We describe a patient with stage IV gastric cancer with multiple liver metastases who successfully underwent gastrectomy and hepatectomy as conversion surgery after second-line chemotherapy with RAM and PTX. Moreover, pathological examination showed that lymph node metastasis and liver metastases disappeared due to chemotherapy. Although the RAINBOW trial showed that second-line chemotherapy with RAM and PTX contributes to prognostic improvements, including improvements in tumor response, in patients with unresectable advanced gastric cancer, the clinical significance of conversion surgery in responders to chemotherapy with RAM and PTX remains unclear [3]. We searched for literature on conversion surgery after second-line chemotherapy for gastric cancer in the PubMed database using the terms "gastric cancer" and "conversion surgery" and excluded articles published only in abstract form. To our knowledge, this is the third report on conversion surgery after second-line treatment with RAM-based chemotherapy in patients with advanced gastric cancer [12, 13].
Despite remarkable advances in chemotherapy, the prognosis of patients with stage IV gastric cancer remains poor. The liver is the most common site of distant metastasis from gastric cancer, and the incidence of liver metastasis is reported to be 48% in patients with metastatic gastric cancer [14]. Surgical resection is generally recommended for patients with colorectal cancer who have liver metastases that are amenable to R0 resection [15]. In contrast, the clinical impact of surgical resection for liver metastases from gastric cancer remains controversial. However, recent studies have demonstrated that hepatectomy may have clinical significance for improving prognosis in patients with liver-limited metastasis from gastric cancer [7, 8]. Oki et al. reported 3- and 5-year postoperative OS rates of 51.4% and 42.1%, respectively, in 94 patients with liver-limited metastasis who underwent surgery [7]. They concluded that patients with a single liver metastasis from gastric cancer with a nodal status of < N2 might be good candidates for liver resection [7]. Similarly, in their study of 44 patients with liver metastasis from gastric cancer with or without other metastases who were treated with chemotherapy, Arigami et al. found that patients with no peritoneal dissemination who responded to chemotherapy were good candidates for conversion surgery [8]. Despite weak evidence, the Japanese Gastric Cancer Treatment Guidelines also recommend surgical resection in patients with oligometastases who have no noncurative factors [2]. Our patient presented with liver-limited metastasis in the form of two metastatic liver nodules. Furthermore, staging laparoscopy revealed no peritoneal dissemination. Therefore, our patient may be a good candidate for conversion surgery.
Bevacizumab (BV) and RAM are anti-angiogenic agents associated with vascular endothelial growth factor. Therefore, these agents have been clinically suspected to increase postoperative morbidity after surgery by wound healing disorders. Kesmodel et al. recommended waiting at least 6 weeks from discontinuation of BV to surgery in patients undergoing hepatic surgery after neoadjuvant BV for colorectal cancer liver metastases [16]. On the other hand, there is actually little evidence available to judge the safety and optimal timing of surgery in patients with malignancies, including gastric cancer, who receive RAM-based chemotherapy. Consequently, further work is warranted to assess them in patients with stage IV gastric cancer who undergo conversion surgery after RAM-based chemotherapy.
The patient received SP as first-line chemotherapy. Although the primary tumor progressed after six courses of SP, the shrinkage of lymph node metastasis and liver metastases was maintained. These findings suggest that at least first-line chemotherapy including S-1 had a favorable response to these metastases. Moreover, the patient has a high recurrent potential of liver metastases. Accordingly, he received oral S-1 as an adjuvant chemotherapy.
Yoshida et al. proposed a new system for classifying stage IV gastric cancer based on tumor properties and described clinical indications for conversion surgery after chemotherapy [4]. They classified patients with stage IV gastric cancer into four categories, with category 2 denoting patients with marginally resectable metastasis [4]. Based on this classification, conversion surgery is recommended in responders classified as category 2, indicating a complete response or partial response to intensive chemotherapy [4]. According to this classification system, our patient was categorized as category 2. Accordingly, conversion surgery may be a therapeutic strategy for improving prognosis in this patient. High response rates and improvements in prognosis are expected with conversion surgery even after second-line and third-line chemotherapy. However, few studies have investigated the clinical impact of conversion surgery after second- and third-line chemotherapy. Consequently, further studies are required to assess the clinical indication and prognostic significance of conversion surgery in patients who respond to second- and third-line chemotherapy.