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Variations among 5 European countries for curative treatment of resectable oesophageal and gastric cancer: A survey from the EURECCA Upper GI Group (EUropean REgistration of Cancer CAre)
European Journal of Surgical Oncology (EJSO), In Press, Corrected Proof, Available online 30 September 2015, Available online 30 September 2015
EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe.
Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included.
United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%.
This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.
Keywords: EURECCA, Oesophageal cancer, Gastric cancer, International audit, Outcomes.
Overall survival for patients with gastric and oesophageal cancer has shown little improvement over the last 20 years. For gastric cancer the recent EUROCARE-5 study has shown a slight improvement in 5-year survival from 23.3% in 1999–2001 to 25.1% in 2005–2007. This study also highlighted significant geographical differences across Europe with highest survival in southern and central Europe and lowest survival in Eastern Europe, the UK and Ireland. The overall 5-year survival for oesophageal cancer also remains poor at 12%. The main reason for the poor outcome is the late stage at diagnosis for both cancer sites. However, geographical differences may reflect differences in patterns of treatment.
Most population-based studies provide a broad overview, but may lack more detailed information on staging and treatment necessary to intervene and improve patterns of care. Prospective cancer audits maintained in real-time provide very valuable tools for improvement as it happens. Dikken et al. combined information from four countries using either national registry data or national audit outcomes. Although the databases were not complete, reflecting intra-country variations in data recording, there were considerable variations in treatment practices and outcomes particularly for surgical resection rates and postoperative mortality. This study highlighted the need to develop a much larger collaborative approach to be able to compare and contrast current approaches to oesophageal and gastric cancer and search for the best care for this specific patient group.
In colorectal cancer, the EURECCA initiative has demonstrated how to establish an audit across European countries. Following this model the EURECCA Upper GI project was established and a common dataset was developed using existing data items recorded in 7 countries. This study reports the results of comparison of these data items in the initial 5 countries collaborating in the project.
Materials and methods
Five countries (Netherlands, France, Spain, UK and Ireland) have collected data on patients with oesophageal and gastric cancer treated with curative intent over a 1-year period (2011–2012). Inclusion criteria were patients with SCC and ACA of the oesophagus, oesophago-gastric junction and stomach who underwent curative treatment including surgery. Each country submitted data using a dataset of 46 items identified as common to all data sources. Briefly, this dataset involved collection of existing datasets and identified those items, which were commonly recorded.
The uniform systematic list of data included: patient demographics, stage of the tumour at diagnosis, treatment strategies, operation outcomes, and histological results.
The sources of data varied between the countries and included national registries, established national audits and audits by large collaborative groups.
The Netherlands started the Dutch Upper GI Cancer Audit in 2011 (DUCA). DUCA is nationwide and covers all centres performing oesophageal and gastric surgery. It includes patients with primary disease (stages I to IV) and recurrent cancers. DUCA records surgery with both palliative and curative intent, as well as for prophylaxis. During the study period there were 25 hospitals treating oesophageal cancer and 42 treating gastric cancer. The number of patients in DUCA in 2012 represents 91% and 82% respectively of all cases recorded by the Dutch National Cancer Registry.
Data from France are presented from the FREGAT working group. This represents a collaborative group of 19 centres in France recording information on retrospective databases. Data for gastric cancer has been collected since 2009 and for oesophageal cancer since 2010. The current sample includes patients treated from January 2010 until December 2012.
The Spanish oesophageal-gastric cancer project is a regional project based on the 7.5 million population in Catalonia including 20 Catalan hospitals. During the study period, consecutive cases were included, with data provided by the surgeons of the participating hospitals.
The UK National Oesophago-Gastric Cancer Audit (NOGCA), established in 2006, was designed to collect prospective data on patients diagnosed with invasive epithelial cancer of the oesophagus, gastro-oesophageal junction or stomach. NOGCA began its second audit in 2011 and by the end of the first year, clinical data had been submitted by 154 (99%) of 159 English NHS organizations that provide oesophageal and gastric cancer care and by all Welsh acute NHS Trusts – 42 of these undertake all of the resections. Data was submitted on over 11.000 patients with an overall case ascertainment for diagnosed cases of 83% and of 89% for resected cases. The data for this survey included the 12 months from April 1st 2011 to March 31st 2012.
