Subsite-specific metastatic organotropism and risk in gastric cancer: A population-based cohort study of the US SEER database and a Chinese single-institutional registry

Abstract

Background: Studies exploring whether metastatic organotropism and risk in gastric cancer (GC) differ by primary anatomical site are scarce.

Methods: This study included 15,260 and 1623 patients diagnosed with GC from the Surveillance, Epidemiology, and End Results (SEER) registry database and the Nanfang Hospital in China, respectively. Patients were stratified according to primary site of GC, and the incidence of metastasis to different organs was used to determine the metastatic organotropism for each GC subsite. Finally, the metastatic organotropism and risk were compared among the different subsite groups.

Results: Liver metastasis was the most common metastasis site in cardia GC, whereas other-site metastases were more common in the body, antrum, overlapping lesions, and unspecified GCs. Liver and other-site metastases were also frequently observed in the fundus, pylorus, lesser curvature, and greater curvature GCs. Patients with GC with definite primary tumor sites in the SEER and validation Nanfang hospital cohorts were compared by grouping as proximal and distal GCs for further analysis. In the SEER cohort, the top three metastatic sites of proximal GC were liver (21.4%), distant lymph node (LN) (14.6%), and other-site (mainly peritoneum, 11.9%), whereas those of distal GC were other-site (mainly peritoneum, 19.5%), liver (11.8%), and distant LN (9.5%). The incidence of metastasis to the liver, distant LN, lung, and brain was significantly higher in patients with proximal GC than in those with distal GC in both the SEER and Nanfang cohorts (p < 0.05). However, metastasis to other-site/peritoneum was significantly lower in patients with proximal GC compared to those with distal GC in the Nanfang Hospital and SEER cohorts, respectively (p < 0.05).

Conclusion: Liver and distant LN are the preferred metastatic sites for proximal GC, whereas peritoneal metastasis is more common in distal GC. Proximal GC has a higher risk of lymphatic and hematogenous metastases, and a lower risk of transcoelomic metastasis than distal GC. Our findings highlight the need to stratify GC by its primary subsite to aid in planning and decision-making related to metastatic management in clinical practice.

Keywords: gastric cancer; metastatic management; metastatic organotropism; metastatic risk; primary tumor location.

FIGURE 1

The metastatic incidences to different sites in gastric cancers with different primary anatomical subsites. The metastatic incidences of gastric cancer originated in (A) all, (B) cardia, (C) fundus, (D) body, (E) antrum, (F) pylorus, (G) lesser curvature, (H) greater curvature, (I) overlapping lesion, and (J) not otherwise specified location in the SEER cohort. The presence of the different lowercase letter above the bars denotes a significant difference between groups (p < 0.05).

FIGURE 2

The metastatic incidences among gastric cancers with different primary anatomical subsites. The risk of (A) all, (B) liver, (C) distant lymph nodes, (D) lung, (E) bone, (F) brain, and (G) other‐site metastases among gastric cancers with different primary anatomical subsites in the SEER cohort. The dashed line indicates the average metastatic incidence in each organ. The presence of the different lowercase letter above the bars denotes a significant difference between groups (p < 0.05).

FIGURE 3

The metastatic incidences of proximal and distal gastric cancers in the Nanfang Hospital and SEER cohorts. The metastatic incidences of gastric cancer in (A) Nanfang Hospital and (B) SEER cohort; the metastatic incidences of proximal gastric cancer in (C) Nanfang Hospital and (D) SEER cohort; the metastatic incidences of distal gastric cancer in (E) Nanfang Hospital and (F) SEER cohort. The presence of the different lowercase letter above the bars denotes a significant difference between groups (p < 0.05).

FIGURE 4

The metastatic incidences between proximal and distal gastric cancers. The risk of (A) liver, (B) distant lymph nodes, (C) lung, (D) bone, (E) brain, and (F) other‐site metastases between proximal and distal gastric cancers in the SEER cohort; the risk of (G) liver, (H) distant lymph nodes, (I) lung, (J) bone, (K) brain, and (L) peritoneal metastases between proximal and distal gastric cancers in the Nanfang Hospital cohort; (M) the odds ratios of metastatic incidences between proximal and distal gastric cancers in the logistic regression model adjusting for the potential confounding effects of age, sex, race, grade, chemotherapy, surgery, and radiation. The presence of the different lowercase letter above the bars denotes a significant difference between groups (p < 0.05).

FIGURE 5

Schematic diagram of the present study. Metastatic organotropism and risk vary according to the anatomical subsite of GC. Liver and distant LNs are the preferred metastatic sites for proximal GC, whereas peritoneal metastasis is more common in distal GC. Proximal GC has a higher risk of lymphatic and hematogenous metastases, including distant LNs, liver, lung, bone, and brain metastases, and a lower risk of transcoelomic metastasis, which mainly consists of peritoneal and ovarian metastases, compared to distal GC.