Evaluating the effect of tumor size on survival and its prognostic significance among gastric cancer patients
1 UNIVERSITY OF HEALTH SCIENCES KARTAL KOSUYOLU HIGHER SPECIALTY TRAININ AND RESEARCH HOSPITAL, GASTROENTEROLOGY SURGERY CLINIC, ISTANBUL, TURKEY
Abstract
Purpose. This study investigates the prognostic significance of tumor size and its effect on survival among patients undergoing gastrectomy and D2 lymph node dissection due to gastric cancer. Materials and Methods. The clinicopathological characteristics of 320 patients who were operated due to gastric cancer between November 2006 and September 2019 were assessed retrospectively, of which 271 were included in the present study. A receiver-operating characteristic curve (ROC) analysis was carried out to identify the tumor size cut-off value. Patients were divided into small-size and large-size tumor groups. Clinicopathological characteristics were assessed using Chi-square and Mann-Whitney U tests, while survival was assessed with a Kaplan-Meier log-rank test. Results. The cut-off gastric cancer tumor size value was calculated as 4.75 cm. A statistical difference was noted in the tumor depth of wall invasion (p<0.001), the number of positive lymph nodes removed (p<0.001), vascular invasion (p=0.001) and perineural invasion (p=0.001) of the two groups. Survival was poorer in patients with large-size tumors than in those with small-size tumors (62 months vs. 88 months, respectively; p<0.001), and tumor size was associated with wall invasion depth (p<0.001) and Borrmann’s classification (p=0.002). A univariate analysis revealed tumor size to be a prognostic factor for survival (p=0.001), while no such finding could be established in a multivariate analysis (p=0.637). Conclusion. Tumor size is a prognostic marker for gastric cancer, and a preoperative assessment in this regard may suggest neoadjuvant therapy.
Introduction
Gastric cancer is the sixth most common type of cancer around the world, and among the leading causes of cancer death [1]. Aside from in Asian countries such as Japan and South Korea, gastric cancer generally presents at an advanced stage [2]. Early gastric cancer is typically treated using endoscopic methods, while the treatment for advanced stage gastric cancer is surgical resection and D2 lymph node dissection, along with pre- or post-operative therapies under a multidisciplinary approach [3]. The 5-year survival rate is above 90% in early gastric cancer with the mentioned approaches, but drops to as low as 30% depending on the stage [2].
Several prognostic indicators of gastric cancer have been identified, with the most indicative being lymph involvement and wall invasion depth, determined from postoperative pathological specimens [4,5]. Other postoperative histopathological prognostic factors include venous invasion, perineural invasion, surgical margins, peritoneal cytology and tumor size [6,7]. Tumor size is the main prognostic indication of certain solid organ tumors, such as those of the breast and liver, but is absent from the tumor, node and metastasis (TNM) staging system for gastric cancer [8]. There have been studies supporting the prognostic significance of tumor size in gastric cancer, while others make no such observation [8].
In the present study we investigate the prognostic significance of tumor size, measured postoperatively, among patients operated due to gastric cancer.
Materials and Methods
A retrospective review was made of 320 patients, who were operated due to gastric cancer in the Health Sciences University Kartal Koşuyolu High Specialty Educational and Research Hospital in Turkey, between November 2006 and September 2019. Patient details were accessed from clinical records and pathology reports. The assessment date for the survival analysis was accepted as December 31, 2019. D2 lymph node dissections were performed in line with the recommendations of the Japanese Research Society for the Study of Gastric Cancer (JRSSG) [3], and the Tumor, Node, Metastasis (TNM) classification system devised by the American Joint of Committee on Cancer (AJCC) (8th Edition, 2018) was applied for staging [9]. Of the total, 15 patients with a positive peritoneal cytology, 10 patients with liver metastasis identified during surgery, six patients with a positive distal or proximal surgical margin, 12 patients who died within 60 days of surgery and six patients with a failed tumor size measurement were excluded from the study. The study subsequently included 271 patients. Surgery-related complications were considered as those occurring within the first 30 days following surgery.
