Missing the Target: Over- and under-diagnosis and over-treatment in Lynch syndrome patients

Toni Seppälä

Helsinki University Hospital, Helsinki, Finland. Johns Hopkins Hospital, Baltimore, USA


The efficacy of colonoscopy surveillance for reducing mortality and incidence of colorectal cancer (CRC) compared to no surveillance has been shown in controlled clinical studies. However, large prospective consortium’s, such as Prospective Lynch Syndrome Database and 3-country-study, have questioned the preventive long-term effectiveness of colonoscopy surveillance in the healthcare setting. Prospective lifetime risk estimates for path_MLH1 and path_MSH2 carriers indicate that up to half of the individuals under surveillance develop CRC despite repeated colonoscopies. Prospectively observed cancer risk differs substantially between the MMR gene affected and possibly variants in question. The prospective studies have not shown benefit of very frequent colonoscopies in terms of decreased CRC incidence, lowered AICC/UJCC stage or overall survival compared to 3-yearly colonoscopies, although randomised controlled trials are lacking. Evidence supporting other measures of cancer screening for cancers in other organs is largely lacking.


Nevertheless, international clinical management guidelines recommend the same colorectal surveillance intervals, the same early age of initiation, and even the same surgical approach for all path_MMR carriers. The current guidelines expose path_MMR carriers to known and unknown harms and risks of repeated colonoscopies and sub-optimally planned surgery without clear evidence of benefit. Updated cost efficiency calculations are warranted to decide on meaningful use of healthcare resources. Clinical Gastroenterology guidelines are in urgent need of revising according to age, gene and gender.


The recent results from the Prospective Lynch Syndrome Database are presented. Possible and observed outcomes of colorectal over-diagnosis are discussed. Under-diagnosis of extra-colorectal and extra-endometrial cancers is discussed.