Lynch Syndrome Screening Strategies Among Newly Diagnosed Endometrial Cancer Patients

Division of Gynecologic Oncology, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH 43210, USA.
Obstetrics and Gynecology (Impact Factor: 5.18). 10/2009; 114(3):530-6. DOI: 10.1097/AOG.0b013e3181b11ecc
Source: PubMed


To estimate the cost-effectiveness of screening strategies for Lynch syndrome among newly diagnosed endometrial cancer patients.
A decision analysis compared four strategies to screen women with newly diagnosed endometrial cancer for Lynch syndrome: 1) Amsterdam criteria strategy, where full gene sequencing was performed for women who meet Amsterdam criteria; 2) Sequence-all strategy, where full gene sequencing was performed for all women with endometrial cancer; 3) Sequence aged younger than 60 years strategy, where full gene sequencing was performed for women aged younger than 60 years with endometrial cancer; and 4) immunohistochemistry/single gene strategy, where immunohistochemistry was performed for the DNA mismatch repair genes for all women after single gene sequencing for specific women lacking protein expression. Prevalence rates, probabilities of immunohistochemistry staining loss, and gene mutation rates were calculated from published data. Costs were estimated from Medicare reimbursement rates. Cost-effectiveness ratios and incremental cost-effectiveness ratios were estimated for each strategy.
For the estimated 40,000 women diagnosed annually with endometrial cancer, the sequence-all strategy detects 920 patients with Lynch syndrome at a cost of $105 million. The Amsterdam criteria give the least-expensive strategy ($7 million), but detect the fewest patients (n=83) with Lynch syndrome. The immunohistochemistry/single gene sequencing strategy detects 858 patients at a cost of $17 million; this strategy has an incremental cost-effectiveness ratio of $13,812. The sequence aged younger than 60 years strategy was less effective and more costly than other strategies.
Of the strategies studied, immunohistochemical evaluation of tumor specimens for mismatch repair protein expression after single gene sequencing for patients with endometrial cancer is a cost-effective strategy for detecting Lynch syndrome.
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    • "Reflex testing of colorectal tumours, defined as the routine screening of tumours for evidence of defective DNA mismatch repair as a phenotypic marker of LS, has been proposed as a strategy to increase identification of individuals with LS, and represents an emerging standard of care [22, 23]. Two cost effectiveness analyses of reflex testing in newly diagnosed CRC patients and a similar analysis in newly diagnosed endometrial cancer patients have demonstrated that cost effectiveness of such screening is comparable to accepted screening activities in the general population [24–26]. For several reasons, widespread adoption of reflex testing has proven to be a challenge in individual clinical centres, as well as in public health initiatives [27, 28]. "
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    ABSTRACT: The aim of this qualitative study was to examine the experience of individuals facing a choice about genetic counselling/testing in the context of newly diagnosed colorectal cancer (CRC). Nineteen individuals with newly diagnosed CRC, including 12 individuals who accepted genetic counselling ("acceptors") and 7 individuals who declined genetic counselling ("refusers"), were interviewed using a standardized questionnaire guide which focused on motivations and barriers experienced in the decision process. Data were analyzed using Karlsson's Empirical Phenomenological method of data analysis (Karlsson in Psychological qualitative research from a phenomenological perspective. Almgvist and Wiksell International, Stockholm, 1993). Three major themes were identified: facing challenges in health literacy; mapping an unknown territory; and adjusting to cancer. The study participants' testimonies provided novel insights into potential reasons for patient non-engagement in pilot studies of reflex testing for Lynch syndrome, and allowed us to formulate several recommendations for enhancing patient engagement. Our study findings suggest that patient engagement in clinical cancer genetics services, including reflex testing for Lynch syndrome, can only be achieved by addressing current health literacy issues, by deconstructing current misconceptions related to potential abuses of genetic information, by emphasizing the clinical utility of genetic assessment, and by adapting genetics practices to the specific context of cancer care.
    Familial Cancer 09/2013; 13(1). DOI:10.1007/s10689-013-9677-0 · 1.98 Impact Factor
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    • "The method used is often determined by the availability of a test and may be laboratory or institution specific. Cost-effectiveness data regarding Lynch syndrome screening of endometrial tumors also exist, albeit not to the same extent as among colon cancers, suggesting that screening is cost-effective, at least in some circumstances (Kwon et al. 2011; Resnick et al. 2009a). Surveillance recommendations for individuals who are known to carry a mismatch repair gene mutation are significantly different from both general population guidelines and guidelines for individuals with a family history of colorectal cancer (Dove-Edwin et al. 2005). "
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    ABSTRACT: An electronic survey of the National Society of Genetic Counselors Cancer Special Interest Group was conducted in July 2011 to assess Lynch syndrome tumor screening programs and identify barriers to implementation. Over half of respondents (52.8 %) reported having a routine Lynch syndrome tumor screening protocol for newly diagnosed colon and/or endometrial cancers, and approximately half of these used a universal approach. There was an increase in the number of those screening over time, especially in the past 3 years. Tumor screening methods varied; 34/53 (64.2 %) started with immunohistochemistry, 11/53 (20.8 %) started with microsatellite instability testing and 8/53 (15.1 %) performed both on newly diagnosed colorectal tumors. Just 21.7 % (23/106) of respondents indicated they have a tumor screening program in place for newly diagnosed endometrial cancers. Written consent is rarely obtained (7.1 %) and the method of how results were returned to the patient was variable among respondents. Prevalent barriers to implementation were concern about cost, bringing key players together and convincing medical staff of the necessity. Use of Lynch syndrome tumor screening is in clinical practice, but protocols vary widely. This survey provides a glimpse of current practices and common barriers, and identifies the need for tumor screening algorithms with outcomes data.
    Journal of Genetic Counseling 05/2013; 23(1). DOI:10.1007/s10897-013-9603-5 · 2.24 Impact Factor
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    ABSTRACT: Lynch syndrome is a heritable, cancer susceptibility syndrome. This study aims to review current and emerging trends in the identification of Lynch syndrome in the endometrial cancer patient population. We performed a comprehensive review of past and present screening algorithms for Lynch syndrome, including a review of the utility of both the Amsterdam criteria and Bethesda guidelines. Because non-colon cancers have historically not been the focus of Lynch syndrome research, current literature is ripe with questions regarding screening among this patient population. Low BMI, age less than 50, positive family history and pathologic features have all been identified as risk factors in endometrial cancer patients who might benefit from Lynch screening. Additionally, based on experience at our own institution we offer a feasible screening algorithm for these patients. A comprehensive review of the data demonstrated that immunohistochemistry is becoming an efficient, inexpensive way to screen tumors at risk for mismatch repair deficiency. The sensitivity and specificity of immunohistochemistry for predicting Lynch syndrome approaches 100%. Ideally, prospective screening of all endometrial cancer patients with IHC is a feasible, cost-efficient way to detect Lynch in this patient population given the limitations of using personal/family history of malignancy as well as pathologic risk factors. It is imperative that clinicians be mindful of the risk of Lynch syndrome in women with endometrial cancer. Given the opportunity for colon cancer screening and prevention strategies to be initiated, the identification of probands with endometrial cancer as a result of Lynch syndrome will lead to a reduction in morbidity and mortality for these patients and their families.
    Gynecologic Oncology 05/2009; 114(1):128-34. DOI:10.1016/j.ygyno.2009.03.003 · 3.77 Impact Factor
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