Statistical Analysis The normality of numerical variables was analyzed using a Kolmogorov-Smirnov test, revealing a non-normal distribution based on p<0.05, and so median (IQR) values were used. Categorical variables were expressed as numbers and percentages. The optimal cut-off value for tumor size was established based on the results of a receiver-operating characteristic (ROC) curve analysis, and patients were divided into two groups according to the cut-off value.
A Chi-square test, a Fisher’s exact test and a Mann- Whitney U test were used to determine any statistical differences between categorical variables. Risk factors for tumor size were examined with a Binary Logistic regression analysis. The survival of the two groups was analyzed with a Kaplan-Meier test, and a log-rank test was used to identify any difference. The prognostic factors affecting overall survival were examined with a univariate and multivariate stepwise Cox regression analysis, and the statistical assessment was carried out using the SPSS 21 software package. A p value of <0.05 was considered statistically significant.
Results
Among the 271-person sample, tumor size ranged from 0.4 to 18.0 cm, with a median of 4.50 cm and a mean of 5.15±2.76 cm (Figure 1A). The optimal tumor size was established using the receiver-operating characteristic curve (ROC) method. The optimal cut-off value for tumor size was 4.75 cm, with a sensitivity of 62% and a specificity of 60% (Figure 1B). The patients were divided into two groups based on tumor size (small-size tumor ≤4.75 cm; large-size tumor >4.75 cm).
A comparison of the clinicopathological characteristics of the two groups revealed statistical differences in wall invasion depth (p<0.001), stage (p<0.001), the number of positive lymph nodes removed (p<0.001), vascular invasion (p=0.001) and perineural invasion (p=0.001) (Table 1). Most of the patients in the large-size tumor group were at stage 3 based on a wall invasion depth of T3 or T4, and an N stage of N3 (38.2% and 68.1%, respectively). Vascular invasion and perineural invasion were also more common in this group.
The risk factors for tumor size were examined with univariate and multivariate logistic regression analyses (Table 2), revealing risk factors of wall invasion depth (p<0.001), N stage (p<0.001), vascular invasion (p=0.001) and perineural invasion (p=0.001), according to the univariate analysis, while ulcerovegetative type according to Borrmann’s classification (p=0.002) and wall invasion depth (p<0.001) were the risk factors identified in the multivariate analysis.
Small tumor size
(≤4.75 cm) Large tumor size
(>4.75 cm)
n % n % p value Gender
Male 90 66.2% 94 69.6%
0.543 Female 46 33.8% 41 30.4% Location
Upper 33 24.3% 31 23.0%
0.212 Middle 27 19.9% 39 28.9%
Distal 76 55.9% 65 48.1% Neoadjuvant therapy
No 114 83.8% 111 82.2%
0.726 Yes 22 16.2% 24 17.8% Borrmann’s classification
