Open Label International Multicentre Randomised Controlled Trial of Intensive Surveillance vs. Standard Postoperative Follow-up in Patients Undergoing Surgical Resection for Oesophageal and Gastric Cancer

It is an encouraging trend that the overall survival rate for oesophagogastric cancer has doubled over the last 20 years. For patients with locally advanced disease treated with curative intent, 5 year survival in the modern era approaches 50%. Relevant factors include earlier diagnosis, improvements in staging, and quality improvements in the standard modalities of surgery, chemotherapy and radiation therapy, increasingly delivered in high volume centers. When local or systemic failure occurs, where therapeutic nihilism may have once prevailed, a menu of therapeutic options can now be considered, such as immunotherapy, salvage locoregional surgery, resection of oligometastatic disease, brachytherapy, radiofrequency ablation (RFA) and stereotactic radiation therapy.

In the context of this changing landscape and expanded armamentarium, a key question, as yet unresolved, is how patients treated with curative intent should be optimally followed-up. The options include an intensive imaging surveillance approach using clinical assessment, cross-sectional imaging, and endoscopy, or one purely based on symptomatic follow-up to trigger further investigation.

The debate for oesophagogastric cancer is limited by a paucity of evidence. This may reflect both a lack of attention to this topic in research, with no RCTs, and relatively poor quality cohort and observational studies with considerable heterogeneity. The approach to surveillance varies considerably internationally. In Japan, a nationwide survey reported that that high intensity surveillance was common, with endoscopic surveillance utilized in over 80% of patients, in contrast to approximately 6% in Australia and New Zealand. In Europe, the European Registration of Cancer Care (EURECCA) Upper Gastrointestinal group reported a brief summary from 10 Centers, and highlighted substantial differences in elements of surveillance, in particular of cross-sectional imaging, which was sought in just 40% of patients. Guidelines also vary, for instance the European Society for Medical Oncology guidelines currently state, "With the exception of endoscopic or operative salvage after initial non-operative management, there is no evidence that regular follow-up has an impact on survival outcomes", while the UK NICE guidelines state, "for people without symptoms or evidence of residual disease after treatment for oesophagogastric cancer with curative intent, do not offer routine clinical follow-up or radiological surveillance solely for the detection of recurrent disease".

It is clear that research is urgently required on this important topic that will inform everyday practice and future guidelines. In this context, a European collaborative multicenter study was established with the primary objective of assessing the current situation in specialist centers internationally and its impact on survival and quality of life.

In this study, the investigators first surveyed 27 European centres, and identified marked variation in surveillance practices, with only 37% of centres providing routine radiologic surveillance for detection of recurrence, and only 19% undertaking routine surveillance endoscopy. The investigators then undertook a European multicentre cohort study, which included 4682 patients. At median follow-up 60 months, 47.5% developed recurrence, oligometastatic in 39%. Intensive surveillance, defined as a computed tomography scan undertaken at least annually for three years after surgery, was associated with reduced symptomatic recurrence and increased tumor-directed therapy. On multivariable analysis, no overall survival benefit was observed among all patients (HR1.01 [0.89-1.13]), but overall survival was improved following intensive surveillance for those who underwent surgery alone and those with lower pathological (y)pT stages. Intensive surveillance was associated with similar overall HRQL. This study established that there is widespread heterogeneity in surveillance protocols in Europe, and the vast majority of centres agreed there is a need for an RCT examining this issue.