No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies

Engel, Christoph; Vasen, Hans F. A.; Seppälä, Toni T.; Aretz, Stefan; Bigirwamungu-Bargeman, Marloes; Boer, S. Y. De; Bucksch, Karolin; Büttner, Reinhard; Holinski‐Feder, Elke; Holzapfel, Stefanie; Hüneburg, Robert; Jacobs, Maarten; Järvinen, Heikki; Kloor, Matthias; Doeberitz, Magnus von Knebel; Koornstra, Jan J.; Kouwen, Mariëtte van; Langers, Alexandra M. J.; Meeberg, Paul C. van de; Morak, Monika; Möslein, Gabriela; Nagengast, Fokko M.; Pylvänäinen, Kirsi; Rahner, Nils; Renkonen–Sinisalo, Laura; Sanduleanu, Silvia; Schackert, Hans K.; Schmiegel, Wolff; Schulmann, Karsten; Steinke‐Lange, Verena; Strassburg, Christian P.; Vecht, J. van der; Verhulst, M. L.; Cappel, Wouter de Vos tot Nederveen; Zachariae, Silke; Mecklin∥, Jukka–Pekka; Loeffler, Markus

doi:10.1053/j.gastro.2018.07.030

Cited by 113 publications

(113 citation statements)

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“…In our surveyed subsets, stage distribution was favourable, although not statistically significant, with no observation of Stage IV cancers, in contrast to patients who did not undergo surveillance. A favourable stage distribution from colonoscopic surveillance has been suggested in previous studies, although our observations did not reach statistical significance . Improved survival has been associated with surveillance although conflicting results have been reported in other studies .…”

Section: Discussioncontrasting

confidence: 78%

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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Section: Discussioncontrasting

confidence: 78%

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

et al. 2020

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“…We found that 2‐yearly colonoscopic surveillance was more cost‐effective than annual surveillance, while assuming that CRC incidence is reduced a further 10% by annual surveillance compared with 2‐yearly surveillance. Recent studies found no statistically significant differences by surveillance interval in cumulative CRC incidence or CRC stage at diagnosis in people with LS . Ongoing quality colonoscopy is required to maximise the benefits of any strategy.…”

Section: Discussionmentioning

confidence: 99%

The predicted impact and cost‐effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome

Kang

Killen

Caruana

et al. 2019

Medical Journal of Australia

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Objectives:To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia.Design, setting, participants: We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance. Main outcome measures:Cost-effectiveness of six universal tumour testing strategies (testing for DNA mismatch repair deficiencies) and of universal germline gene panel testing of patients with incident CRC; impact on cost-effectiveness of restricting testing by age at CRC diagnosis (all ages, under 50/60/70 years) and of colonoscopic surveillance interval (one, two years). Results:The cost-effectiveness ratio of universal tumour testing strategies (annual colonoscopic surveillance, no testing age limit) compared with no testing ranged from $28 915 to $31 904/life-year saved (LYS) (indicative willingness-to-pay threshold: $30 000-$50 000/LYS). These strategies could avert 184-189 CRC deaths with an additional 30 597-31 084 colonoscopies over the lifetimes of 1000 patients with incident CRC with LS and 1420 confirmed LS carrier relatives (164-166 additional colonoscopies/death averted). The most cost-effective strategy was immunohistochemistry and BRAF V600E testing (incremental cost-effectiveness ratio [ICER], $28 915/LYS). Universal germline gene panel testing was not costeffective compared with universal tumour testing strategies (ICER, $2.4 million/LYS). Immunohistochemistry and BRAF V600E testing was cost-effective at all age limits when paired with 2-yearly colonoscopic surveillance (ICER, $11 525-$32 153/LYS), and required 4778-15 860 additional colonoscopies to avert 46-181 CRC deaths (88-103 additional colonoscopies/death averted). Conclusions:Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective.The known: Testing people with colorectal cancer for Lynch syndrome has been found to be cost-effective in some developed countries.The new: In the first Australian cost-effectiveness evaluation of systematic testing for Lynch syndrome in people with incident colorectal cancer that included all feasible combinations of relevant testing and triage options, the cost-effectiveness ratios for universal tumour testing strategies for identifying mismatch repair deficiency (dMMR), compared with not testing, were similar. Universal gene panel testing was not cost-effective compared with universal tumour testing strategies.The implications: Our analysis supports routine dMMR tumour testing of people with incident colorectal ...

