Presented to the Annual Meeting of the Dutch Surgical Society, Veldhoven, the Netherlands, May 2012, and the European Society of Surgical Oncology 32nd Congress, Valencia, Spain, September 2012; published in abstract form as Eur J Surg Oncol 2012; 38: 765
In several European countries, centralization of oesophagogastric cancer surgery has been realized and clinical audits initiated. The present study was designed to evaluate differences in resection rates, outcomes and annual hospital volumes between these countries, and to analyse the relationship between hospital volume and outcomes.
National data were obtained from cancer registries or clinical audits in the Netherlands, Sweden, Denmark and England. Differences in outcomes were analysed between countries and between hospital volume categories, adjusting for available case-mix factors.
Between 2004 and 2009, 10 854 oesophagectomies and 9010 gastrectomies were registered. Resection rates in England were 18·2 and 21·6 per cent for oesophageal and gastric cancer respectively, compared with 28·5–29·9 and 41·4–41·9 per cent in the Netherlands and Denmark (P < 0·001). The adjusted 30-day mortality rate after oesophagectomy was lowest in Sweden (1·9 per cent). After gastrectomy, the adjusted 30-day mortality rate was significantly higher in the Netherlands (6·9 per cent) than in Sweden (3·5 per cent; P = 0·017) and Denmark (4·3 per cent; P = 0·029). Increasing hospital volume was associated with a lower 30-day mortality rate after oesophagectomy (odds ratio 0·55 (95 per cent confidence interval 0·42 to 0·72) for at least 41 versus 1–10 procedures per year) and gastrectomy (odds ratio 0·64 (0·41 to 0·99) for at least 21 versus 1–10 procedures per year).
Quality assurance is increasingly being acknowledged as a crucial factor for improvement of care for patients with oesophageal and gastric cancer. In Europe, the average 5-year survival rate is 11 per cent for oesophageal cancer and 25 per cent for gastric cancer, but variation between and within countries is considerable1. The reasons for these variations are difficult to assess. In some countries there are nationally sponsored cancer registries, whereas others have established clinical audits. Data recorded are variable and there are differences in data interpretation. Outcome comparisons are inevitably limited. One of the key elements in any comparison is data completeness, in order to minimize bias.
Programmes and processes have been established in the Netherlands, Sweden, Denmark and England that are designed to achieve as comprehensive data collection as possible with the aim of assuring the quality of treatment of oesophageal and gastric cancer. The present study was undertaken to evaluate differences in annual hospital volumes, resection rates and treatment outcomes in these four countries, and to determine where improvements can be made to allow better comparisons between countries.
National data were obtained from cancer registries in the Netherlands and England, and from clinical audits in Sweden and Denmark (Table1). The cancer registries from the Netherlands and England, and the audit from Denmark, provided national coverage of all patients with a diagnosis of oesophagogastric cancer. Only patients who underwent surgery were included in the Swedish audit, and so no resection rates could be calculated for Sweden. In several Swedish regions, it was apparent that not all patients who had undergone surgical resection had been registered. To reduce the chance of selection bias, only Swedish regions with a case ascertainment above 90 per cent were included. Applying the same criteria, detailed data from patients in the voluntary UK National Oesophago-Gastric Cancer Audit (NOGCA)3 were not included (case ascertainment 71 per cent).
Table 1. Characteristics of participating countries and available data sets
Case ascertainment was incomplete in certain regions in Sweden; regions with case ascertainment below 90 per cent were excluded. +, Yes; − , no. ASA, American Society of Anesthesiologists; O, oesophageal; OGJ, oesophagogastric junction; S, stomach; A, adenocarcinoma; SCC, squamous cell carcinoma; TNM, tumour node metastasis.
Resection rates were calculated in the cohort of patients with a diagnosis of oesophageal or gastric cancer between 2004 and 2009. Postoperative mortality, survival and annual hospital volumes were calculated in the cohort of patients who underwent surgical resection between 2004 and 2009.
