Epidemiology and background
Pseudomyxoma peritonei (PMP) refers to a progressive disease process within theperitoneum, thought to originate in the appendix and characterised by the production ofcopious amounts of mucinous fluid resulting in a 'jelly belly'. If untreated thecondition is fatal. Uncertainty persists as to the specific definition, pathology, siteof origin and prognosis of PMP. It is a rare condition, with approximately 50 new casesin England and Wales each year, affecting men and women equally with increased incidencewith age. Patients' median survival is approximately 6 years, with 50-70% surviving for5 years and 10-32% for 10 years. Patients most commonly present with acute appendicitisor increasing abdominal girth. Although there are several treatment options, mostpatients will undergo either standard treatment of debulking surgery or radical surgeryand concomitant perioperative intraperitoneal chemotherapy (IPEC) (Sugarbakerprocedure).
Objectives
This systematic review examines the clinical and cost-effectiveness of the Sugarbakerprocedure for treating PMP and the costs of the procedure in the UK.
Methods
This report was based on a systematic literature review and modelling of costs.
Data sources
The main electronic databases were searched, with English language limits, for theperiods up to September 2002. Bibliographies of related papers were assessed forrelevant studies and experts contacted for advice and peer review, and to identifyadditional published and unpublished references.
Study selection
Studies were included if they fulfilled the following criteria, which were applied byone reviewer and checked by a second reviewer, with any disagreements resolvedthrough discussion.
Intervention: (1) traditional surgery debulking resection of all gross disease,(2) cytoreductive surgery combined with chemotherapy or cytoreductive surgerycombined with heated adjuvant IPEC (Sugarbaker procedure).
Participants: people diagnosed as having PMP characterised by histologicallybenign tumours with indolent course originating in the appendix.
Outcomes: survival, recurrence or quality of life as primary outcomes andcomplications as secondary outcome with a minimum of 2 years' follow-up.
Design: the highest level of evidence available, which was case series.Economic evaluations were included in the review if they included a comparator(or placebo) and both the costs and consequences (outcomes) or if they werecosting studies.
Data extraction
Data extraction and quality assessment were undertaken by one reviewer and checked bya second reviewer, with any disagreements resolved through discussion. The quality ofcase series was assessed using criteria recommended by the NHS Centre for Reviews andDissemination (University of York). The quality of economic studies was assessed fortheir internal validity using a standard checklist, and external validity using aseries of relevant questions.
Study synthesis
The clinical effectiveness of the Sugarbaker procedure for PMP was synthesisedthrough a narrative review with full tabulation of results of all included studies.The economic modelling used a Monte-Carlo simulation model, populated UK price data,to estimate likely UK costs.
Results
Number and quality of studies, and direction of evidence
Five retrospective case-series reports assessing the Sugarbaker procedure met theinclusion criteria for the review. No studies comparing the Sugarbaker procedure withstandard treatment, or observational studies of standard treatment were included.When judged using standard criteria for assessing methodological quality, the studieswere found to be of poor quality. Patients with different histopathology may havebeen included in the studies. Details of cytoreductive surgery and chemotherapydiffered between studies and not all patients within a series received the sametreatment.
Summary of benefits
There appears to be some benefit for people with PMP who undergo treatment with theSugarbaker procedure. People with PMP have an estimated 5-year and 10-year survivalof approximately 50% and 18%, respectively. In contrast, the survival rate ofpatients following the Sugarbaker procedure is about 90% at 2 years, 60% to about 90%at 3 years, depending on details of IPEC, and 60% to about 68% at 10 years. Thepercentage of patients with no evidence of disease at the end of follow-up after theSugarbaker procedure ranged from 41 to 82%. Similarly, the percentage of patientsalive with disease at the end of follow-up ranged from 9 to 35%. Mortality due todisease ranged from 2 to 31% in the included studies of the Sugarbaker procedure.Commonly reported complications of the Sugarbaker procedure were anastomotic leaks,fistula formation, wound infection, small bowel perforations/obstructions andpancreatitis.
Costs
No cost-effectiveness or high-quality cost evidence was included in the systematicreview. One study of poor methodological quality and set in the USA was found. Thisstudy, together with UK unit price data and expert advice, was used to populate aMonte-Carlo simulation model to estimate the marginal cost of operating a service toprovide treatment for PMP using the Sugarbaker technique rather than standardtreatment. The Monte-Carlo simulation model did not include the costs incurred insetting up the specific service or training the staff. The results of the Monte-Carlosimulation model showed that the cost for one patient over a maximum of 5 years wouldbe about £9700, with a standard deviation of about £1300. The US study showed aten-fold higher cost. However, the two studies may not be entirely comparable owingto differences in the provision of the specific service and the organisation of thehealth service.
Cost-utility
No relevant data were available.
Sensitivity analyses
The Monte-Carlo analysis showed that the variation around the mean was not very high.The most likely factor influencing the variation of the costs was the length ofprocedure. No sensitivity analysis could be done of the alternative treatment.
Conclusions
Limitations of the calculations
The economic results should be seen as merely an example of the likely marginal costsof the Sugarbaker procedure. No policy decision can be made from cost statementswithout more information about the current alternative. Other questions concerningthe capacity and finances of the chosen method have to be left to others.
Implications of Sugarbaker for PMP
If the National Specialist Commissioning Advisory Group were to support thedevelopment of additional specialist centres within the NHS, there may be severalbarriers to implementation. The Sugarbaker procedure requires trained and experiencedstaff and inevitably there will be the need for a period of training and time costsinvolved in developing the appropriate teams. Although the procedure requires somespecialist equipment and maintenance, such as smoke evacuators, these should havelimited effect on setting up the service. PMP is a relatively rare condition withapproximately 50 new cases per year in the UK and the impact of an increase in thedemand for services should be limited.
Recommendations for research
Evidence is needed for the effectiveness of maximal cytoreductive surgery compared withsurgical debulking, using different intraoperative IPEC strategies, and for theeffectiveness of treatments in patients who have residual disease following maximalefforts at cytoreduction. Research should take the form of high-quality prospectivecohort studies with economic evaluations. Studies should be in histologicallyhom*ogeneous groups and follow-up should be long enough to assess outcomes such asmortality, survival, recurrence, morbidity, complications and quality of life.
Publication
Bryant J, Clegg AJ, Sidhu MK, Brodin H, Royle P, Davidson P. Clinical effectiveness andcosts of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.Health Technol Assess 2004;8(7). [PubMed: 14960255]
NHS R&D HTA Programme
The NHS R&D Health Technology Assessment (HTA) Programme was set up in 1993 toensure that high-quality research information on the costs, effectiveness and broaderimpact of health technologies is produced in the most efficient way for those who use,manage and provide care in the NHS.
The research reported in this monograph was commissioned by the HTA Programme on behalfof the National Specialist Commissioning Advisory Group to inform policy development.The Technology Assessment Report brings together evidence on key aspects of the use ofthe technology concerned.
The research reported in this monograph was funded as project number 02/14/01.
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