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“…[5][6][7] Recent data from Europe demonstrate a 10-year cumulative CRC incidence of up to 18.4% in patients undergoing close colonoscopic surveillance. 8 Surprisingly, no difference in the incidence or stage of CRC was observed between countries with an annual, versus 1-year to 2year, or 2-year to 3-year, surveillance interval. These data question the necessity of annual colonoscopy in all LS patients and call for further research to understand the limitations of colonoscopy and the biology of CRC development.…”

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confidence: 88%

Enhancing the efficacy of colonoscopy in Lynch syndrome: the search for the holy grail continues

Mankaney¹,

Burke²

2019

Gastrointestinal Endoscopy

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share the results from their randomized controlled trial assessing the impact of proximal colon chromoendoscopy for the detection of neoplasia at baseline and follow-up colonoscopy in patients with Lynch syndrome (LS) performed across 6 centers in the Netherlands. In the trial, indigo carmine chromoendoscopy application in the proximal colon was compared with standard white-light endoscopy (WLE) in 246 mismatch repair gene mutation carriers. Although chromoendoscopy led to a significantly increased median withdrawal time (19 vs 12 minutes), no improvement in the number of patients detected with neoplasia was observed (30% vs 27%). In a subgroup analysis, chromoendoscopy was not associated with the detection of proximal adenomas (24% vs 16%) but more than doubled the detection of "nuisance" lesions (56% vs 26%), including polypoid normal mucosa and lymphoid follicles. At the end of the study, one quarter of the study patients were excluded, and end-of-study colonoscopy was performed in only 186 patients at a median of 2 years after the baseline examination. At that time, the included patients had their proximal colons again sprayed with chromoendoscopy. No difference was noted in the overall rate of neoplasia detection (26% vs 28%) or in neoplasms detected per colonoscopy (0.39 vs 0.41). Subgroup analysis of findings in the proximal colon also yielded no significant differences. The proximal adenoma detection rate (ADR) was 22% in each arm. Importantly, colorectal cancer (CRC) was diagnosed at the 2-year colonoscopy in 4 patients (2.1%); 3 in the chromoendoscopy at baseline group, and 1 in the WLE at baseline group.LS is a hereditary cancer risk predisposition syndrome due to defective DNA mismatch repair (MMR). The diagnosis is made in a patient by the detection of a germline pathogenic variant in 1 of the MMR genes (MLH1, MSH2, MSH6, PMS2) or EPCAM. Data demonstrate that the cumulative risk of CRC by age 70 varies by mutation and gender. Risks are lower in women than in men, lowest in those with a PMS2 mutation, intermediate in those with MSH6, and highest in those with MLH1 and MSH2 pathogenic mutation carriers. CRC risk derived from studies excluding PMS2 and accounting for ascertainment bias demonstrate cumulative risks ranging between 27% and 45% for men and between 22% and 38% for women. 2 Guidelines recommend surveillance colonoscopy every 1 to 2 years starting at ages 20 to 25, or 2 to 5 years before the earliest CRC in the family if diagnosed before age 25. 3,4 The frequent surveillance intervals suggested are due to reported rates of rapid development of advanced neoplasia and CRC, particularly in the proximal colon and occurring within 2 to 3 years of previous colonoscopy. [5][6][7] Recent data from Europe demonstrate a 10-year cumulative CRC incidence of up to 18.4% in patients undergoing close colonoscopic surveillance. 8 Surprisingly, no difference in the incidence or stage of CRC was observed between countries with an annual, versus 1-year to 2year, or 2-year to 3-year, surveillance interval. These...

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No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies

Cited by 113 publications

References 35 publications

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

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

The predicted impact and cost‐effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome

Enhancing the efficacy of colonoscopy in Lynch syndrome: the search for the holy grail continues

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