Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome

Abstract

Aim Although patients with Lynch syndrome have an increased risk of developing colorectal cancer, surveillance can reduce morbidity and mortality. Whether or not affected individuals benefit from lifetime surveillance depends on individual factors and patient adherence, and these may vary, complicating risk modelling. The aim of this study was to identify individual factors which influence patient adherence to surveillance programmes and whether extended surveillance interval influenced their risk of developing colorectal cancer.Method Demographics and survival data were obtained from patients (n = 1223) with Lynch syndrome, identified by interrogating the Danish Hereditary Non-Polyposis Colorectal Cancer Register. These data were linked to patient surveillance interval data which had been divided into three subsets (< 27 months, adherent to the recommended biennial programme; > 27 months, extended surveillance interval; and no surveillance) to estimate the cumulative risks and hazard ratios (HRs) for colorectal cancer.Results In all, 147 colorectal cancers (99 first; 48 metachronous) were identified in 1223 patients. Factors associated with adherence to surveillance were female sex, a previous history of cancer and age < 75 years. The cumulative incidence for colorectal cancer was 38% (95% CI 27%-50%) for surveillance intervals < 27 months, 48% (95% CI 29%-67%) for intervals > 27 months and 72% (95% CI 61%-83%) with no surveillance. Adjusted HRs were 0.22 for surveillance intervals < 27 months and 0.32 for surveillance intervals > 27 months. Extended surveillance intervals > 27 months had a nonsignificant benefit with an HR of 1.51 (95% CI 0.83-2.75) compared to surveillance intervals < 27 months.Conclusion This study demonstrates that adherence to colonoscopic surveillance in Lynch syndrome varies with age, sex and cancer history and demonstrates a consistent benefit from colorectal cancer surveillance, though it might be lower for individuals with extended intervals.Keywords Hereditary non-polyposis colorectal cancer, mismatch repair deficiency, colon cancer, complianceWhat does this paper add to the literature? In this paper a time-based model is used to study how extending the length of surveillance intervals affects the development of Lynch-syndrome-associated colorectal cancer. Compared to no surveillance, surveillance intervals > 27 months or < 27 months reduce the risk of developing colorectal cancer 3-fold or 4-fold, respectively.

Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden

“…Colorectal cancer (CRC) is one of the most common cancers in both sexes, and the second leading cause of cancer death in Sweden [ 1 ]. Approximately 3% of CRC cases are attributed to pathogenic variants in mismatch repair genes causing Lynch syndrome [ 2 ], resulting in up to 70% lifetime risk of developing CRC [ 3 ]. Targeted surveillance in high-risk families has been shown to reduce both cancer morbidity and cancer mortality [ 3 , 4 ].…”

“…Approximately 3% of CRC cases are attributed to pathogenic variants in mismatch repair genes causing Lynch syndrome [ 2 ], resulting in up to 70% lifetime risk of developing CRC [ 3 ]. Targeted surveillance in high-risk families has been shown to reduce both cancer morbidity and cancer mortality [ 3 , 4 ]. Additionally, individuals with no detected pathogenic germline variant, but doubled CRC risk (familial CRC) are recommended colonoscopy surveillance.…”

Increased Number of Colorectal Interval Cancers in Lynch Syndrome after the SARS-CoV-2 Pandemic: A Survey-Based Study

“…Most diagnosed 1–3 interval cancers, but 8.1% reported up to five interval cancers. This result was likely not the consequence of endoscopy units shutting down because most units resumed endoscopy services shortly after the first wave [ 20 ]. Endoscopic emergencies were still performed (73.3% of cases).…”

The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome

“…We used sex-specific first CRC risk in path_PMS2 heterozygotes from a large international study as a surrogate estimate for first CRC risk without colonoscopic surveillance, which adjusted for the ascertainment bias using a modified segregation analysis. 20 First CRC risks with colonoscopic surveillance at varying intervals We compared the cumulative CRC risk in patients with LS under various colonoscopic surveillance intervals [21][22][23][24][25] and found approximately 2% absolute reduction for every 1-year decrement in the surveillance interval, which is equivalent to decrease in HR by 0.05. 11 Therefore, for every 1-year decrement in the surveillance interval, we assumed that the estimated HR for first CRC incidence in patients with LS undergoing regular surveillance decreased by 0.05 from the fitted HR associated with 3-yearly colonoscopic surveillance (vs no surveillance), while also assuming the same HR across all ages that are surveilled (see Appendix 1.2).…”

“…11 We assumed that metachronous CRC risk does not differ by sex, MMR genes, or individual's age at the time of surgery 11,18,19,26,27 and the effect of colonoscopic surveillance on metachronous CRC incidence is the same regardless of surveillance interval (HR = 0.881) (see Appendix 1.3). 21 We modeled the same CRC stage distribution regardless of surveillance interval because strict annual surveillance did not significantly reduce CRC incidence or early-stage diagnosis (vs 2-or 3yearly). 10 We made a simplifying assumption that CRC diagnosis is made at the time of regular colonoscopy visit (ie, interval cancers were not modeled).…”