Polypoid 16 12.3% 17 13.2%
0.145 Ulcerovegetative 29 22.3% 42 32.6%
Ulcero-infiltrative 85 65.4% 70 54.3% Lauren’s Classification
Intestinal 48 35.3% 41 30.4%
0.388 Diffuse 88 64.7% 94 69.6% Type of Surgery
Subtotal 77 56.6% 63 46.7%
0.101 Total 59 43.4% 72 53.3% Depth of invasion
T1 28 20.6% 3 2.2%
p<0.001** T2 21 15.4% 9 6.7%
T3 61 44.9% 56 41.5%
T4 26 19.1% 67 49.6% Stage
Stage I 35 25.7% 9 6.7%
p<0.001** Stage II 49 36.0% 34 25.2%
Stage III 52 38.2% 92 68.1% Vascular Invasion
Negative 67 49.6% 40 29.6%
0.001* Positive 68 50.4% 95 70.4% Perineural Invasion
Negative 60 44.8% 34 25.2%
0.001* Positive 74 55.2% 101 74.8% Complications
No 100 73.5% 98 72.6%
0.862 Yes 36 26.5% 37 27.4%
Median (IQR) Median (IQR) Age 60 (53–67) 32 (53–69) 0.196 Total number of lymph nodes 22 (16–33) 26 (19–32) 0.066 Number of positive lymph nodes 1 (0–5) 4 [1–12] p<0.001** Length of hospital stay 10 [8–14] 10 [8–13] 0.691 Univariate Analysis Multivariate Analysis OR (95.0% CI) p OR (95.0% CI) p Gender .853 (.512–1.422) 0.543 .994 (.522–1.893) 0.986 Age 1.014 (.993–1.035) 0.194 1.020 (.995–1.046) 0.120 Location
Upper
Middle
Distal
1.538 (.768–3.077)
.910 (.504–1.645)
215
2.018 (.874–4.663)
1.401 (.688–2.854)
0.258 Borrmann’s Classification
Polypoid
Ulcerovegatative
Ulceroinfiltrative
1.363 (.594–3.128)
.775 (.365–1.645)
0.148
1.629 (.583–4.548)
.471 (.186–1.194)
0.002* Lauren’s Classification 1.251 (.752–2.079) .388 .857 (.445–1.652) 0.645 Depth of invasion
T1
T2
T3
T4
4.000 (.963–16.613)
8.518 (2.468–29.748)
24.051 (6.728–85.976) p<0.001**
5.334 (.964–29.518)
10.929 (2.101–56.850)
35.975 (6.201–208.713)
p<0.001** N Stage
N0
N1
N2
N3
1.774 (.871–3.6129)
3.207 (1.521–6.763)
4.194 (2.248–7.823) p<0.001**
1.052 (.412–2.687)
1.269 (.476–3.386)
1.858 (.710–4.862)
0.506 Vascular Invasion 2.340 (1.419–3.859) 0.001* .906 (.425–1.932) 0.798 Perineural Invasion 2.409 (1.437–4.038) 0.001* 1.183 (.577–2.425) 0.647
OR: odds ratio, CI: confidence interval, *p<0.05, **p<0.001 A statistical difference was noted in overall survival between the two groups (p<0.001): The small-size tumor group had a mean survival time of 89 months, while the mean survival time was 62.5 months in the large-size tumor group (Figure 2, Table 3). The prognostic factors affecting survival were evaluated with univariate and multivariate stepwise Cox regression analyses for all patients (Table 4). According to the univariate analysis, the prognostic factors were tumor size (p=0.001), wall invasion depth (p<0.001), the total number of positive lymph nodes removed (p<0.001), the presence of vascular invasion (p<0.001) and the presence of perineural invasion; while the multivariate analysis identified prognostic factors of tumor localization (p=0.023), wall invasion depth (p<0.001), the total number of lymph nodes removed (p<0.001) and the total number of positive lymph nodes removed (p<0.001).
