Resecting Liver Metastases in Gastric Cancer?
Abstract & Commentary
Synopsis: Nineteen gastric cancer patients were studied who underwent a curative resection of liver metastases. The 5-year actuarial survival rate was 34%. Favorable prognostic factors included solitary rather than multiple metastases, and metachronous rather than synchronous occurrence.
Source: Okano K, et al. Ann Surg. 2002;235:86-91.
Unlike colorectal cancer, the clinical benefit of resecting hepatic metastases from gastric cancer is not widely accepted. To study this approach, Okano and colleagues from Japan retrospectively reviewed 807 gastric cancer patients over a 14-year period. There were 90 patients with hepatic metastases, 19 of which underwent a curative resection of the metastatic disease. The other 71 patients were inoperable due to peritoneal dissemination, para-aortic metastases, or numerous scattered metastases in both lobes.
The features of the primary tumor were analyzed. All cases were adenocarcinoma, and with one exception, invaded deeper than the muscularis propria. Excluding involved paraaortic nodes which eliminated eligibility for surgical resection of liver lesions, 84% of patients had metastatic disease in the resected regional lymph nodes.
The features of the metastatic tumor were also analyzed. There were 13 synchronous and 6 metachronous tumors. The median size of the hepatic lesions was 39 mm (range, 3-100 mm). The presence of a pseudocapsule was seen in 68% of cases.
The surgical approaches included anatomic resection (37%), limited resection (37%), or combined procedures (26%). The 1-month surgical mortality rate was zero. Eleven of the 19 patients received adjuvant chemotherapy which may have been delivered systemically, intra-arterially, or intraportally. Unfortunately, no details are provided regarding which drugs were used, how they were delivered, or for how many cycles.
With a median follow-up of 3 years, 14 of 19 patients (74%) had recurrent disease a median 20 months (range, 7-26 months) after hepatic resection. The majority of these recurrences were in the liver, with pulmonary and nodal recurrences also described.
Overall, despite having metastatic gastric cancer, surgically treated patients had 1-year, 3-year, and 5-year actuarial survival rates of 77%, 34%, and 34%, respectively. Three patients survived longer than 5 years. Although such comparisons must be viewed with suspicion, 9 of the unresectable patients (from the 90 patients with hepatic metastases) were, in retrospect, felt to be candidates for surgical resection. Without surgical intervention, their 1-year and 3-year actuarial survival rates were 43% and 0%, respectively.
A detailed analysis of prognostic factors was undertaken. Pathologic features, such as T stage, N stage, presence of peritumoral lymphocytes, lymphatic invasion or venous invasion, were not associated with outcome. On the other hand, both a well-differentiated histology and a peritumoral fibrous capsule were positive prognostic factors. Furthermore, the presence of metachronous or solitary metastases, but not tumor size or type of surgical procedure, was associated with a statistically significant improved survival. The use of postoperative chemotherapy was not associated with a clinical benefit.
Comment by Kenneth W. Kotz, MD
The June 2000 issue of Clinical Oncology Alert included a discussion about resecting liver metastases from breast cancer, another situation where the clinical benefit has not been clearly defined.1 The results of the study by Okano et al suggest that carefully selected patients with stomach cancer metastatic to liver can achieve prolonged survival after hepatic resection. Furthermore, their results suggest that patients with solitary lesions have a better outcome than multiple lesions. Unfortunately, because there are no details regarding the number of lesions in the latter group, the significance of this comparison is unclear. Their results also suggest that surgical therapy is most likely to be helpful for metachronous lesions, and those that are well-differentiated and contained within a pseudocapsule.
Improved or prolonged survival after hepatic resection of metastases from stomach cancer has been suggested by other series,2-5 as well as a number of case reports. These series, like Okano et al, have also reported that favorable prognostic factors include solitary rather than multiple tumors2 and a metachronous rather than synchronous occurrence.3 Unlike Okano et al, however, others have found the following factors to be prognostic: 1) hepatic tumor-free margin > 10 mm; 2) metastatic tumor size (5 cm cut-off); 3) disease-free interval > 1 year; and 4) presence of peritumoral lymphocytes.2,5
That 3 patients were alive at 81, 96, and 138 months, one of whom had 2 resections (synchronous and metachronous), is particularly noteworthy, contributing to the 5-year survival of 34% reported by Okano et al. Certainly, these results of resectable stage IV gastric cancer patients are encouraging. In fact, even pulmonary or nonhepatic intra-abdominal recurrences have been considered for surgical intervention, although others have found this approach to be futile for lung metastases.6,7
Essentially all published data of resecting liver metastases in gastric cancer, such as the study by Okano et al and others,2-7 come from Japan, where differences in gastric cancer epidemiology and survival data are well known.8 Therefore, one must question the applicability of their conclusions to gastric cancer patients seen in North America. Nevertheless, occasional carefully selected patients with metastatic gastric cancer to the liver may benefit from surgical intervention. Whether other liver-directed therapies such as radio frequency ablation would be as beneficial is of interest but remains unknown.
References
1. Kotz K. Clinical Oncology Alert. 2000;15(6):42-43.
2. Miyazaki M, et al. Am J Gastroenterol. 1997;92: 490-493.
3. Takada Y, et al. Hepatogastroenterology. 2001;48: 83-86.
4. Saito A, et al. Hepatogastroenterology. 1996;43: 560-564.
5. Fujii K, et al. Hepatogastroenterology. 2001; 48: 368-371.
6. Takeyoshi I, et al. Hepatogastroenterology. 2000;47: 1479-1481.
7. Kanemitsu Y, et al. J Surg Onc. 1998;69:147-150.
8. Karpeh M, et al. In: DeVita D, et al, eds. Cancer: Principles & Practice of Oncology, 2001;1092-1121.
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