Structured surveillance in Lynch syndrome: effectiveness, limitations, and unmet needs

Abstract

Background

Lynch syndrome confers a high lifetime risk of multiorgan cancers. Although colorectal surveillance is well established, prospective data on cancer incidence and adherence to structured multiorgan follow-up and surveillance recommendations remain limited.

Materials and methods

We retrospectively analyzed prospectively collected data from 517 individuals carrying a pathogenic or likely pathogenic variant in a mismatch repair gene at a single specialized French center. All patients underwent structured surveillance, including regular colonoscopy and organ-specific follow-up according to national guidelines. Cancer incidence rates, tumor distribution, and modes of detection (asymptomatic versus symptomatic) were assessed over the follow-up.

Results

Over 4827 person-years, 201 cancers were diagnosed (annual cancer incidence 4.16%, 95% confidence interval 3.59-4.74). Colorectal cancer was most frequent (41.8%), followed by urinary tract (11.9%) and skin cancers. Among guideline-surveilled organs (n = 132), most were detected asymptomatically, particularly lower gastrointestinal (GI) (84.5%) and urinary tract (85%) cancers, whereas >50% of upper GI cancers were diagnosed symptomatically. Gynecologic cancers were rare, likely reflecting prophylactic surgery. Notably, 69 cancers (34%) arose outside guideline-recommended surveillance organs, primarily skin, breast, prostate, and pancreas. Cancer-specific mortality was lower among the cancers detected under surveillance, although this difference did not reach statistical significance.

Conclusions

Despite structured, multiorgan surveillance, patients with Lynch syndrome exhibit high cancer incidence and broad tumor distribution. Although current protocols enable early detection for several organs, a substantial proportion of cancers occur outside existing recommendations. These findings support follow-up in dedicated coordination centers and may inform the selective expansion of surveillance strategies to additional high-risk organs.