Comparison between endoscopic treatment and surgery for elderly population with early gastric cancer

Objective Despite of the declining incidence of gastric cancer, the number of elder patients with gastric cancer is increasing because of aging society. The appropriate treatment strategies for elderly patients have not yet been well dened. The aim of this study is sought to evaluate short- and long-term outcomes after different therapies for early gastric cancers in elderly populations. We identied elderly patients aged ≥ 60 years with early gastric cancer (T1 stage) from the Surveillance, Epidemiology and End Results (SEER) database during1998 to 2010. We compared clinic features between different treatment groups and evaluated 1-year, 3-year and 5-year cancer-specic survival outcomes.


Conclusions
In elderly patients with early gastric cancer, short-and long term survival outcomes were similar between ET and the surgical groups, which indicated that endoscopic therapy is an appropriate and alternative approach for early gastric cancers in older western populations.

Background
Gastric cancer (GC) continues to be the fth most common cancers and one of the leading causes of cancer-related deaths in the world 1,2 . It is well acknowledged that early detection and treatment have reduced mortality of gastric cancer recently 3 . Due to improved endoscopic equipment and technique, the ratio of early gastric cancer (EGC) to total gastric cancer is increasing, especially in the Asia 4 . According to the World Health Statistics, there were dramatically growing number of older population worldwide as a result of aging society advancement 5,6 . Therefore, the number of elderly patients diagnosed with early gastric cancer is increasing 7,8 . Despite gastrectomy is still considered as the rst line treatment for EGC, the 5-year survival rate after surgery in elderly patients is worse compared with non-elderly population 9 . Recently, less-invasive techniques with resection, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have come to been widely accepted as a preferred therapeutic approach for EGC without lymph node metastasis, especially in the Asia 10-12 . The advantage of endoscopic treatment (ET) was minimally invasive in relation to the surgical treatment. Considering elderly patients with comorbid disease or poor general function 13 , ET might be better tolerated in elderly patients because of less-invasive nature of this modality. In the past decade, the number of elderly EGC patients undergoing ET was strikingly increasing. Although previous studies had assessed the outcomes of EGC after ESD or EMR in general patients from Asia, reliable evidence about appropriate therapeutic choices for elderly patients seemed still lacking, especially for the western population. Because of high incidence of gastric cancer in the Asia, the majority of previous data was based on the Asian population. Therefore, we aimed to performed a retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) cancer registry data to investigated the short and long term survival outcomes of ET or surgery in elderly patients with early gastric cancer.

Cohort population
Patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER)-a population-

Statistical Analysis
We compared the clinical characterises among treatment groups by Chi-square test. We adopted cancerspeci c survival as endpoint. Kaplan-Meier curves were generated to compare survival between treatment groups and the log-rank test was used to test the null hypothesis. The univariable and multivariable Cox proportional hazards regression analyses were used to calculate corresponding hazard ratios (HRs) and 95% con dence intervals (CIs) for treatment approaches and their association with survival time. Twosided P values at the P < 0.05 level was considered to be statistically signi cant. All analyses were performed with SPSS version 20.0 (SPSS, Chicago, Illinois, USA).

Baseline clinicopathologic characteristics
From the SEER database, we identi ed 5639 elderly patients (60 ≤ age ≤ 90) with early gastric cancer (T1) from 1998 to 2010 and nally included them in the study. Figure 1. displays the detailed stepwise cohort identi cation. Among those population, 2997 (53.1%) patients primarily underwent surgical resection and 328 (5.8%) patients underwent endoscopic treatment. Additional, the remaining 2314 (41.0%) patients who did not receive either ET or surgery. The mean follow-up duration was 3.5 years for patients. Baseline clinical characteristics for different treatment groups were showed in Table 1. Among patients received ET or surgery, there were no signi cant differences with respect to age, gender, tumour location. Patients undergoing ET were more likely to be married, diagnosis at recent year, well differentiated histology and T1a tumours, whereas patients who receiving surgery tended to have T1b tumour.