Demographic information was available in all data sets, but co-morbidities were not registered uniformly and could therefore not be used for case-mix adjustments. Tumour location and histology based on the International Classification of Diseases for Oncology (ICD-O) were available in all data sets4. Tumour location was defined as oesophagus (ICD-O C15.0–16.0) or stomach (ICD-O C16.1–16.9). Staging was performed according to the sixth edition of the International Union Against Cancer tumour node metastasis (TNM) classification5. Information on TNM stage was not available for the English data, as stage was not recorded routinely by the English registries.
The hospital (in England these were described by the registry as trusts that can be responsible for several individual hospitals) where the operation was performed was available in all data sets. Annual hospital volume was defined separately for oesophagectomy and gastrectomy as the number of resections per hospital in each calendar year. Volume categories were defined according to the distribution of number of resections among hospitals (Fig. S1, supporting information).
Data regarding oesophagectomies and gastrectomies were analysed separately. Differences in patient characteristics, resection rates and annual hospital volumes between countries were analysed with the χ2 test.
Postoperative mortality was defined as death from any cause within 30 days after surgery. Differences in 30-day mortality between countries were analysed by means of generalized estimating equations, adjusting for available case-mix factors (sex, age, morphology) and clustering of patients within hospitals using a random hospital effect model6. Two-year overall survival after surgery was chosen as the long-term outcome because of the relatively short follow-up period owing to the recent nature of the data, and calculated from the day of surgery until death from any cause (event) or alive at last follow-up (censored). Details of the cause of death were not available. Unadjusted 2-year overall survival rates for each country were calculated by Kaplan–Meier analysis. Adjusted differences in 2-year overall survival between countries were analysed by Cox regression, adjusting for case-mix factors as categorical co-variables (sex, age, morphology, stage) and clustering of patients within hospitals. English patients were excluded from the adjusted 2-year survival analyses as stage data were not available.
Differences in outcomes between hospital volume categories were evaluated in the same way as differences in outcomes between countries, including the adjustment for clustering of patients within hospitals. An interaction analysis was performed between country and annual hospital volume. Annual hospital volume was analysed both as a categorical and as a linear variable. Statistical analyses were performed with SPSS® version 17.0.2 (IBM, Armonk, New York, USA) and R version 2.12.2 (http://www.r-project.org).
The Swedish registries with more than 90 per cent case ascertainment were in Uppsala–Örebro (2006–2009), Norra (2006–2009), Sydöstra (2007–2009) and Stockholm–Gotland (2008–2009). Not all countries had complete data for each year (Fig.1). Between January 2004 and December 2009, 84 630 patients with a diagnosis of oesophageal or gastric cancer were registered in the Netherlands, Denmark or England. Resection rates were similar in the Netherlands and Denmark: 28·5–29·9 per cent for oesophageal cancer and 41·4–41·9 per cent for gastric cancer. Resection rates in England were significantly lower: 18·2 per cent for oesophageal cancer and 21·6 per cent for gastric cancer (both P < 0·001).
Characteristics of patients who underwent resection
Between 2004 and 2009, 19 864 patients underwent oesophagectomy or gastrectomy for cancer (Table2). Median age was 64 years for all patients who underwent oesophagectomy and 71 years for those who underwent gastrectomy. The percentage of patients aged over 75 years undergoing resection was lowest in Denmark, 7·1 per cent for oesophagectomy and 22·7 per cent for gastrectomy, compared with 9·9–10·8 per cent for oesophagectomy and 32·4–38·4 per cent for gastrectomy in the other countries. The highest proportion of patients with stage I tumours (oesophagectomy 15·8 per cent, gastrectomy 34·2 per cent) and the highest proportion of stage IV disease (oesophagectomy 12·0 per cent, gastrectomy 17·1 per cent) were recorded in the Netherlands.
