Clinical management of gastric cancer: results of a multicentre survey

Despite the downward trend for cancer incidence and mortality in most countries, gastric cancer has become the second leading cause of cancer-related deaths worldwide with an annual rate of 700,000 deaths [1]. Almost two-thirds of the cases occur in developing countries, with 42% occurring in China alone, where gastric cancer remains the most deadly cancer among both sexes [2].

Surgical resection, chemotherapy and radiotherapy are mainstay of treatment for patients with gastric cancer [3‐5]. However, several questions concerning the treatment of gastric cancer remain. First, the type of resection and the role of extensive lymphadenectomy have been the subjects of international debate. Second, is there an ideal setting or regimen that predicts whether chemotherapy and/or radiotherapy should be provided before and/or after surgery as (neo) adjuvant treatment in patients with localized disease? Finally, there is no internationally accepted standard of care for patients with metastatic and advanced cancer, and uncertainty remains regarding the choice of the regimens [6, 7].

Clinical practice guidelines in oncology were developed to ensure quality cancer care throughout the world. Several global organizations have developed clinical practice guidelines for the treatment and management of gastric cancer. These groups include the National Comprehensive Cancer Network (NCCN) [8], the European Society of Clinical Organization [9], and the Japanese Gastric Cancer Association [10]. The NCCN gastric cancer guidelines (the Guidelines) have been widely used in China to reduce any disparities in treatment between different institutions for the treatment of patients with gastric cancer. However, we found in multidisciplinary team specialists from different department usually give different recommendations for surgery, neoadjuvant, adjuvant, and advanced treatment planning for patients. Until now no studies have been carried out in regard to variations of the clinical management of gastric cancer. Accordingly, the aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the Guidelines.

Quality cancer care depends on research findings, treatment improvements, and practice guidelines. Clinical guidelines have been designed to maximize the effectiveness of care as an important tool in evidence based practice, may reduce inappropriate variations in treatment approaches, and allow for continuous monitoring of appropriate care delivery. However, the practice guidelines are wasted unless they are used in everyday practice by clinical oncologists [12‐14]. In this study, we found considerable variation when comparing the recommendations of the Guidelines and routine practice of different oncology specialists.

In recent years, a series of studies in various cancers demonstrated that multidisciplinary care could achieve greater resource efficiency and improve standards of care through a reduction in duplication and gaps in service provision, enabling the delivery of holistic services and better continuity of care [15]. Effective multidisciplinary team functioning is important not only for the benefit of patients, but also for the efficiency, morale, and work satisfaction of the individual team members [16]. Multidisciplinary care has become the standard in cancer management, which is supported by national and international clinical practice guidelines in many countries [17]. The management of gastric cancer usually requires the expertise of several disciplines, including surgical oncology, radiation oncology, medical oncology, nutritional support, and endoscopic expertise. The Guidelines encourage a multidisciplinary evaluation for the treatment of patients with gastric cancer [8]. However, approximately 90% of the participants of our survey reported that less than half of all patients received multidisciplinary evaluation before treatment. Through stratification analysis, we found that there was no difference between participants from university hospitals and those from general hospitals, but participants with a short time in practice (5-15 y) were more likely to have their patients to receive multidisciplinary evaluation. Perhaps experienced clinicians are more confident in making treatment decisions alone.

The type of resection and the role of extensive lymphadenectomy have been the subject of debate according to the Guidelines [8]. In this study, D2 dissection was generally considered as an essential procedure, however, surgical oncologists have different ideas as to the surgical procedure of choice for gastric cancer, such as the gastrectomy options for proximal gastric cancer, the extent of the lymph nodes dissection, and what is an adequate surgical margin. There are more controversial issues with regards to the treatment principles among medical oncologists and radiation oncologists, with many of them unfamiliar with the principals of surgery. In addition, the participants provided different selections for questions on the adjuvant, neoadjuvant, and advanced settings, compared to the Guidelines.

