Comparison Between Universal Immunohistochemistry for Mismatch Repair Proteins Versus Revised Bethesda Guidelines in the Detection of Patients With Lynch Syndrome

Pérez–Carbonell, Lucía; Guarinós, Carla; Soler, María Rodríguez; Sánchez–Fortún, Cristina; Sempere-Robles, Laura; Ruíz-Ponte, Clara; Castillejo, Adela; Brea, Alejandro; Carracedo, Angel; Barberá, Víctor Manuel; Rojas, Estefanía; Bujanda, Luís; Clofent, Joan; Andreu, Montserrat; Llor, Xavier; Castells, Antoni; Soto, José Luís; Jover, Rodrigo

doi:10.1016/s0016-5085(11)60394-6

Cited by 4 publications

(10 citation statements)

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“…34,[59][60][61][62][63][64][65][66][67][68][69][70][71][72] All studies were published between 2000 and 2012 and summary details of each study can be found in Tables 31 and 32.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

“…70,72 Most studies were not specific about the 'current practice' in their respective countries, but their strategies were generally compared against a no testing strategy, implying that there was no standard 'current practice' in each of the countries or that no testing for LS was the 'current practice'. Relevant to our assessment, one of the European studies was based in the UK, 60 but this was 9 years old at the time of writing and was not consistent with our input population; Pigatto and colleagues 60 investigated families referred for genetic testing, rather than newly diagnosed CRC patients aged < 50 years, who were the focus of our investigation.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

“…As well as having different study populations, the different studies also assessed different tests, which included the following subsets: clinical criteria/FH, 34,[59][60][61]63,64,67,68,70 prediction models, 66 tumour testing 65,34,[59][60][61][62][63][64][66][67][68][69][70][71][72] and genetic testing. 65,34,[59][60][61][62][63][64][66][67][68][69][70][71][72] Genetic testing was split into gene sequencing for probands and targeted genetic testing for relatives.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

“…65,34,[59][60][61][62][63][64][66][67][68][69][70][71][72] Genetic testing was split into gene sequencing for probands and targeted genetic testing for relatives. Not all genetic testing was conducted on all four known LS genes, primarily because MSH6 and PMS2 are more recent discoveries.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

“…With regards to the study design, nine papers 34,[60][61][62][63][64]66,68,70 included primary research (prospective or clinical) and 12 34,[59][60][61][62][63][65][66][67]69,71,72 included some form of decision modelling, usually using a decision tree approach. Six papers 34,[60][61][62][63]66 used a combination, using the study to inform the decision tree results.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

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A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome

