Patients with noncurative ER were recommended additional surgery for better survival benefits. Nevertheless, the existing researches had different perspectives and some patients would not be able to undergo additional surgery for various reasons. Therefore, this study was conducted to evaluate whether additional surgery was beneficial for patients with EGC who underwent noncurative ER.
This meta-analysis of 16 studies reported that surgery group had higher undifferentiated type, higher rate of SM2, lymphatic and vascular invasion, which indicated that these patients were more frequently selected for additional gastrectomy, yet, patients were older, the rate of the 5-year OS, 5-year DSS and 5-year DFS were lower in the observation group. The above factors may suggest that advanced age or additional surgery may be one of the important reasons that affected the prognosis. Although the long-term prognosis may be closely related to the age factor, the fact that the lower rate of recurrence or metastasis and the survival benefits of elderly patients in additional surgery group could strongly prove the advantages of additional gastrectomy. The study written by Suzuki et al.(23)with the help of propensity score matching that controlled different clinicopathological factors such as age, concomitant diseases showed similar results. The elderly tended to have more concomitant diseases or higher surgical risks, and the probability of rejecting subsequent surgery was greater, this may be an important reason for the age difference between the two groups. In short, additional gastrectomy may be one of the independent predictors for long-term results, and could improved survival benefits for these patients.
As shown in this article, the common reasons why part of elderly patients could not be treated with additional surgical treatment were that refusal of surgery or high surgical risks, including advanced age or adverse events(7, 14, 15, 17–21, 25). One article(27) demonstrated that after full considerations, only approximately 20% of patients would choose further gastrectomy among patients ≥ 80 years. The possible explanations were that ESD could keep the anatomy of the stomach intact, maintain normal physiological functions and a high quality of life, while various adverse events may arise due to the destruction of the integrity of the stomach after gastrectomy. Moreover, the aging process degrades physical conditions, the non tumor-related prognosis of the super-elderly patients (age ≥ 80 years) may be worse. In principle, we still strongly recommend additional gastrectomy for patients without obvious contraindications for better long-term survival. Significant evidences showed that advanced age, undifferentiated type, tumor size ≥ 2 cm, and presence of ulceration were important factors in causing noncurative ER(28, 29). If the elderly did not want to undergo surgery, the above individual characteristics should be evaluated in detail, fully communicated with the patients, and the benefits and risks should be weighed before finally deciding on the treatment plan.
However, the existing included studies seldom discuss whether the interval would affect the results. It had been reported that ulcers and fibrosis caused by ESD may affect subsequent gastrectomy(30). This was also a question worth pondering. One published study(31) reported that the survival benefit of delayed surgery after noncurative ER for EGC was equal to that of directed surgery with an average delay of 21.5 days. Similar result indicated that a better prognosis was obtained when the operation time was delayed by 1 month(32). In a word, it was recommended that the time interval between the completion of noncurative ER and the time of delayed surgery be at least 1 month to reduce its impact on the long-term outcomes. This theory may has important reference value for patients with noncurative ER who were hesitant about undergoing additional surgery, they could take longer to decide the next treatment plan. Endoscopic ultrasonography (EUS), infrared video endoscopy, magnifying endoscopy with narrow-band imaging (ME-NBI) and high-spatial-resolution MR provided further robust information in the diagnosis of EGC(33–36). Changes in the neutrophil-to-lymphocyte ratio (NLR) and the loss of fat and muscle after treatment had a high diagnostic accuracy for predicting the OS of patients(37, 38). These factors seemed to be sufficient for patient decision making. In summary, patients with noncurative ER should be reviewed in a timely manner through various methods and make the best decision to achieve longer survival times.
Our meta-analysis had some highlights as follows. Given the systematic searches and investigations of relevant data, more comprehensive articles that investigated the differences in the long-term survival rate between the additional surgery group and the observation group in patients with EGC after noncurative ER were included. Moreover, we performed subgroup analyses to discuss the influences of age on the long-term prognosis. Finally, we confirmed that additional surgery may be a better option among these patients.
Nevertheless, the limitations in this research cannot be ignored. First, the included studies were performed in the East. The results in the East may not be applicable to the West. More worldwide research was needed to verify the validity of the results. Second, all the included studies were retrospective studies and the differences were observed in the clinicopathological characteristics of the two groups, the results may be affected by potential bias. Finally, patients in the observation group did not undergo additional surgery for various reasons. The doctor's diagnosis and treatment plan tend to be largely affected by the patient’s willingness, advanced age, concomitant diseases and other factors. Selectivity bias may eventually lead to a poor long-term survival rate in the observation group.
In conclusion, this meta-analysis emphasized the evidences, increased the credibility of the outcomes that extra survival benefits exist with additional surgery among patients with EGC after noncurative ER and had clinical significance to guide patients to make the best treatment plan. This view also applied to the elderly. Although some elderly refused additional surgery for some reasons, timely follow-up should also be carried out for better prognosis.