A number of factors are considered during the process of formulating a treatment plan for gastric cancer patients: Most importantly, how well a clinician adheres to the practice guidelines depends largely on the strength of the evidence supporting clinical practice. If a clinician finds that the evidence is scant or if the evidence is not suitable for their patients, then they could not adhere to the guidelines. We have found evidence to support this issue in this study. For example, the role of adjuvant therapy for gastric cancer has been controversial given the lack of high level, worldwide evidence. Although numerous phase III studies, including a surgery-only group, have been reported in the last three decades, definitive evidence of the efficacy of postoperative chemotherapy is lacking [18]. The first positive, large scale phase III trial by the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) group reported the superiority of S-1 as an adjuvant chemotherapy over surgery alone after D2 lymph node dissection in a Japanese population [19]. The effect of adjuvant chemotherapy outside of East Asia is uncertain, and standard management following curative surgery is heterogeneous throughout the world [18]. Recent meta-analyses have suggested a small benefit of adjuvant therapy, but the widely varying regimens and populations from the studies included in these meta-analyses have limited their impact [6, 7, 18, 20, 21]. In addition, the landmark trial in chemoradiation cited in the Guidelines was the intergroup trial INT-0116 [22]. However, 90% of the patients enrolled in this study received D0 (54%) or D1 (36%) dissection, while D2 dissection is widely performed in China. It is estimated that the radiation in INT-0116 makes up for the inadequacy of surgery. Again, intraperitoneal chemotherapy was widely accepted by the participants in this study while it was not addressed in the Guidelines at all. This may be explained by the geographical variation in standard practice, which really exists. For instance, adjuvant oral fluoropyrimidine monotherapy following radical D2 resection is the standard care of stage II-III gastric cancer in Japan. In Europe, combination chemotherapy delivered before and after D2 resection is the most widely accepted practice, and in the USA, patients will routinely be referred for adjuvant chemoradiation following resection [23]. There is no worldwide, high-level evidence on the treatment of gastric cancer, hence, it can be expected that clinicians do not adhere to the Guidelines. Secondly, some of this variation appears to represent professional preferences. Recent studies have shown that perioperative chemotherapy yields a substantial pathologic response that result in durable survival time [24]. The British Medical Research Council performed the first well-powered phase III trial (MAGIC trial) for perioperative chemotherapy [25]. The result has established perioperative chemotherapy as an option for the standard of care of patients with resectable gastric cancer, according to the Guidelines [8]. In our study, there were few surgical oncologists who preferred neoadjuvant chemotherapy. Finally, a lack of consistency among clinicians may also be the result of recognition error and unfamiliarity with the use of accepted criteria. In this study, a few medical oncologists and radiation oncologists were not clear about the surgical principle behind treating gastric cancer. In addition, the rapid dissemination of new knowledge makes it more difficult for clinicians to keep up to date, and inconsistent reports in the literature can also contribute to variability in treatment decision making among clinicians.

We acknowledge there are several limitations to the current analysis. Firstly, we asked participants to answer based on what they "usually do with most" of their patients. However, respondents were more likely to select "one best answer". Their answer may be different from their actual decision-making in the oncology clinic. The second limitation is that we did not elaborate further on many of our findings due to our concern about the length of the survey and ensuring responders' anonymity. For example, we did not collect data about institutional affiliations to explore whether practice was consistent within the same division. Thirdly, we did not perform multivariate analyses for each clinical scenario to analyze differences according to the type of practice (university vs. other), age, gender, experiences of participants, and volume of a center, etc. However, these factors could also affect the clinician's practice. For example, it was reported that surgeons who do more gastric resections per year were more likely to report performing a D2 resection, according to a study in Canada [26]. In addition, it is unclear whether the area of specialty (surgery vs. medical) affects the treatment option. We could not determine from the current study how a surgeon affects the choices of a chemotherapy regimen or how a medical oncologist affects the type of resection. Finally, and perhaps most importantly, several of the scenarios chosen were purposefully controversial without clear evidence to suggest one optimal approach.

Nevertheless, we believe that the practice variation documented here should encourage the planning and implementation of randomized clinical trials to address controversial areas of the treatment of gastric cancer. The significant increase in the quantity of scientific clinical trials should result in guidelines updated with more certainty and supporting evidence. This survey should also encourage specialists in the field of gastric cancer to keep up to date with new knowledge with a focus on the use of accepted treatment criteria. More continuing medical education programs should be designed to shorten the knowledge gap and improve the quality of care and outcome of multidisciplinary management. The documentation of practice variation highlights areas where better education, dissemination of information, and quality improvement systems can improve care, as long as the evidence for a practice has also increased with additional studies.

These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines. The study should encourage the planning and implementation of randomized clinical trials to address controversial areas of the treatment of gastric cancer and to establish updated guidelines with more certainty and supporting evidence. It should also encourage the development of more continuing medical education programs designed to shorten the knowledge gap and to improve the quality of care and outcome of multidisciplinary management. Specialists in the field of gastric cancer should keep up to date with new knowledge with a focus on the use of accepted treatment criteria.