Snowsill

Huxley

Hoyle

et al. 2014

Health Technology Assessment

106

234

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BackgroundLynch syndrome (LS) is an inherited autosomal dominant disorder characterised by an increased risk of colorectal cancer (CRC) and other cancers, and caused by mutations in the deoxyribonucleic acid (DNA) mismatch repair genes.ObjectiveTo evaluate the accuracy and cost-effectiveness of strategies to identify LS in newly diagnosed early-onset CRC patients (aged < 50 years). Cascade testing of relatives is employed in all strategies for individuals in whom LS is identified.Data sources and methodsSystematic reviews were conducted of the test accuracy of microsatellite instability (MSI) testing or immunohistochemistry (IHC) in individuals with CRC at risk of LS, and of economic evidence relating to diagnostic strategies for LS. Reviews were carried out in April 2012 (test accuracy); and in February 2012, repeated in February 2013 (economic evaluations). Databases searched included MEDLINE (1946 to April week 3, 2012), EMBASE (1980 to week 17, 2012) and Web of Science (inception to 30 April 2012), and risk of bias for test accuracy was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) quality appraisal tool. A de novo economic model of diagnostic strategies for LS was developed.ResultsInconsistencies in study designs precluded pooling of diagnostic test accuracy results from a previous systematic review and nine subsequent primary studies. These were of mixed quality, with significant methodological concerns identified for most. IHC and MSI can both play a part in diagnosing LS but neither is gold standard. No UK studies evaluated the cost-effectiveness of diagnosing and managing LS, although studies from other countries generally found some strategies to be cost-effective compared with no testing.The de novo model demonstrated that all strategies were cost-effective compared with no testing at a threshold of £20,000 per quality-adjusted life-year (QALY), with the most cost-effective strategy utilising MSI andBRAFtesting [incremental cost-effectiveness ratio (ICER) = £5491 per QALY]. The maximum health benefit to the population of interest would be obtained using universal germline testing, but this would not be a cost-effective use of NHS resources compared with the next best strategy. When the age limit was raised from 50 to 60 and 70 years, the ICERs compared with no testing increased but remained below £20,000 per QALY (except for universal germline testing with an age limit of 70 years). The total net health benefit increased with the age limit as more individuals with LS were identified. Uncertainty was evaluated through univariate sensitivity analyses, which suggested that the parameters substantially affecting cost-effectiveness: were the risk of CRC for individuals with LS; the average number of relatives identified per index patient; the effectiveness of colonoscopy in preventing metachronous CRC; the cost of colonoscopy; the duration of the psychological impact of genetic testing on health-related quality of life (HRQoL); and the impact of prophylactic hysterectomy and bilateral salpingo-oophorectomy on HRQoL (this had the potential to make all testing strategies more expensive and less effective than no testing).LimitationsThe absence of high-quality data for the impact of prophylactic gynaecological surgery and the psychological impact of genetic testing on HRQoL is an acknowledged limitation.ConclusionsResults suggest that reflex testing for LS in newly diagnosed CRC patients aged < 50 years is cost-effective. Such testing may also be cost-effective in newly diagnosed CRC patients aged < 60 or < 70 years. Results are subject to uncertainty due to a number of parameters, for some of which good estimates were not identified. We recommend future research to estimate the cost-effectiveness of testing for LS in individuals with newly diagnosed endometrial or ovarian cancer, and the inclusion of aspirin chemoprevention. Further research is required to accurately estimate the impact of interventions on HRQoL.Study registrationThis study is registered as PROSPERO CRD42012002436.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…34,[59][60][61][62][63][64][65][66][67][68][69][70][71][72] All studies were published between 2000 and 2012 and summary details of each study can be found in Tables 31 and 32.…”

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

Section: Lynch Syndrome Diagnosis-only Studiesmentioning

confidence: 99%

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A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome

Snowsill

Huxley

Hoyle

et al. 2014

Health Technology Assessment

106

234

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Costs and Outcomes of Lynch Syndrome Screening in the Australian Colorectal Cancer Population

Cenin

Naber²,

Lansdorp–Vogelaar³

et al. 2017

Gastroenterology

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Background and Aim: Individuals with Lynch syndrome (LS) are at increased risk of LSrelated cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its costeffectiveness has not been assessed. We aim to determine the cost-effectiveness of screening individuals with CRC for LS at different age-at-diagnosis thresholds. Methods: We developed a decision analysis model to estimate yield and costs of LS screening. Age-specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1-Pathway) or BRAF V600E testing (BRAF-Pathway) if MLH1 expression was lost) for four age-at-diagnosis thresholds-screening < 50, screening < 60, screening < 70, and universal screening. Results: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1-Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF-Pathway identified the same number of LS cases for higher costs. Conclusions: The MLH1-Pathway is more cost-effective than BRAF-Pathway for all ageat-diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.

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Oncología digestiva: genética del cáncer colorrectal

Balaguer

2011

Gastroenterología y Hepatología

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Comparison Between Universal Immunohistochemistry for Mismatch Repair Proteins Versus Revised Bethesda Guidelines in the Detection of Patients With Lynch Syndrome

Cited by 4 publications

References 0 publications

A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome

A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome

Costs and Outcomes of Lynch Syndrome Screening in the Australian Colorectal Cancer Population

Oncología digestiva: genética del cáncer colorrectal

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