Table 2. Characteristics of 10 854 patients who underwent oesophagectomy and 9010 who underwent gastrectomy for cancer
Median follow-up for all patients was 37 months. Exact in-hospital mortality data were not available from all four data sources. In all countries, the postoperative 30-day mortality rate was lower after oesophagectomy (4·6 per cent) than after gastrectomy (6·7 per cent), but variation between countries was considerable. The adjusted 30-day mortality rate after oesophagectomy was lowest in Sweden (1·9 per cent) and highest in England (5·8 per cent) (P = 0·028) (Fig.2a, Table3). Differences between other countries were not significant. After gastrectomy, the adjusted 30-day mortality rate in the Netherlands (6·9 per cent) was significantly higher than in Sweden (3·5 per cent; P = 0·017) and Denmark (4·3 per cent; P = 0·029) (Fig.2b).
Table 3. Differences in postoperative 30-day mortality and 2-year survival between countries
Unadjusted 2-year overall survival estimates were not significantly different between countries, except for 2-year survival after gastrectomy between the Netherlands and England (51·9 versus 56·3 per cent; P < 0·001) (Fig. S2, supporting information). Adjusted 2-year survival rates were not significantly different between the Netherlands, Sweden and Denmark, in either resection group (Table3; Fig. S3, supporting information)
Annual hospital volumes for oesophagectomy were higher than for gastrectomy (Fig. S1, supporting information). The variation between countries is shown in Fig.3. In Denmark, 65·6 per cent of oesophagectomies were performed in hospitals with an annual volume above 30 procedures per year, whereas a similar proportion (63·6 per cent) was performed in Sweden in hospitals with an annual volume of fewer than 11 per year. In Denmark, 58·9 per cent of all gastrectomies for cancer were performed in hospitals with an annual volume above 20 per year, whereas in the Netherlands and Sweden 75·2 and 76·1 per cent of gastric resections respectively were performed in hospitals with an annual volume of less than 11 per year. In England, 68·9 per cent of gastrectomies were performed in hospitals with an annual volume of less than 21 per year.
Increasing hospital volume was associated with significantly lower postoperative mortality rates, after both oesophagectomy and gastrectomy (Fig.4, Table 4). The adjusted 30-day mortality rate after oesophagectomy in hospitals with an annual volume of at least 41 per year was lower than in hospitals with an annual volume of less than 11 per year (4·3 versus 7·2 per cent; P < 0·001). The adjusted 30-day mortality rate after gastrectomy in hospitals with an annual volume of at least 21 per year was also lower than in hospitals with an annual volume of less than 11 per year (4·4 versus 6·7 per cent; P = 0·047). Testing for interaction between country and hospital volume category revealed a significant interaction regarding postoperative 30-day mortality after oesophagectomy, which was the result of a stronger volume–outcome relation in Denmark than in the other countries (data not shown). No such interaction was found for gastrectomy.
Table 4. Multivariable analysis of effect of annual hospital volume on 30-day mortality and 2-year survival
High hospital volume was also significantly associated with better 2-year survival after oesophagectomy, with a hazard ratio of 0·79 (95 per cent confidence interval 0·66 to 0·96) for the highest-volume group (at least 41 per year) compared with the lowest-volume group (1–10 per year). Following gastrectomy, there was no significant association between hospital volume and 2-year survival (Table4; Fig. S4, supporting information) and no interaction between country and hospital volume category regarding 2-year survival.
This study has shown variations in annual hospital volumes for oesophagectomy and gastrectomy across four European countries. The hospital volumes were highest in Denmark. Resection rates were similar in the Netherlands and Denmark, but considerably lower in England. The postoperative 30-day mortality rate was lowest in Sweden, after both oesophagectomy and gastrectomy, and the 30-day mortality rate after gastrectomy was significantly higher in the Netherlands than in Sweden and Denmark. Larger numbers of stage I and stage IV oesophageal and gastric cancers were resected in the Netherlands than in the other countries. Increasing hospital volume was associated with lower postoperative mortality after both oesophagectomy and gastrectomy. Two-year adjusted survival after surgery was similar in each country, with longer overall survival after oesophagectomy compared with gastrectomy.