Tumor Size
Estimate (mean) ± Std. Error 95% CI p value Small tumor size (≤4.75 cm) 88.938±6.195 76.796–101.081 p<0.001** Large tumor size (>4.75 cm) 62.614±5.885 51.080–74.147 Overall 75.565±4.500 66.746–84.385 **p<0.001, CI: Confidence Interval Univariate Analysis Multivariate Analysis OR (95.0% CI) p OR (95.0% CI) p Gender .776 (.535–1.126) 0.182 1.215 (.803–1.838) 0.357 Age 1.007 (.993–1.021) 0.331 1.009 (.993–1.025) 0.278 Tumor size 1.849 (1.307–2.615) 0.001* 1.093 (.756–1.578) 0.637 Location
Upper
Middle
Distal
1.594 (.969–2.622)
1.069 (.681–1.676)
0.087
1.591 (.925–2.736)
.882 (.550–1.417)
0.023* Lauren’s Classification 1.377 (.952–1.993) 0.089 .934 (.626–1.395) 0.738 Depth of invasion
T1
T2
T3
T4
3.932 (.835–18.519)
7.983 (1.945–32.758)
18.820 (4.602–76.957)
p<0.001**
4.229 (.883–20.265)
5.188 (1.205–22.334)
9.522 (2.145–42.282)
0.001* Total number of lymph nodes .990 (.975–1.005) 0.191 .962(.943–.981) p<0.001** Number of positive lymph nodes 1.072 (1.056–1.088) p<0.001** 1.082 (1.057–1.108) p<0.001** Vascular Invasion 2.454 (1.668–3.610) p<0.001** 1.090 (.707–1.682) 0.695 Perineural Invasion 2.694 (1.766–4.109) p<0.001** 1.307 (.815–2.0959) 0.267
OR: odds ratio, CI: confidence interval, *p<0.05, **p<0.001
Table 1. Clinicopathological features according to tumor size
| Table 1. Clinicopathological features according to tumor size | ||||||
|---|---|---|---|---|---|---|
| Small tumor size | Large tumor size | |||||
| (≤4.75 cm) | (>4.75 cm) | |||||
| n | % | n | % | p value | ||
| Male | 90 | 66.2% | 94 | 69.6% | ||
| Gender | 0.543 | |||||
| Female | 46 | 33.8% | 41 | 30.4% | ||
| Upper | 33 | 24.3% | 31 | 23.0% | ||
| Location | Middle | 27 | 19.9% | 39 | 28.9% | 0.212 |
| Distal | 76 | 55.9% | 65 | 48.1% | ||
| No | 114 | 83.8% | 111 | 82.2% | ||
| Neoadjuvant therapy | 0.726 | |||||
| Yes | 22 | 16.2% | 24 | 17.8% | ||
| Polypoid | 16 | 12.3% | 17 | 13.2% | ||
| Borrmann’s | ||||||
| Ulcerovegetative | 29 | 22.3% | 42 | 32.6% | 0.145 | |
| classification | ||||||
| Ulcero-infiltrative | 85 | 65.4% | 70 | 54.3% | ||
| Lauren’s | Intestinal | 48 | 35.3% | 41 | 30.4% | |
| 0.388 | ||||||
| Classification | Diffuse | 88 | 64.7% | 94 | 69.6% | |
| Subtotal | 77 | 56.6% | 63 | 46.7% | ||
| Type of Surgery | 0.101 | |||||
| Total | 59 | 43.4% | 72 | 53.3% | ||
| T1 | 28 | 20.6% | 3 | 2.2% | ||
| T2 | 21 | 15.4% | 9 | 6.7% | ||
| Depth of invasion | p<0.001** | |||||
| T3 | 61 | 44.9% | 56 | 41.5% | ||
| T4 | 26 | 19.1% | 67 | 49.6% | ||
| Stage I | 35 | 25.7% | 9 | 6.7% | ||
| Stage | Stage II | 49 | 36.0% | 34 | 25.2% | p<0.001** |
| Stage III | 52 | 38.2% | 92 | 68.1% | ||
| Negative | 67 | 49.6% | 40 | 29.6% | ||
| Vascular Invasion | 0.001* | |||||
| Positive | 68 | 50.4% | 95 | 70.4% | ||
| Negative | 60 | 44.8% | 34 | 25.2% | ||
| Perineural Invasion | 0.001* | |||||
| Positive | 74 | 55.2% | 101 | 74.8% | ||
| No | 100 | 73.5% | 98 | 72.6% | ||
| Complications | 0.862 | |||||
| Yes | 36 | 26.5% | 37 | 27.4% | ||
| Median (IQR) | Median (IQR) | |||||
| Age | 60 (53–67) | 32 (53–69) | 0.196 | |||
| Total number of lymph | ||||||
| 22 (16–33) | 26 (19–32) | 0.066 | ||||
| nodes | ||||||
| Number of positive | ||||||
| 1 (0–5) | 4 [1–12] | p<0.001** | ||||
| lymph nodes | ||||||
