Previous studies have reported a poor prognosis for AFP-GC with lymphatic and venous invasion, along with high rates of liver metastasis as compared with non-AFP-GC [4, 8, 9]. In a study by Liu et al., the authors reported that the 1-, 3-, and 5-year survival rates of AFP-GC were 53%, 35%, and 28%, respectively [6]. However, Kripp et al. described a long-term survival case of unresectable AFP-GC of the esophago-gastric junction with several liver metastases, which was successfully treated with capecitabine- and oxaliplatin-based combination therapy [10]. Of note, Shibata et al. also reported the case of a patient who underwent both distal gastrectomy for early AFP-GC and left hepatectomy 20 months later. The patient survived without any recurrence for over 11 years after the first diagnosis [11]. Thus, recently, there has been an increase in the number of reports on AFP-GC patients with long-term survival because of multimodal treatments [6, 12, 13].
Our case highlights three key learning points: first, the long-term (i.e., 15 years) dormancy following the initial gastrectomy until the identification of the solitary metastasis to the mesentery; second, the multiple liver metastases, which went unobserved for 15 years, were evident only 2 months after the second surgery; and last, the disappearance of liver metastases for 5 years following only two courses of chemotherapy with S-1+CDDP.
Gastric cancer usually recurs within the first 2 years of gastrectomy. Late recurrences are rare, with approximately < 1% cases recurring after 10 years [14]. Prognostic factors for early recurrence, such as clinical stage, tumor size, depth of invasion, and lymph node involvement, are not useful in predicting late cancer recurrence [15]. The phenomenon of late recurrence has been partially explained by tumor dormancy. Specifically, it has been shown that dormancy can be present in the form of an early stage in tumor development, as a micrometastasis, or as minimal residual disease post-surgical removal or treatment of the primary tumor [16,17,18]. In gastric cancer, minimal residual disease was revealed in the blood, bone marrow, negative lymph nodes, and peritoneal cavity [19]. Till date, transition mechanism from dormancy to recurrence has not been completely explained, particularly in gastric cancer. Although precise mechanisms remain to be elucidated, increasing evidence suggest that many cancer patients suffer from metastatic relapse several years after they have undergone radical surgery [18]. Thus, the second surgery reactivated the tumor cells which were dormant for 15 years. Additional studies aimed at better understanding of tumor dormancy are necessary to predict late recurrence and to strengthen the follow-up protocol for long-term survivors of gastric cancer.
In an earlier study, Adachi et al. analyzed 270 AFP-GC cases. The authors reported that the 5-year survival rate and median survival period in all patients were 22% and 14 months, respectively. However, they found that patients with curative gastrectomy comprised 42% of the study cohort and median survival period was 29 months [5]. Of note, Inoue et al. analyzed 53 AFP-GC cases reporting a 5-year survival rate of 34% (18/53) [20]. Our patient was alive 15 years after a curative distal gastrectomy, until the recurrence of mesentery of jejunum.
In Japan, SP therapy for unresectable and recurrent gastric cancers has been recognized as the standard therapy [21]. At the time of diagnosis, our patient was expected to have a poor prognosis due to recurrence of AFP-GC. However, only two courses of chemotherapy with SP were extremely effective on metachronous liver metastases. Surprisingly, the patient is alive without any sign of recurrence at 7 years after the second surgery. With the development of chemotherapy strategies, there are increasing cases who achieved complete response by only several courses of chemotherapy in unresectable gastric cancer [22, 23]. Further accumulation of cases is required for selecting such patients.
