Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases

Background Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). Methods We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high through-put coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs. Results Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p<0.0005). The majority of incident cancers (21/28) were detected after previous colonoscopy without any pathological findings. On the molecular level, incident cancers presented with a significantly lower KRAS codon 12/13 (1/23, 4.3% vs. 11/21, 52%; p=0.0005) and pathogenic TP53 mutation frequency (0/17, 0% vs. 7/21, 33.3%; p=0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating APC mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. The proportion of MMR deficiency-related mutational events was significantly higher in incident compared to prevalent CRC (p=0.018). Conclusions LS CRC diagnosed under regular colonoscopy surveillance are biologically distinct, suggesting that the preventive effectiveness of colonoscopy in LS depends on the molecular subtypes of tumors.

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Cost-Effectiveness of the Manchester Approach to Identifying Lynch Syndrome in Women with Endometrial Cancer

Journal of Clinical Medicine ◽

10.3390/jcm9061664 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1664 ◽

Cited By ~ 2

Author(s):

Tristan M. Snowsill ◽

Neil A. J. Ryan ◽

Emma J. Crosbie

Keyword(s):

Endometrial Cancer ◽

Cost Effectiveness ◽

Lynch Syndrome ◽

Cancer Patients ◽

Cost Effective ◽

Hereditary Cancer Syndrome ◽

Cancer Syndrome ◽

Universal Testing ◽

Life Years

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy.

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