| Length of hospital stay | 10 [8–14] | 10 [8–13] | 0.691 |
Table 2. Logistic Regression Analysis of the Risk Factors for Tumor Size
| Table 2. Logistic Regression Analysis of the Risk Factors for Tumor Size | ||||
|---|---|---|---|---|
| Univariate Analysis | Multivariate Analysis | |||
| OR (95.0% CI) | p | OR (95.0% CI) | p | |
| Gender | .853 (.512–1.422) | 0.543 | .994 (.522–1.893) | 0.986 |
| Age | 1.014 (.993–1.035) | 0.194 | 1.020 (.995–1.046) | 0.120 |
| Location | 215 | 0.258 | ||
| Upper | ||||
| Middle | 1.538 (.768–3.077) | 2.018 (.874–4.663) | ||
| Distal | . 9 1 0 ( . 5 04–1.645) | 1.401 (.688–2.854) | ||
| Borrmann’s Classification | 0.148 | 0.002* | ||
| Polypoid | ||||
| Ulcerovegatative | 1.363 (.594–3.128) | 1.629 (.583–4.548) | ||
| Ulceroinfiltrative | .775 (.365–1.645) | .471 (.186–1.194) | ||
| Lauren’s Classification | 1.251 (.752–2.079) | .388 | .857 (.445–1.652) | 0.645 |
| Depth of invasion | p<0.001** | p<0.001** | ||
| T1 | ||||
| T2 | 4.000 (.963–16.613) | 5.334 (.964–29.518) | ||
| T3 | 8.518 (2.468–29.748) | 10.929 (2.101–56.850) | ||
| T4 | 24.051 (6.728–85.976) | 35.975 (6.201–208.713) | ||
| N Stage | p<0.001** | 0.506 | ||
| N0 | ||||
| N1 | 1.774 (.871–3.6129) | 1.052 (.412–2.687) | ||
| N2 | 3.207 (1.521–6.763) | 1.269 (.476–3.386) | ||
| N3 | 4.194 (2.248–7.823) | 1.858 (.710–4.862) | ||
| Vascular Invasion | 2.340 (1.419–3.859) | 0.001* | .906 (.425–1.932) | 0.798 |
| Perineural Invasion | 2.409 (1.437–4.038) | 0.001* | 1.183 (.577–2.425) | 0.647 |
| OR: odds ratio, CI: confidence interval, *p<0.05, **p<0.001 |
Table 3. Overall survival comparison by tumor size using Kaplan-Meier method
| Table 3. Overall survival comparison by tumor size using Kaplan-Meier method | |||||||
|---|---|---|---|---|---|---|---|
| Tumor Size | |||||||
| Estimate (mean) ± Std. Error | 95% CI | p value | |||||
| Small tumor size (≤4.75 cm) | 88.938±6.195 | 76.796–101.081 | p<0.001** | ||||
| Large tumor size (>4.75 cm) | 62.614±5.885 | 51.080–74.147 | |||||
| Overall | 75.565±4.500 | 66.746–84.385 | |||||
| **p<0.001, CI: Confidence Interval | |||||||
| Table 4. The prognostic factors for survival univariate and multivariate Cox regression analyses for all patients | |||||||
| Univariate Analysis | Multivariate Analysis | ||||||
| OR (95.0% CI) | p | OR (95.0% CI) | p | ||||
| Gender | .776 (.535–1.126) | 0.182 | 1.215 (.803–1.838) | 0.357 | |||
| Age | 1.007 (.993–1.021) | 0.331 | 1.009 (.993–1.025) | 0.278 | |||
| Tumor size | 1.849 (1.307–2.615) | 0.001* | 1.093 (.756–1.578) | 0.637 | |||
| Location | 0.087 | 0.023* | |||||
| Upper | |||||||
| Middle | 1.594 (.969–2.622) | 1.591 (.925–2.736) | |||||
| Distal | 1.069 (.681–1.676) | .882 (.550–1.417) | |||||
| Lauren’s Classification | 1.377 (.952–1.993) | 0.089 | .934 (.626–1.395) | 0.738 | |||
| Depth of invasion | p<0.001** | 0.001* | |||||
| T1 | |||||||
| T2 | 3.932 (.835–18.519) | 4.229 (.883–20.265) | |||||
| T3 | 7.983 (1.945–32.758) | 5.188 (1.205–22.334) | |||||
| T4 | 18.820 (4.602–76.957) | 9.522 (2.145–42.282) | |||||
| Total number of lymph nodes | .990 (.975–1.005) | 0.191 | .962(.943–.981) | p<0.001** | |||
| Number of positive lymph nodes | 1.072 (1.056–1.088) | p<0.001** | 1.082 (1.057–1.108) | p<0.001** | |||
