Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network

Perrod, Guillaume; Samaha, Elia; Rahmi, Gabriel; Khater, Shérine; Abbès, L.; Savale, Camille; Perkins, Géraldine; Zaanan, Aziz; Châtellier, Gilles; Malamut, Georgia; Cellier, Christophe

doi:10.1177/1756284818775058

Cited by 19 publications

(20 citation statements)

References 29 publications

(57 reference statements)

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“…Geography and differences in follow-up practices might impact cancer risks, although no significant differences were identified in the most recently updated series of the PLSD study, which included 6350 path_MMR carriers who were prospectively observed for 51,646 follow-up years [4]. A recent single centre and retrospective French study suggested that an optimized colonoscopic surveillance program in LS patients might improve screening quality and possibly decrease CRC occurrence, but long-term prospective studies are needed to confirm these findings [5].…”

Section: Introductionmentioning

confidence: 99%

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Dominguez‐Valentin

Seppälä

Sampson

et al. 2019

Hered Cancer Clin Pract

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Background We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5–2.5, 2.5–3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.

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Section: Introductionmentioning

confidence: 99%

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Dominguez‐Valentin

Seppälä

Sampson

et al. 2019

Hered Cancer Clin Pract

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“…Adherence to recommended surveillance in Lynch syndrome has been described in 41%–68% of individuals . We found that 57% of the time at risk was spent within recommended surveillance intervals for individuals at risk of first colorectal cancer.…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2020

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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.

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“…In fact, ADR has been shown to inversely correlate with the risk of incident cancer. 75 Another randomized controlled study analyzing neoplasia detection rates in LS at baseline and follow-up colonoscopy did not find a significant added value for chromoendoscopy over high-definition…”

Section: Performance Of Colonoscopy For Crc Prevention In the Genermentioning

confidence: 96%

The “unnatural” history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance

Ahadova

Seppälä

Engel

et al. 2020

Intl Journal of Cancer

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Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.

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Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network

Cited by 19 publications

References 29 publications

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

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

The “unnatural” history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance

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