Prognostic Factors Of Gastric Cancer With Liver Metastases And The Evaluation Of Different Therapeutic Strategies

Background and Objectives:Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. The development of liver metastases is a frequent and fatal event for gastric cancer patients, however, standard therapeutic strategies has not been well established. In this study, we aimed to evaluate the role of surgery in the treatment of gastric cancer with synchronous liver metastases through the comparison among different therapeutic strategies. Furthermore, we investigated the prognostic factors and indications of surgical treatment. In the study for metachronous liver metastases, we sought to identify independent risk factors for interval time of liver metastases originating from gastric cancer after radical gastrectomy, analyze the survival time after the presence of metachronous liver metastases and investigate the prognostic factors of major clinical relevance.Methods:We retrospectively reviewed the records of the 594 patients of gastric cancer with synchronous liver metastases and 109 patients of metachronous liver metastases occurring more than six months after surgery. Survival time of 119 patients who received gastrectomy with chemotherapy and 95 patients who received chemotherapy alone with a KPS≥70 was followed up by telephone, mail or outpatient records, clinicopathological characteristics were compared between groups. Special attention was on the 35 patients who received gastrectomy plus hepatic surgical treatment in further analysis. The data of 109 patients with metachronous liver metastases was analyzed to evaluate significant risk factors for interval time of hepatic metastases originating from gastric cancer after radical gastrectomy and further investigation was done to evaluated the survival and prognostic factors.Results:The 1 years,2 years,3 years survival rate was 36.7%,15%,9.6% for gastrectomy plus chemotherapy group,20.7%,2.7%,0 for chemotherapy alone group, respectively(P<0.001).Multivariate analysis showed surgical treatment (P=0.002), degree of liver metastases(H)(P=0.009), extra-hepatic metastases (P=0.013), transarterial chemoembolization (P=0.045) were independent prognostic factors. Further subgroup analysis showed the survival benefit of surgical treatment was only observed in H1, H2 liver-only metastases patients (P<0.001) but not in H3 liver-only metastases (P=0.325) or patients with extra-hepatic metastases (P=0.59). Survival benefit was not significant in patients of primary gastric tumor size≥8cm (P=0.165).Among the 105 cases of liver-only metastases patients who received gastrectomy, the median survival time (MST) for patients received gastrectomy without hepatic surgical treatment was 10 months compared with 15 months of patients who received synchronous hepatic surgical treatment(P=0.003). Multivariate survival analysis revealed that the extend of lymphadenectomy(D), (P<0.001), N(P<0.001), H(P=0.005), lymphovascular invasion (P=0.002) were significant independent prognostic factors for survival. Among patients received D2 lymphadenectomy, hepatic surgical treatment significantly improved the survival compared with those received gastrectomy alone (MST:24months vs.12months, P=0.001). However, hepatic surgical treatment was not a prognostic factors for patients received D1 lymphadenectomy (MST:8months vs.8months, P=0.790). For the 35 patients who received gastrectomy plus hepatic surgical treatment, D2 lymphadenectomy(P<0.001), H(P=0.017), N(P=0.015) were independent significant prognostic factors for survival.The median time interval for liver metastases free survival of the 109 patients who underwent radical gastrectomy is 15 months. The liver metastases free survival rate at 1-,2-,3-,5-,10-year was 58.7%,30.3%,21.1%,11%,5.5%, respectively. In most of these patients (69.7%), the diagnosis of metachronous liver metastases was made within 2 years after surgical treatment. Cox regression analysis identified N (P=0.025), lymphovascular invasion (P<0.001) as independent predictors affecting liver metastases free survival. The 1-,2-,3-,5-year survival rates were 47.0%,19.2%, 7.7%,0%,respectively, with an MST of 12 months. Multivariate survival analysis indicated N(P=0.011), H (P<0.001), active treatment (P<0.001) were independent prognostic factors for survival since the presence of liver metastases. Among patients with H1, H2 liver metastases, the MST for patients in hepatic surgical treatment group, TACE group and systemic chemotherapy alone group was 26,14,12 months, respectively. Survival rate in hepatic surgical treatment group was significantly higher comparing with systematic chemotherapy alone group(P=0.019), no significant survival difference was observed between hepatic surgical treatment group and TACE group, or between TACE group and systemic chemotherapy group. Among H3 liver metastases patients, the MST for TACE group and systemic chemotherapy group was 9 months and 5 months, respectively, but the difference was not significant(P=0.180).Conclusion:Surgical treatment might prolong the survival for patients of gastric cancer with liver metastases. For synchronous liver metastases, surgical treatment should be performed if the performance status is permitted. H1,H2 liver-only metastasis patients with primary gastric tumors size<8 should be considered appropriate candidates before embarking on systematic chemotherapy alone.For gastric cancer with synchronous liver metastases without extra-hepatic metastases, D2 lymphadenectomy is the prerequisite for achieving the survival benefit of hepatic surgical treatment. Patients with low degree of lymph node metastasis and H1 liver metastases would make the appropriate candidates for hepatic surgical treatment.In most of metachronous liver metastases patients, diagnosis was made within 2 years after surgical treatment. As a result, liver examinations should be performed regularly, especially within the first 2 years after surgical treatment, and should be continued for 5 years, and especially for patients at risk. Active treatment strategies may prolong patients' survival compared with supportive treatment only. For patients with H1, H2 metachronous liver metastases patients, hepatic surgical treatment may bring more survival benefits compared with systemic chemotherapy alone.