The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis.

PURPOSE: To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics. PATIENTS AND METHODS: We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY. CONCLUSION: The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.

Chemoprevention of colorectal cancer: systematic review and economic evaluation.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the UK: incidence increases with age, median age at diagnosis being over 70 years. Approximately 25% of cases occur in individuals with a family history of CRC, including 5% caused by familial adenomatous polyposis (FAP) or hereditary non-polyposis CRC (HNPCC). Most develop from adenomatous polyps arising from the intestine lining. Individuals with these polyps undergo polypectomy and are invited for endoscopic surveillance. Screening via faecal occult blood testing has been rolled out across the UK. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of drug and micronutrient interventions for the prevention of CRC and/or adenomatous polyps. Interventions considered include: non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclo-oxygenase-2 (COX-2) inhibitors; folic acid; calcium; vitamin D and antioxidants (including vitamin A, vitamin C, vitamin E, selenium and beta-carotene). Chemoprevention was assessed in the general population, in individuals at increased risk of CRC, and in individuals with FAP or HNPCC. DATA SOURCES: A systematic review identified randomised controlled trials (RCTs) assessing drug and nutritional agents for the prevention of CRC or adenomatous polyps. A separate search identified qualitative studies relating to individuals' views, attitudes and beliefs about chemoprevention. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL Register of Controlled Trials, DARE, NHS-EED (NHS Economic Evaluation Database), HTA database, Science Citation Index, BIOSIS previews and the Current Controlled Trials research register were searched in June 2008. Data were extracted by one reviewer and checked by a second. REVIEW METHODS: The synthesis methods used were systematic review and meta-analysis for RCTs and qualitative framework synthesis for qualitative studies. A health economic model was developed to assess the cost-effectiveness of chemoprevention for two populations with different levels of risk of developing CRC: the general population and an intermediate-risk population. RESULTS: The search identified 44 relevant RCTs and six ongoing studies. A small study of aspirin in FAP patients produced no statistically significant reduction in polyp number but a possible reduction in polyp size. There was a statistically significant 21% reduction in risk of adenoma recurrence [relative risk (RR) 0.79, 95% confidence interval (CI) 0.68 to 0.92] in an analysis of aspirin versus no aspirin in individuals with a history of adenomas or CRC. In the general population, a significant 26% reduction in CRC incidence was demonstrated in studies with a 23-year follow-up (RR 0.74, 95% CI 0.57 to 0.97). Non-aspirin NSAID use in FAP individuals produced a non-statistically significant reduction in adenoma incidence after 4 years of treatment and follow-up and reductions in polyp number and size. In individuals with a history of adenomas there was a statistically significant 34% reduction in adenoma recurrence risk (RR 0.66, 95% CI 0.60 to 0.72) and a statistically significant 55% reduction in advanced adenoma incidence (RR 0.45, 95% CI 0.35 to 0.58). No studies assessed the effect of non-aspirin NSAIDs in the general population. There were no studies of folic acid in individuals with FAP or HNPCC. There was no significant effect of folic acid versus placebo on adenoma recurrence (RR 1.16, 95% CI 0.97 to 1.39) or advanced adenoma incidence in individuals with a history of adenomas. In the general population there was no significant effect of folic acid on risk of CRC (RR 1.13, 95% CI 0.77 to 1.64), although studies were of relatively short duration. Calcium use by FAP patients produced no significant reduction in polyp number or disease progression. In individuals with a history of adenomas there was a statistically significant 18% reduction in risk of adenoma recurrence (RR 0.82, 95% CI 0.69 to 0.98) and a non-significant reduction in risk of advanced adenomas (RR 0.77, 95% CI 0.50 to 1.17). In the general population there was no significant effect of calcium on risk of CRC (RR 1.08, 95% CI 0.87 to 1.34), although studies were of relatively short duration. There were no studies of antioxidant use in individuals with FAP or HNPCC, and in individuals with a history of adenomas no statistically significant differences in relative risk of adenoma recurrence were found. In the general population there was no difference in incidence of CRC (RR 1.00, 95% CI 0.88 to 1.13) with antioxidant use compared with no antioxidant use. Twenty studies reported qualitative findings concerning chemoprevention. People are more likely to use NSAIDs if there is a strong perceived need. Perceptions of risk and benefit also influence decision-making and use. People have fewer concerns about using antioxidants or other supplements, but their perception of the benefits of these agents is less well-defined. The model analysis suggested that the most cost-effective age-range policy in the general population would be to provide chemoprevention to all individuals within the general population from age 50 to 60 years. The use of aspirin in addition to screening within the general population is likely to result in a discounted cost per life-year gained of around 10,000 pounds and a discounted cost per quality-adjusted life-year (QALY) gained of around 23,000 pounds compared with screening alone. In the intermediate-risk group the most economically viable age-range policy would be to provide chemoprevention to individuals following polypectomy aged 61 to 70 years. Calcium is likely to have a discounted cost per QALY gained of around 8000 pounds compared with screening alone. Although aspirin in addition to screening should be more effective and less costly than screening alone, under the current assumptions of benefits to harms of aspirin and calcium, aspirin is expected to be extendedly dominated by calcium. LIMITATIONS: Whilst a number of studies were included in the review, the duration of follow-up was generally insufficient to detect an effect on cancer incidence. Given the uncertainties and ambiguities in the evidence base, the results of the health economic analysis should be interpreted with caution. CONCLUSIONS: Aspirin and celecoxib may reduce recurrence of adenomas and incidence of advanced adenomas in individuals with an increased risk of CRC and calcium may reduce recurrence of adenomas in this group. COX-2 inhibitors may decrease polyp number in patients with FAP. There is some evidence for aspirin reducing the incidence of CRC in the general population. Both aspirin and NSAIDs are associated with adverse effects so it will be important to consider the risk-benefit ratio before recommending these agents for chemoprevention. The economic analysis suggests that chemoprevention has the potential to represent a cost-effective intervention, particularly when targeted at intermediate-risk populations following polypectomy.

