prognosis.
The current study has some limitations. First, although we did our best to estimate the tumor volume, the obtained tumor volume is still not the true tumor volume. In fact, tumors have various shapes such as flat, fungating or ulcerative. And in principle, different formulas should be used to calculate each tumor volume [10, 13]. Thus, we tried to complement this problem by adding the effect of tumor invasion to the volume calculation currently used in many oncologic studies. Second, due to the limitations of the retrospective study design, the collection of information for adjuvant chemotherapy was insufficient. Depending on compliance with chemotherapy, it may be a variable in the prognosis of the patient. However, according to our institution's policy, patients with gastric cancer at the same stage generally follow the same treatment policy; thus, the results of subgroup analysis are more reliable. Furthermore, to establish a scientific basis, it is necessary to perform external validation using other patient cohorts.