Screening for Lynch syndrome less effective at older ages, study finds

Lynch syndrome is rare after age 80 years, making the efficiency of universal screening very low, so stopping reflex screening in this age group may be reasonable, particularly in resource-limited settings, the study authors said.


The efficacy of screening for Lynch syndrome in patients with newly diagnosed colorectal cancer decreases substantially after age 70 to 75 years, according to a recent study.

Guidelines recommend that all patients with new colorectal cancer diagnoses be screened for Lynch syndrome. To determine the effectiveness of such screening in elderly patients, researchers performed a retrospective cohort study in a large community-based health care system to compare age-restricted and universal screening of colorectal cancer tumors using reflex mismatch repair (MMR) immunohistochemistry (IHC). Results were published June 11 by Annals of Internal Medicine.

The study included 3,891 patients with a new diagnosis of colorectal cancer who were screened for Lynch syndrome between 2011 and 2016. Universal screening identified 63 cases of Lynch syndrome (diagnostic yield, 1.6%), and of these, 28 were age 50 years or younger, 18 were age 51 to 60 years, 12 were age 61 to 70 years, 4 were age 71 to 80 years, and 1 was older than age 80 years. The researchers used all patients with colorectal cancer as the denominator and found that the diagnostic yield increased from 0.72% when 50 years was used as the upper age limit for screening to 1.54% for 75 years and 1.59% for 80 years. With an upper age limit for screening of 75 years, 3 of 63 cases of Lynch syndrome (4.8%) were missed but 1,053 fewer cases (27.1%) required tumor MMR IHC. Using 80 years as the upper limit meant that 1 of 63 cases of Lynch syndrome (1.6%) were missed and that 668 fewer cases (17.2%) required tumor MMR IHC.

The researchers noted that their patients who were eligible for germline analysis but did not complete it were not included in calculations of performance characteristics and that MMR IHC has imperfect sensitivity for detecting Lynch syndrome, among other limitations. They concluded that patient age at diagnosis of colorectal cancer was a key factor influencing the performance of Lynch syndrome screening and that the diagnostic yield decreased markedly after age 70 to 75 years. “Because [Lynch syndrome] is rare after age 80 years, the efficiency of universal screening is very low, and stopping reflex screening in this age group may be reasonable, particularly in resource-limited settings,” the authors wrote. They called for further study in other populations and noted that MMR IHC can still benefit patients with colorectal cancer who need chemotherapy by helping to guide their treatment.