Studies on outcomes after cancer surgery are commonly based on data from clinical trials or patient cohorts from specialized surgical centres. Owing to selection, these series may not reflect practice in general and cannot be used to compare outcomes between countries. Population-based studies, as performed by EUROCARE, provide insight into the differences in mortality and survival patterns between countries1. In the EUROCARE framework, however, registry data may be incomplete for some countries and recent information is not available. The methodology was intended for incidence and survival trend analyses, not for monitoring clinical practice or providing feedback to individual healthcare providers. Nationwide clinical audits, as currently performed in the UK, Sweden, Denmark and the Netherlands, provide detailed information on patient, tumour, treatment and hospital characteristics, and data are quickly available for comparative analyses. A disadvantage of clinical audits is that data are reported by the healthcare provider and are therefore not always complete. In contrast, cancer registries mostly include all available patients, but the information captured is less detailed. In the present study, information on patient co-morbidities was missing from the Dutch and English data set, and tumour stage from the English data set. This lack of this information may have biased outcome and partly explain some of the differences.
In the present study, resection rates for both oesophageal and gastric cancer were lower in England than in the Netherlands and Denmark (and not available in Sweden). The UK NOGCA has confirmed a steady reduction in resection rates over the past decade, describing rates of curative resection for oesophageal junctional and gastric cancer of 33 and 31 per cent respectively in 1998, decreasing to 24 and 23 per cent in 20057. This has been attributed to improved preoperative staging and multidisciplinary management, thereby better selecting patients for surgery8. Comparison of resection rates is also confounded by differences in clinical practice, but with the present data sets no conclusions can be drawn on which country has the optimal resection rate. This should be addressed in future studies if adequate information on preoperative staging is included.
A Dutch study published in 2001 showed lower postoperative mortality rates after oesophagectomies in high-volume hospitals, and as of 2006 oesophagectomy in the Netherlands was centralized with a minimum annual volume of ten per year9. As of 2011, this was increased to 20 per year. Over the study period, there was no minimum volume standard for gastrectomy in the Netherlands, but gastrectomies will be centralized from 2012. In addition, a national oesophagogastric cancer audit was started in 201110. This may answer why the resection rate in stage IV disease was higher than elsewhere, perhaps reflecting practice in smaller hospitals where preoperative assessment may be less robust.
In Sweden, a national oesophagogastric cancer audit was initiated in 2006. Both oesophagectomies and gastrectomies were performed in low volumes, but recently Sweden has also started to centralize upper gastrointestinal surgery. A nationwide oesophagogastric cancer registry has been initiated in Denmark. Upper gastrointestinal surgery was restricted to five centres in 2003, reducing to four centres in 200811. This was accompanied by reduced postoperative mortality after gastrectomy and an increase in the number of evaluated lymph nodes, often used as a quality indicator in gastric cancer surgery12. In the present study, hospital volumes in Denmark were higher than in any other country, with the majority of oesophagectomies being performed in hospitals with a volume of over 40 per year. In England, Wales and Northern Ireland, a National Health Services Cancer Plan became effective in 200113. In this plan, recommendations were made to centralize oesophagogastric cancer surgery to centres with a population base of between one and two million, establish specialist treatment teams, and audit all steps in oesophagogastric cancer care14. By 2008 and 2009, 82 per cent of oesophageal and gastric cancer resections were done in 41 designated centres, with 63 per cent of oesophagectomies and 65 per cent of gastrectomies being performed in high-volume centres (at least 50 resections per year)15. Centralization of surgery is not unique to Europe. A recent US study described centralization of several surgical procedures, including oesophagectomy for cancer, that resulted in a decrease in postoperative mortality16.
Owing to its population-based nature, the present study provides an accurate comparison of postoperative mortality and long-term survival after oesophagectomy and gastrectomy between several countries in Europe. However, the variability in the recorded data and missing information on patient co-morbidities, multimodality therapy and cause-specific survival makes it impossible to explain properly the differences between countries simply in terms of annual hospital volumes. Sweden had lower postoperative mortality rates than the other countries, even after adjustment for case mix, without performing surgery in high-volume institutions. High-quality healthcare with nationwide quality assurance programmes might have contributed to the these results17. Differences in selecting patients for surgery between Sweden and the other countries could be a factor and the inclusion only of regions in Sweden with high case ascertainment may also have biased the findings. On the contrary, the postoperative mortality rate after gastrectomy in the Netherlands was high. This might be explained by the absence of a quality assurance programme during the studied period for gastric cancer surgery in the Netherlands. Differences in unadjusted 2-year survival rates between countries should be interpreted with care, as tumour stage distributions in the group of patients who underwent surgical resection might have differed between countries.