For Ireland the data reflects common data provided by the 4 designated oesophageal and gastric cancer centers to the National Cancer Control Program (NCCP). The total number of hospitals undertaking oesophageal and gastric cancer surgery was reduced from 11 to 4 between 2005 and 2011.
Several countries commenced their registries and audits in 2011 and data validation has not been possible. As a result, it is likely that data are not complete particularly for case ascertainment. Conclusions based on the numbers are therefore limited and these should be considered merely illustrative.
Patient and tumour characteristics were assessed according to country and stratified according to oesophageal, junctional, or gastric location. Differences in distribution between countries were tested using the chi-square test or Fisher's exact test where one of the expected values was less than 5. Treatment was stratified according to neoadjuvant treatment, surgery and adjuvant treatment for the different locations and differences in distribution between countries were tested with chi-square or Fisher's exact, where appropriate with p < 0.05 as level of significance. For patients who underwent resection, pathology results were compared between the countries with the same tests. In-hospital and 30-day mortality were depicted according to oesophageal or gastric cancer. STATA/SE version 12.0 was used for statistical analyses.
During the 12 months period, 4668 cases have been recorded across the 5 countries, 2666 oesophageal and GOJ (gastro-oesophageal junction) tumours and 2002 gastric cancers ( Table 1 ). The majority of these were planned for resection although a small number from the Netherlands and Ireland planned for non-surgical treatments have been included. The proportion of oesophageal and junctional cancers predominated in all countries except Spain where there were more gastric cancers.
a For The Netherlands, these numbers also include 72 patients for whom a curative resection was not planned.
b For Spain TNM stage was detailed as T and N+/− stages, not as TNM stage, therefore, this corresponds to an extrapolation of T stage (for information, for Spain 65.2% of oesophageal cancers had positive nodes on initial staging, and 46.7% of gastric cancers).
c For Ireland, these numbers also include 68 oesophageal cases treated with definitive chemotherapy.
GOJ = Gastroesophageal junction, ASA = American Society of Anaesthesiologists.
The majority were male patients with a greater proportion of men with oesophageal and junctional cancers than with gastric cancers. Those with gastric cancer tended to be older and were overall less fit with higher ASA (American Society of Anesthesiologists) scores except in France where there was a tendency for a younger population who were fitter. In oesophageal and junctional cancers the proportion of ACA predominated in all countries except France where the proportion of ACA and SCC was almost equally distributed.
Most oesophageal tumours were located in the distal third or at the GOJ except in France where the proportions were similar for middle and lower third tumours. Most gastric cancers were located in the mid body or the distal stomach except in the UK where there were higher rates of proximal cancers.
Preoperative clinical TNM stage (cTNM 7th edition) was based on standard staging investigations including endoscopy, endoscopic ultrasound (EUS), multi detector computed tomography (MDCT) and laparoscopy and PET-CT scanning where indicated.5 and 6 The stage distribution showed marked variation with more patients in France and Ireland with earlier stage disease in all three tumour sites compared with the other three countries.
Data on 4541 patients planned for curative resection has been analysed for each country ( Table 2 ). The use of neoadjuvant and adjuvant therapies varied across the five countries. Most patients in the Netherlands and Ireland received neoadjuvant treatment for oesophageal and junctional cancers. This was less frequently seen in Spain, France, and the UK respectively. The biggest differences were in the use of neoadjuvant chemotherapy and chemoradiotherapy in oesophageal and junctional cancers. In the UK, perioperative chemotherapy was predominantly used contrasting with the Netherlands and Ireland where neoadjuvant chemoradiotherapy was the main modality. In gastric cancer, neoadjuvant chemotherapy was more consistently used although only about 1 in 3 patients received this treatment.
a For the Netherlands, proximal and distal gastrectomy were identified together as partial gastrectomy. Besides, 72 patients for whom curative resection was not planned were excluded in this table.
b For Ireland, the 68 oesophageal cases treated with definitive chemotherapy were excluded for this table.