Cost-effectiveness of prophylactic surgery for duodenal cancer in familial adenomatous polyposis.

BACKGROUND: Duodenal cancer is the leading cause of cancer death in familial adenomatous polyposis after colorectal cancer. The lifetime risk for developing duodenal cancer is 4% to 10%. Current treatment guidelines recommend endoscopic surveillance with a prophylactic pancreaticoduodenectomy in advanced duodenal polyposis, defined using the Spigelman staging system. Because no clinical trials have assessed this recommendation, a modeling approach was used to evaluate the cost-effectiveness of various treatment strategies. METHODS: A Markov model was constructed to estimate the life expectancy and cost of three different strategies: pancreaticoduodenectomy at Spigelman stage III, pancreaticoduodenectomy at Spigelman stage IV, and pancreaticoduodenectomy at cancer diagnosis. A cohort of 30-year-old familial adenomatous polyposis patients with total colectomies was simulated until age 80. The analysis was from a societal perspective. Extensive sensitivity analysis was performed to assess the impact of model uncertainty on results. RESULTS: At all stages of polyposis and all ages <80 years, prophylactic surgery at Spigelman stage IV resulted in the greatest life expectancy. Surgery at stage IV was more effective and more expensive than surgery at cancer diagnosis, with an incremental cost of $3,200 per quality-adjusted life year gained. Surgery at stage III was not a viable option. The results were robust to wide variation in model parameters but were sensitive to the post-pancreaticoduodenectomy quality of life score. CONCLUSIONS: Prophylactic pancreaticoduodenectomy at stage IV duodenal polyposis in familial adenomatous polyposis is a cost-effective approach that results in greater life expectancy than surgery at either stage III or cancer diagnosis.

[An economic assessment of genetic testing for familial adenomatous polyposis]. / Evaluación económica de la prueba genética de la poliposis adenomatosa familiar.

OBJECTIVE: To analyze the cost-effectiveness of genetic testing for first-degree relatives of patients with colon cancer to identify mutations in the APC gene (Adenomatous Polyposis Coli). METHODOLOGY: Analyses were performed from the perspective of the health system. We used a Markov model. We compared genetic testing for the APC gene, the cause of familial adenomatous polyposis (FAP), which results in colon cancer, versus no genetic testing for said gene. The effectiveness measure used was quality-adjusted life-years (QALYs), and costs were measured in euros for 2005. The costs of interventions were extracted from the costs of health services provided by centers under the Andalusian Public Health System, and other parameters were obtained from the literature. RESULTS: The performance of genetic testing is the dominant strategy when compared to the absence of genetic testing given the latter option has an incremental cost of 7,676.34 euros and is less effective. A sensitivity analysis found that genetic testing remains the dominant strategy for a plausible range of costs of the test itself, and for the probability of developing adenocarcinoma. CONCLUSIONS: Our analysis showed that in this patient group genetic testing to detect APC gene mutations is on average less costly and improves QALYs versus no testing.