The relationship between annual hospital volume and postoperative mortality after oesophagectomy and gastrectomy has been investigated extensively16, 18. For oesophagectomy, most studies have found a benefit for high-volume surgery19. Results regarding hospital volumes for gastrectomies are less uniform, some finding no effect on postoperative mortality20–23. Patient numbers in these studies, however, were relatively small (below 5000) compared with those in which a benefit for gastrectomies in high-volume centres was found (up to 56 000)24–27.
The evidence on hospital volume in relation to long-term survival is limited. Among four studies of oesophagectomy, two were positive28–31, and five of seven gastrectomy studies were positive27, 32–37. In the present study, a significant relationship between annual hospital volume and postoperative mortality was found for both oesophagectomy and gastrectomy. Furthermore, increasing hospital volume for oesophagectomy was associated with improved long-term survival. No such relationship was found for gastrectomy; this might be explained by the low threshold of what was considered ‘high-volume surgery’ (21or more procedures per year).
It could be argued that in the present study individual surgeon volumes should have been analysed as well as hospital volume. Quality of care and outcomes, however, are the result of collaboration between different professionals, including surgeons, anaesthetists, intensive care unit staff and nursing staff. All these disciplines contribute to outcomes38. The role of the individual surgeon is important, but attribution of results solely to the surgeon is open to misinterpretation. Using hospital volume as the only basis for determining outcome quality has also been criticized24. There can be low-volume hospitals with excellent outcomes and vice versa. Outcome-based referral avoids this problem, by selecting centres of excellence based on case mix-adjusted outcomes. It has been used to centralize oesophagectomy in one part of the Netherlands, which led to a reduction in the postoperative mortality rate from 12 to 3 per cent over a 10-year period39.
There were considerable differences between the four European countries involved in the present study regarding resection rates, postoperative 30-day mortality rates and annual hospital volumes in oesophagogastric cancer surgery. Increasing hospital volume was associated with better outcomes, but differences in outcomes between countries could not be explained by these differences in annual hospital volumes. Nationwide clinical audits aim to identify centres of excellence based on case mix-adjusted outcomes. On an international level, these audits can be used to understand differences in outcomes between countries, but require uniform definitions and registration of data. The present study highlights the need to collect standard clinical data in each country to facilitate international comparisons, analogous to the EURECCA initiative for colorectal cancer40. A European oesophageal and gastric cancer audit could provide further insight into differences between countries, leading to better quality of care for patients with oesophageal and gastric cancer.
L. G. M. van der Geest (Comprehensive Cancer Centre The Netherlands, Utrecht, The Netherlands), H. J. Larsson (Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark), A. Cats (Department of Gastroenterology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands) and M. Verheij (Department of Radiotherapy, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands).
This study was funded by the Signalling Committee on Cancer of the Dutch Cancer Society (KWF Kankerbestrijding). The study sponsor had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Disclosure: The authors declare no conflict of interest.
Additional supporting information may be found in the online version of this article:
Appendix A. Distribution of annual hospital volumes. (a) Oesophagectomy (N=10854); (b) Gastrectomy (N=9010)
Appendix B. Two-year survival, adjusted for sex, age, histology, and stage group, in the Netherlands, Sweden, and Denmark. Survival estimates and 95% confidence intervals are provided in Table 3. (a) Oesophagectomy; (b) Gastrectomy
Appendix C. Unadjusted two-year survival separately analyzed per country, Kaplan Meier analysis. Survival estimates and 95% confidence intervals are provided in Table 3. (a) Oesophagectomy; (b) Gastrectomy
Appendix D. Two-year survival, adjusted for sex, age, histology, and stage group, by annual hospital volume category. (a) Oesophagectomy; (b) Gastrectomy