Our study demonstrated that the 5-year OS rate of patients with MGC was 48.1%, which was significantly poorer than those with SGC (58.7%) (P = 0.013) and that MGC was an independent risk factor for survival (Hazard ratio [HR] = 1.378, 95% confidence interval [CI] 1.061–1.870, P = 0.039). Further, our results identified that postoperative adjuvant chemotherapy could improve the 5-year OS rate of patients with advanced MGC.
Although most GCs consist of only one single lesion, MGCs are not uncommon. The incidence of MGC in our study was 3.2%. Some scholars believe that MGCs are a special type of GC, and there are differences in clinicopathological characteristics between MGC and SGC. Mitsudomi et al. found that MGCs were more common in elderly men and early GC [4]. In a study by Otsuji et al., they also found that patients with MGC and SGC had significant differences in tumor size, macroscopic types, depth of invasion, and the extent of lymph node dissection [6]. However, some scholars also believe that there are similarities between some of the clinicopathological features of MGC and SGC [3, 17,18,19,20]. In our study, MGC and SGC had no statistically significant differences in terms of demographic characteristics, such as age, sex, BMI, family history. Regarding postoperative pathology, MGC had deeper depths of invasion, greater number of lymph node metastases, and more advanced pathological stages, suggesting that MGCs may have a more aggressive nature in contrast to SGC.
Currently, there are few studies relating to the prognosis of patients with MGC, but those existing have shown contrasting results. Borie et al. investigated 199 cases of SGC and 33 cases of MGC. Their results showed that the 5-year OS rate of early MGC was greater than 90%, and was comparable to that of early SGC [8]. But in a study by Maeta et al. who analyzed 2241 cases of SGC and 164 cases of MGC, they found that the long-term prognosis of MGC cases was poorer than those of SGC in both stages I–II and III–IV [21]. However, these studies had significant differences in their investigated clinicopathological data, between the MGC and SGC groups, which may have led to the observed conflicting findings. In this study, we included a larger number of cases to analyze the clinicopathological differences between MGC and SGC cases, and we used a propensity score matching method to balance the differences between these two groups of patients to further explore the predictors associated with the prognosis for patients with MGC. Our results showed that the 5-year OS rate of MGCs was lower than that of SGCs, and that MGC was an independent predictor for postoperative OS. The reasons to why MGC patients have poor prognosis are still inconclusive. In a study which included 1606 patients who underwent gastrectomy with a follow-up for about 19 years postoperatively, the authors found that patients with MGC were more prone to metachronous cancers in the colon, urogenital system, and other organs than those with SGC [22]. Therefore, it is possible that patients with MGC may be more susceptible to canceration of other organs due to genetic susceptibility, leading to the poor long-term prognosis. In addition, Eom et al. reported that the prevalence of missed diagnosis of MGC by preoperative endoscopy was as high as 29.5% [7]. For such cases, if they did not undergo total gastrectomy, they could experience a higher risk postoperative tumor recurrence. Therefore, considerable awareness should be given to the possibility of multifocal cancer in the stomach. The preoperative, intraoperative, and postoperative examination of specimens should be strengthened and meticulously performed to avoid missed diagnoses.
In addition, we investigated the impact that different types of gastrectomy may have on the prognosis of MGC, but our results demonstrated that the type of gastrectomy was not an independent predictor of prognosis for patients with MGC (P = 0.114, Fig. 3d).
Further, this is the first study to have investigated the impact of chemotherapy on the prognosis of MGC. In this study, the 5-year OS rate of advanced MGC patients who received adjuvant chemotherapy was 48.0%. Most patients with advanced GC were recommended to receive 6 to 8 cycles of adjuvant chemotherapy. However, this depended on the patient’s performance status, major organ functions, severity of comorbidities and their willingness to comply with implement adjuvant chemotherapy. In clinical practice, we have observed that some proportion of our patients, especially those from rural areas or those who underwent surgery in the past decades, were reluctant to accept or comply with regular visits for postoperative adjuvant chemotherapy as compared to those being diagnosed in the recent years, and we hypothesize that these may have partly contributed to the cause of why some patients with AGC were not adjuvantly treated.
As shown in Fig. 4, our study found that for AGC patients without adjuvant chemotherapy, the 5-year OS rate of MGC was inferior than that of SGC (34.0% vs. 46.1%, P = 0.025), while for those who had adjuvant chemotherapy, the 5-year OS rates of patients with MGC and SGC were comparable (48.0% vs. 53.3%; P = 0.292). Further, we found that the 5-year OS rate of advanced MGC patients with adjuvant chemotherapy was significantly higher than those without adjuvant chemotherapy (48.0% vs. 34.0%; P = 0.026). The efficacy of adjuvant chemotherapy for AGC has been confirmed by multiple prospective studies. In multicenter studies from Japan and South Korea, the 5-year OS rate of patients receiving adjuvant chemotherapy after surgery was significantly higher than that of patients undergoing radical surgery alone [23, 24], and similar results were observed in western studies [25, 26]. In our study, chemotherapy has demonstrated significant survival benefits in patients with advanced MGC, however, the optimal regimen for such category of patients is yet to be determined.
Despite demonstrating the impact of adjuvant chemotherapy on the long-term survival of patients with MGC, the present study has several limitations that need to be addressed. First, the retrospective and non-randomized nature of this study makes it subjective to certain selection bias. Second, since our database only recorded whether the enrolled patients had or did not have adjuvant chemotherapy, data regarding the specific number of chemotherapy cycles were incomplete, and we believe this may have had some impacts on the results obtained, to some extent. Third, since we were unable to obtain accurate data on the type of cancer relapse (local recurrence, peritoneal metastasis, or distant metastasis) from our database, we could not analyze if there was a difference in the type of relapse between MGC and SGC. Fourth, due to the limited cases of MGC in our study, we did not further classify N3 stage as N3a and N3b. Despite these limitations, this study provided a reliable insight on the outcomes of patients with MGC and could be used as a preliminary basis for prospective multicenter studies on the treatment selection for this category of patients.