The use of adjuvant chemotherapy was probably linked to neoadjuvant treatment as a perioperative approach; the data however does not allow that to be confirmed. There were greater proportions of patients in the UK, France and Spain receiving the postoperative component of their perioperative treatment. In gastric cancer, there were similar rates across the five countries.
The surgical approaches for resection of oesophageal or GOJ tumours showed marked variation. The transthoracic approach was commonly practiced for oesophageal cancer in the UK and France whereas in the Netherlands and Ireland. 2/3 of cases were transthoracic and 1/3 was transhiatal. In France and the Netherlands, transthoracic and transhiatal approaches were used for GOJ cancers compared with extended total gastrectomy which was commonly undertaken in Spain.
In gastric cancer, subtotal and total gastrectomy were performed with equivalent frequency overall. However in Spain subtotal gastrectomy was the more common procedure, and total gastrectomy predominated in France.
Information on outcome was available for 4422 patients. Thirty day and in hospital mortality rates were similar for oesophagectomy and gastrectomy ( Fig. 1 ). In the Netherlands and Spain mortality rates were higher after gastrectomy than after oesophagectomy. For oesophagectomy, 30 day and in hospital mortality rate ranged from 1.7% (UK) to 6.3% (France), and from 2.9% (UK) to 5.3% (Spain). For gastrectomy, 30 day and in hospital mortality rate ranged from 1.0% (UK) to 6.8% (Spain), and from 2.2% (UK) to 7.2% (Spain).
The pathological tumour stage showed similar proportions of both early (stage I and II) and advanced (stage III and IV) oesophageal and junctional cancers across the five countries ( Table 3 ), although there was a greater rate of stage IV cancers in Spain.
a For Spain TNM stage was detailed as T and N+/− stages, not as TNM stage, therefore, this corresponds to an extrapolation of T stage (for information, for Spain 42.6% of oesophageal cancers had positive nodes on initial staging, and 54.6% of gastric cancers).
In gastric cancer there was a wide variation in stage I and in situ disease with 22% in the Netherlands compared with 40% in France. There were proportionately more stage IV gastric cancers in Spain and the UK compared to the other countries.
Assessment of the quality of the surgery evaluated the rates of R0 resection and the rates of nodal retrieval. For oesophageal and GOJ tumours, the mean R0 rate was 86.4% (70% UK; 85% Ireland; 91% the Netherlands; 91% France and 95% Spain), and the mean proportion of specimens with 10 or more lymph nodes retrieved was 85.8% (77% France; 83% Spain, 84% the Netherlands; 90% UK and 95% Ireland).
For gastric tumours, the mean R0 rate was 88.4% (80% UK, 88% France, 89% the Netherlands, 90% Spain and 95% Ireland), and the mean proportion of specimens with 10 or more lymph nodes retrieved was 87.8% (82% the Netherlands, 89% Spain, 85% UK, 91% Ireland and 92% France).
The aim of the EURECCA project is to improve the quality and reduce the variation of cancer care by data registration, feedback, forming plans for improvement and sharing knowledge of performance and science. This study is the first, descriptive comparison of current practice in the management of oesophageal and gastric cancer in a number of European countries. It reflects activity in a recent period (2011–12) and demonstrates how a collaborative international project can be established effectively. The description of the common dataset has allowed equivalent data to be collected and compared. Uniquely, this survey includes more cancer management data items in detail than standard outcome data such as incidence, mortality and survival.
A limitation of the approach in this study has been the different sources of information available per country. Combining data from countries with national registries and audits with information from large collaborative groups may provide an incomplete picture because of incomplete recording and also may not be representative of the whole country. Outcome comparison is therefore limited but it does allow evaluation of the shared dataset approach which will be instructive for future international comparisons. The commitment of the leads for each country has ensured a high level of engagement with their colleagues, which may obviate some of the limitations of completeness and representative findings. It is hoped that this first survey of the care for patients with oesophageal and gastric cancer will generate a positive stimulus to encourage data collection internationally.
