Real-World Compliance of Surgical Treatment According to the Korean Gastric Cancer Guideline 2018: Evaluation From the Nationwide Survey Data 2019 in Korea

Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related deaths [1, 2]. However, the incidence of gastric cancer is gradually decreasing worldwide, particularly in northeastern Asia [2, 3]. This might result from efforts to conduct studies to improve treatment outcomes worldwide and perform screening programs in highly prevalent areas. Gastric cancer guidelines have been published in several countries, with evidence levels and recommendation grading determined by clinical data and the specific medical context in each respective nation [4]. The evidence and recommendations were based on a systematic literature review, including prospective multicenter randomized trials and other retrospective studies.

Compliance with gastric cancer treatment guidelines is relatively low, and survival is impaired in non-compliant patients in the Western world [5, 6, 7]; however, this is not limited to gastric cancer. The survival rate for many cancers, including ovarian and pancreatic cancers, is significantly lower in patients who do not adhere to these guidelines [8, 9]. Moreover, studies have shown differences in survival based on compliance with National Comprehensive Cancer Network (NCCN) guidelines at the patient, regional, and hospital levels in patients with gastric cancer [10,11]. Adherence to the NCCN guidelines differed by region and hospital, and the results were significantly related to survival.

However, such data are not available for Eastern countries. Korea, Japan, and China have their own guidelines; however, no studies have investigated compliance with these guidelines in Eastern countries [12-14]. Evidence-based Korean practice guidelines for gastric cancer were published in 2018 by a panel of clinical experts [12]. Since 1995, a nationwide survey has been conducted every 5 years by the Korean Gastric Cancer Association for patients surgically treated for gastric cancer in Korea. Survey data were collected in 2014 and 2019, before and immediately after the 2018 guidelines were published [15, 16].

This study evaluated real-world compliance with surgical treatment according to Korea's gastric cancer treatment guidelines. In addition, compliance before and after the publication of the guidelines was compared.

In our study, overall compliance to guideline was over 80% in all aspects of the 2019 and 2014, before and after the 2018 guidelines in Korea. In addition, there was no significant difference in the overall compliance rate based on regional data. Compared with previously reported compliance rates in Western countries, the compliance rate in Korea is quite high. Because the recommendation guidelines were based on evidence of improved survival, one of the critical factors for the high cure rate of gastric cancer in Korea may be the high compliance rate with the recommendations in the guidelines and the national screening program [17]. So far, this study is the first report concerning compliance with guidelines in Eastern countries in the literature.

According to the results of a study analyzing guideline compliance between 2004 and 2014 in patients with gastric cancer based on the NCCN guidelines, only 36.5% of stage 0/I and 41.8% of stage II/III patients met the minimum standard of at least 16 lymph nodes examined and R0 resection [7]. In that study, guideline adherence was defined as satisfying 5 operative standards, including gastric resection extent, surgical method, and LND. However, it is a looser definition than that used in our study. Another study investigating NCCN guideline adherence based on data from 2004 to 2015 in patients with gastric cancer reported that only 32% followed the guidelines [10]. In this study, guideline adherence was satisfied if only one of the NCCN guidelines was followed. In both studies, the survival rate was low in the nonadherent patient group.

Compared with the 2019 data, the overall compliance rate in 2014 was similar regarding the extent of gastric resection (83% and 89%, respectively). Several inferences can be made regarding why 2014 was slightly higher than 2019 before the publication of the guidelines. In the subgroup analysis, the majority of noncompliance was when the DG was in the upper third portion. Guidelines recommend TG or PG in the upper third portion; however, this bias may occur because surgeons prefer near-TG to TG when it is possible to preserve the stomach, even if the remnant stomach is very small. Most surgeons prefer DG because it is technically easier [18, 19]. Second, the number of surgical options, such as PG and PPG, increased in 2019 (4.5%) compared with 2014 (2.6%) as clinical interest in function-preserving surgery increased. In the recently updated 2022 guidelines, the recommendations to decide whether to perform TG or DG change depending on whether the fundus should be preserved [20].

Compared with 2014, the compliance rate was similar in 2019, both before and after the guidelines were published. In 2010, a study comparing guideline adherence before and after guidelines was published in the Netherlands (6). In this study, the overall compliance was relatively low (42.5%–78.0%); differences before and after publication of the guidelines did not show significant changes, and they concluded that the recommendations were already well implemented. In Korea, the difference before and after the implementation of the guidelines was not large; however, the relatively high compliance rate indicates that appropriate treatment has been administered. Among the data investigated in the 2019 and 2014 national surveys, we evaluated the changes in compliance related to LND, adjuvant chemotherapy, and splenectomy, which were not surveyed in 2014.