| Vascular Invasion | 2.454 (1.668–3.610) | p<0.001** | 1.090 (.707–1.682) | 0.695 | |||
| Perineural Invasion | 2.694 (1.766–4.109) | p<0.001** | 1.307 (.815–2.0959) | 0.267 | |||
| OR: odds ratio, CI: confidence interval, *p<0.05, **p<0.001 |
Table 4. The prognostic factors for survival univariate and multivariate Cox regression analyses for all patients
| Table 3. Overall survival comparison by tumor size using Kaplan-Meier method | |||||||
|---|---|---|---|---|---|---|---|
| Tumor Size | |||||||
| Estimate (mean) ± Std. Error | 95% CI | p value | |||||
| Small tumor size (≤4.75 cm) | 88.938±6.195 | 76.796–101.081 | p<0.001** | ||||
| Large tumor size (>4.75 cm) | 62.614±5.885 | 51.080–74.147 | |||||
| Overall | 75.565±4.500 | 66.746–84.385 | |||||
| **p<0.001, CI: Confidence Interval | |||||||
| Table 4. The prognostic factors for survival univariate and multivariate Cox regression analyses for all patients | |||||||
| Univariate Analysis | Multivariate Analysis | ||||||
| OR (95.0% CI) | p | OR (95.0% CI) | p | ||||
| Gender | .776 (.535–1.126) | 0.182 | 1.215 (.803–1.838) | 0.357 | |||
| Age | 1.007 (.993–1.021) | 0.331 | 1.009 (.993–1.025) | 0.278 | |||
| Tumor size | 1.849 (1.307–2.615) | 0.001* | 1.093 (.756–1.578) | 0.637 | |||
| Location | 0.087 | 0.023* | |||||
| Upper | |||||||
| Middle | 1.594 (.969–2.622) | 1.591 (.925–2.736) | |||||
| Distal | 1.069 (.681–1.676) | .882 (.550–1.417) | |||||
| Lauren’s Classification | 1.377 (.952–1.993) | 0.089 | .934 (.626–1.395) | 0.738 | |||
| Depth of invasion | p<0.001** | 0.001* | |||||
| T1 | |||||||
| T2 | 3.932 (.835–18.519) | 4.229 (.883–20.265) | |||||
| T3 | 7.983 (1.945–32.758) | 5.188 (1.205–22.334) | |||||
| T4 | 18.820 (4.602–76.957) | 9.522 (2.145–42.282) | |||||
| Total number of lymph nodes | .990 (.975–1.005) | 0.191 | .962(.943–.981) | p<0.001** | |||
| Number of positive lymph nodes | 1.072 (1.056–1.088) | p<0.001** | 1.082 (1.057–1.108) | p<0.001** | |||
| Vascular Invasion | 2.454 (1.668–3.610) | p<0.001** | 1.090 (.707–1.682) | 0.695 | |||
| Perineural Invasion | 2.694 (1.766–4.109) | p<0.001** | 1.307 (.815–2.0959) | 0.267 | |||
| OR: odds ratio, CI: confidence interval, *p<0.05, **p<0.001 |
Discussions
Gastric cancer is a frequently encountered disease that is usually associated with a poor prognosis, and is among the leading causes of cancer death. It is therefore important to establish the prognostic markers for gastric cancer to improve patient survival and to identify the best treatment options for the patient [10]. The most effective prognostic factors are tumor invasion depth, lymph node involvement and metastasis status, which are used for the staging of the disease [11]. Tumor size has prognostic value in several cancer types, such as liver cancer, breast cancer and lung cancer, and is included in the TNM classification system for such cancer types; however, the role of tumor size in estimating the prognosis in gastric cancer, and whether it should be included in gastric cancer staging, are as yet uncertain [8]. Although there have been many studies reporting the independent prognostic significance of tumor size in gastric cancer, a lack of consensus remains due to the limited sample sizes and the variety of cut-off values established [8].