There are a number of observations that need further investigation before expansion of the project to other countries. Looking at the characteristics of the patients in the different countries, several points need to be substantiated further. There are epidemiological differences between the five countries that are known from previous studies particularly in terms of tumour stage in gastric cancer. The age of patients undergoing treatment varies between the countries that might stimulate other countries to reconsider how they treat the elderly patient with cancer.
This study illustrates that European countries have different practices with respect to radical therapies. Despite the large volume of well-designed clinical trials showing a benefit of preoperative therapies, there are a large number of patients who have been treated by surgery alone. In future prospective registries this will need to be evaluated in more detail. Nevertheless, it is of concern because patients may not be considered for what in many countries is considered as standard of care. There are significant differences in the use of perioperative therapies with more chemoradiotherapy used in the Netherlands and Ireland compared to the UK and France. This is likely to reflect the influence on national guidelines and patterns of care of national randomized controlled studies such as CROSS in the Netherlands and OEO2 in the UK.
The same observation could be applied for the differences in surgical approaches in both oesophageal and gastric cancer. The proportion of transthoracic and transhiatal resections for oesophageal and junctional cancer in the Netherlands is likely to reflect the outcome of the comparative trial from Hulscher et al. However there are differences in the use of extended gastrectomy for junctional cancers, particularly in Spain, which may be related to the pattern of disease presentation.
Future studies will be able to assess any effect of these variations on survival. The immediate outcome measures of operative and in hospital mortality show some variability and are different from published data in case series and randomized trials. The nature of observational population-based international comparisons is likely to be more representative of standard practice as opposed to the selection bias of institutional series and trials. Overall, the mortality in the UK tends to be lower than the other countries and this may reflect the centralization policy in the UK introduced in 2002 restricting surgery to centers covering at least 1 million population.
There is an interesting observation in the discrepancy between clinical stage and postoperative pathological stage, which is consistent across all countries. There appears to be an effective downstaging when comparing clinical and pathological stage. Although this may reflect an effect of preoperative chemotherapy or chemoradiotherapy, this may also reflect the limitations in accuracy of preoperative staging. In addition there is variation in the R0/R1 rates following oesophagectomy, which may be accounted for as countries have different definitions for involvement of the circumferential margin. This needs to be considered further as there may be a case for standardizing staging assessment pretreatment.
This study has reported a collaborative approach by five European countries and has demonstrated both common themes and variation in practice. Although the study has its limitations, it has confirmed that such a process can be established, does demonstrate the current approach to the management and treatment of oesophageal and gastric cancer, and suggests areas for future investigation. The EUROCARE-5 study has reported marked variation in survival across Europe and using data such as in this study is likely to identify how this variation can be further understood. It is intended to develop this project further by increasing the number of countries taking part, repeating the audit using a common dataset to assess consistency and to evaluate the pattern of service provision across the different countries. In this way, standards of care may be determined which can enhance more collaborative work, and attempt to explain and resolve why some countries have better outcomes than others.
Conflict of interest
The authors declare no conflict of interest.
The 2013 Annual Grant for international mobility from the AFC (French Association of Surgery) was part of the salary of MM.
The authors would like to thank all the participating countries and participants of the EURECCA Upper GI Group for their input and providing the results from the 10th International Gastric Cancer Congress (IGCC) presentations, in Verona, Italy, and the organizing committee of the 10th IGCC congress. The authors would also like to thank. Georgina Chadwick and Oliver Groene from the UK National OG Cancer Audit for their help.
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a Department of Surgery, Royal Marsden NHS Foundation Trust, London, United Kingdom
b Department of Digestive and Oncological Surgery, C Huriez University Hospital, Lille, France
c Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
d Department of Surgery, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands
e Department of Surgery, St James's Hospital and Trinity College, Dublin, Ireland
f Section of Gastrointestinal Surgery, Hospital Universitario del Mar, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
g Department of Surgery, Addenbrookes Hospital, Cambridge, United Kingdom
∗ Corresponding author. Department of Surgery, Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, United Kingdom.
© 2015 Published by Elsevier B.V.