Cost-utility analysis of genetic screening in families of patients with germline MUTYH mutations.

BACKGROUND: MUTYH associated polyposis (MAP) is an autosomal recessive inherited disorder. Carriers of bi-allelic MUTYH germline mutations have a risk of approximately 60% to develop colorectal carcinoma (CRC). In the general population about 1.5% is a heterozygous MUTYH mutation carrier. Children of MAP patients have an increased risk of inheriting two MUTYH mutations compared to the general population, implicating an increased risk for developing CRC. METHODS: Using data from the literature and Dutch MAP patients (n = 40), we constructed a Markov model to perform a societal cost-utility analysis of genetic screening in MAP families. Genetic screening was done by testing the spouse first and, in case of a heterozygous spouse, also testing of the children. RESULTS: The cost of genetic screening of families of MAP patients, when compared to no genetic screening, was estimated at 25,000 euros per quality-adjusted life year (QALY). The presence of Fecal Occult Blood testing (FOBT) population screening only slightly increased this cost-utility ratio to 25,500 euros per QALY. For a MUTYH heterozygote index-patient, the ratio was 51,500 euros per QALY. The results of our analysis were sensitive to several of the parameters in the model, including the cost assumed for molecular genetic testing. CONCLUSION: The costs per QALY of genetic screening in families of MAP patients are acceptable according to international standards. Therefore, genetic testing of spouses and/or children should be discussed with and offered to counselees.

Implementation of a clinical pathway decreases length of stay and hospital charges for patients undergoing total colectomy and ileal pouch/anal anastomosis.

BACKGROUND: Clinical pathways are increasingly being used by hospitals to improve efficiency in the care of certain patient populations; however, little prospective data are available to support their use. This study examined whether using a clinical pathway for patients undergoing ileal pouch/anal anastomosis, a complex procedure in which we had extensive practical experience, affected hospital charges or length of stay (LOS). METHODS: A clinical pathway was developed to serve patients undergoing elective total colectomy and ileal pouch/anal anastomosis. All operations were performed by two attending physicians (J.E.F., M.S.N.). Before implementation, 10 pilot patients were prospectively monitored to ensure that hospital charges were accurately generated. In addition, charge audits were performed by an outside agency to verify the accuracy of the hospital bills. The pathway was then implemented, and 14 patients were prospectively analyzed. RESULTS: In all patients the principal diagnosis was ulcerative colitis, with the exception of three patients with familial polyposis. Mean external audit charges were within 2% of the hospital bills; therefore the hospital bills were used in all calculations. The mean LOS decreased from 10.3 days to 7.5 days (p = 0.046) for patients on the pathway versus pilot patients. Mean hospital charges also decreased significantly, from $21,650 to $17,958 per patient (p = 0.005). CONCLUSIONS: Implementation of a clinical pathway, even for an operation in which the surgeon has much experience, is an effective method for reducing LOS and charges for patients. This is likely the result of interdisciplinary cooperation, elimination of unnecessary interventions, and streamlined involvement of ancillary services. These results support the development of clinical pathways for procedures that involve routine preoperative and postoperative care. In addition, the benefits of clinical pathways should increase proportionally with increasing case volume for a particular procedure.

[Effectiveness and costs of screening colonoscopy]. / Nutzen und Kosten der Screeningkoloskopie.

Screening colonoscopy is always indicated when rectosigmoidoscopy reveals an adenoma, since this lesion roughly doubles the patient's risk of contracting colonic cancer. Follow-up should be performed at intervals of about three years after endoscopic removal of all colorectal polyps. Repeated screening examinations are recommended for the following genetic diseases that carry an increased risk of colorectal carcinoma: familial adenomatous polyposis (FAP) and its genetic variant, hereditary non-polyposis colorectal cancer syndrome (HNPCC) and hamartomatous polyposis syndromes (e.g. Peutz-Jeghers). Also in the case of familial "sporadic" carcinoma of the colon, regular screening colonoscopies for first degree relatives are recommended. Although the use of regular screening colonoscopies in patients with a long history of extensive ulcerative colitis is controversial, the recent results support such examinations. While the benefit of screening colonoscopy or sigmoidoscopy of the general population from the age of 50 onward must be affirmed, it should be weighed against the costs involved in such an undertaking. At the present time, the American Cancer Society recommends that from the age of 50 onward, the annual fecal test for occult blood should be supplemented by sigmoidoscopy performed every three to five years.