Del Rio P. et al. determined a cut-off value of 2.5 cm in their study dividing patients into small-size (<2.5cm), medium-size (2.5–5 cm) and large-size (>5cm) groups [12]. The authors found those with a tumor size of ≥2.5 cm to have a poorer prognosis, and tumor size was found to be associated with wall invasion depth and lymph node involvement [12]. In a gastric signet ring cell carcinoma study by Zhou L. et al., a cut-off value of 4.9 cm was identified in patients in two groups, and wall invasion depth and lymph node status were reported to produce differences between the groups. The large-size tumor group recorded poorer survival, while tumor size was associated with T3, T4a and T4b in a multivariate Cox regression analysis [13]. The T3-T4bN0M0 gastric cancer study by Chen S. et al. identified a cut-off value of 4.75 cm in a comparison of two groups, and reported differences in tumor localization and CEA levels between the two groups. The large-size tumor group had poorer survival, and tumor size had prognostic significance [14]. The study by Dittmar Y. et al. determined a cut-off value of 4.0 cm and reported differences in wall invasion depth, lymph node involvement status, lymphovascular invasion, perineural invasion, Borrmann’s classification, Lauren’s classification and the presence of intestinal metaplasia between the two groups [15]. The authors found survival to be poorer in gastric cancer patients with large-size tumors than in those with small-size tumors (31 months and 183 months, respectively) [15]. The ROC analysis in the present study was applied to determine the cut-off value, and resulted in a prognostic value of 4.75 cm. A difference was noted in wall invasion depth, the number of positive lymph nodes removed, vascular invasion and perineural invasion between the two groups. A univariate analysis of tumor size identified wall invasion depth, lymph node involvement, and vascular and perineural invasion depths as prognostic risk factors, while the depth of wall invasion by the tumor and Borrmann’s classification were identified as prognostic factors in the multivariate analysis. Survival was shorter in the large-size tumor group than in the small-size group (62 months vs. 88 months, respectively), and while tumor size was found to be a prognostic factor for overall survival in a univariate analysis, the multivariate analysis produced no such finding.
The limitations of the present study include its retrospective and single-center design and its small sample size.
Conclusions
As a conclusion, despite the decrease in incidence, gastric cancer is still one of the leading causes of cancer death. Tumor size is an important prognostic factor that is easy to measure endoscopically and radiologically prior to treatment planning, and can therefore be assessed as a marker in patients who cannot be assessed for tumor invasion depth and lymph node involvement for neoadjuvant therapy in the preoperative period.
Author Contributions
Uzun O, Senger AS, Gülmez S and Omeroglu S performed most of the study and literature search. Uzun O, Ofluoglu CB, Oz A designed the study and analyzed the data. Uzun O done statistical analysis, Uzun O, Senger AS, Gülmez S, wrote the manuscript, and Polat E and Duman M revised the manuscript. Uzun O and Duman M approved the final version of the manuscript.
Institutional Review Board Statement
Any aspect of the work covered in this manuscript has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript.
Conflicts of Interest
There are no known conflicts of interest in the publication of this article. The study protocol was approved by the Kartal Koşuyolu High Specialty Training and Research Hospital Ethics Committee with the number 2020.4 / 26-331. A written informed consent was obtained from each participant. The study was conducted in accordance with the principles of the Declaration of Helsinki. The manuscript was read and approved by all authors.
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