The 2018 guideline included two "not recommended" negative recommendations. The first procedure was splenectomy. Among patients with pStage IB, II, and III disease, splenectomy was performed in 2.63% of all patients, representing 8.08% of the patients who underwent TG. However, the exact reason for splenectomy for therapeutic or prophylactic LND or other purposes is unknown. Second, gastrectomy in pStage IV patients was performed in 48.66% in 2019 and 54.53% in 2014. However, based on national survey data, the exact cause of noncompliant surgeries was not identified for curative intent or palliation of symptoms in stage IV. Therefore, the actual noncompliance rate may be lower than the survey data.

In 2019, 1.51% of patients with pStage I gastric cancer received adjuvant chemotherapy, whereas 24.82% of patients with stage II or III did not receive adjuvant chemotherapy. However, the cause of noncompliance to adjuvant chemotherapy has not yet been identified. Some guidelines recommend that adjuvant chemotherapy be considered even in pStage I if patients have high-risk factors [21]; however, observation is recommended in the 2018 [12] and 2022 revised Korean guidelines [20]. Among the 997 patients who did not receive adjuvant chemotherapy in stages II and III, 585 (58.67%) were stage II, and 412 (41.32%) were stage III. The survey did not identify why patients did not receive adjuvant chemotherapy. However, it was assumed that old age, poor general condition, and lack of follow-up were the frequent causes in the real world. Some studies also recommend adjuvant chemotherapy for elderly patients, considering their general condition [22]. However, the benefits of adjuvant chemotherapy in elderly patients remain controversial [23]. Based on the age difference between patients compliant and non-compliant with adjuvant chemotherapy, age was probably the most significant reason adjuvant chemotherapy was not administered. Data on adjuvant chemotherapy were not surveyed in 2014, and a comparison was not performed.

Although the efficacy of preoperative chemotherapy remains controversial, research on this topic is actively progressing. In 2019, 587 of 14,077 patients received preoperative chemotherapy. A total of 489 patients underwent neoadjuvant chemotherapy, and 98 patients underwent conversion surgery after palliative chemotherapy. According to the 2018 Korean guidelines, neoadjuvant chemotherapy for potentially resectable gastric cancer is inconclusive if D2 LND is considered. [12]. However, neoadjuvant chemotherapy is conditionally recommended in the 2022 Korean guidelines as part of the perioperative chemotherapy for patients with resectable locally advanced gastric cancer. Conversion surgery is recommended for patients with stage IV gastric cancer [20]. As long as the guidelines are updated, changes in compliance must be evaluated.

In our study, the number of surgical cases differed according to region of origin. More than half of the surgeries were performed in Seoul and surrounding metropolitan areas. In contrast, only 1.16% of surgeries were executed in remote areas of Seoul. Nevertheless, there was no significant difference in the regional compliance rate, which implies that gastric cancer treatment is well-standardized nationwide in Korea, except for the rate of gastrectomy in stage IV patients. Regional differences exist; however, the exact reason for gastrectomy is unknown. Disparities in cancer treatment by region have been studied not only for gastric cancer but also for pancreatic, breast, lung, and colorectal cancers [11, 24, 22, 23, 27]. All these studies were conducted in the United States, and there were regional differences in treatment methods for all types of cancer except breast cancer, which has been reported to be significantly associated with improved survival. One study compared adherence to the NCCN gastric cancer guidelines by region, and the median 2-year overall survival varied significantly by region [11].

Gastric cancer guidelines in each country show little difference but are based on studies that have proven to improve survival [4]. In addition, studies have demonstrated that a high guideline compliance rate improves survival [7, 28]. According to a 2020 study on primary gastric cancer, the incidence rate in Korea was the third highest; however, its mortality rate was the lowest among 185 countries [29]. One reason for this may be the high rate of early gastric cancer due to its early detection through national screening endoscopy [30], and another reason may be that compliance with guidelines is higher than that in other countries.

This study has some limitations. First, this study included patients who underwent surgery for gastric cancer but did not include all patients who received endoscopic treatment or systemic therapy. Second, the collected data included pathological rather than clinical stages. Therapeutic strategies are typically based on clinical staging. Therefore, the intended surgical method may differ because of the discrepancy between clinical and pStages. Third, there were no data related to survival, thus proving the effectiveness of these guidelines. Fourth, the exact reason for noncompliance was not identified, which might include several clinical trials that enrolled patients or other causes. These data included patients enrolled in several prospective studies conducted during data collection. These clinical trials may have affected the compliance rates regarding the extent of gastric resection or LND. Therefore, further studies on guideline compliance are required to collect more data and analyze survival.

In conclusion, real-world compliance with gastric cancer treatment guidelines is quite high in Korea compared with other countries. Additionally, there were no significant regional differences in compliance regarding the extent of gastric resection, LND, surgical approach, or adjuvant chemotherapy.