Short-and long-term outcomes
According to different treatment groups, elderly patients with T1 gastric cancer receiving neither surgery or ET were at higher risk of mortality compared with groups receiving either surgery or ET (Fig. 2)

Discussion
As the population ages, it is well anticipated that the number of elderly patients with early gastric cancer would continue to increase 6,14 . Although curative gastrectomy is a preferred treatment for early gastric cancer (EGC) 15 , a less invasive alternative, endoscopic treatment, is very attractive in this respect. While gastrectomy could provide adequate curative resection of EGC, it also caused higher risk of perioperative morbidities and gastrointestinal dysfunction as well as decreased quality of life [16][17][18] . Therefore, the optimal treatment strategy for elderly population is a challenge for gastroenterologists and raises great concerns. For elderly patients with some comorbidities, the less invasive treatment, endoscopic treatment, might be a more suitable approach compared to surgery 19 . According to previous studies, ET, either ESD or EMR had been proved as a feasible and safe technique for the early gastric cancer with appropriate indications [20][21][22] . Besides, it was reported that the clinical and survival outcomes of ET were not inferior to those of surgery, especially for ESD 23 . Therefore, it is reasonable to presume that ET was a safety and promising tool for EGC that ful lled certain indication criterion. At presently, however, limited studies directly compared survival outcomes of ET with those of surgery, especially for elderly patients. Chiu et al 16 . reported that similar oncological outcomes between ESD and radical gastrectomy in 144 patients with EGC. Compared with surgery group, ESD group had better perioperative outcomes, less complication rate, and hospital stay 16 . In another study by Park et al 23 . Outcomes of surgery and ESD were compared in 518 elderly patients with EGC and overall survival did not differ among two groups. In addition to limited patients' size, those population were all from Asia and the conclusion may not be applicable to Western patients. Therefore, large population-based studies from other regions need to be conducted.
In present study, we included 5639 patients to investigated the survival outcomes of different treatments in elderly patients with EGC. Among them, 2193 patients (52%) received either gastrectomy or endoscopic treatments. Gastrectomy was still the mainstay of treatment for older patients with EGC. However, no disease-speci c survival difference between ET and surgery groups was noticed in the current study. Furthermore, the similar disease-speci c survival rate at one, three and ve years after ET or surgery also indicated the effectiveness of ET. In Cox regression, tumour stage, grade, extension and year at diagnosis were also signi cantly associated with cancer-speci c mortality. Given the lack of detailed data in the SEER database regarding ET, this study could not identify whether it was performed by ESD or EMR. The results of this study appear to be in accordance with former studies. According to previous studies, ET, especial for ESD, had high resection rates with minimal associated adverse events 24 . Compared with surgery, the advantage of ET is maintaining general function of stomach and good quality of life after treatment. Therefore, for elderly patients, the less invasive treatment might be a preferred choice in consideration of the aforementioned complications for surgery.
Despite of a larger population-based study, our study still had some limitations that warrant further discussions. Firstly, this study was the retrospective analysis from a single country and obvious selection bias was inevitable according to the treatment modality. Secondly, the database did not include comorbidities, disease progression or recurrence, and details on endoscopic resection procedures. Despite these limitations, our study also provided some evidence about feasibility and validity of ET for elderly patients with EGC.
In conclusion, ET is a promising and safe therapy for elderly patients with EGC. Because of similar survival outcomes between the patients who undergo ET and surgery, ET could be considered as an initial treatment option for elderly patients, which might have implications for therapy decision making. More well-designed large clinical studies are further needed to con rm the utility of ESD among elderly patients with EGC.
Abbreviations ET, endoscopic treatment; EGC, early gastric cancer Declarations Ethics approval and consent to participate Approval from the ethical board was not required.

Consent for publication
Not applicable Availability of data and materials The datasets analysed during the current study are publicly available

Competing interests
The author discloses no con ict Detailed and stepwise selection owchart