Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals

Julia Steinberg¹, Priscilla Chan², Emily Hogden², Gabriella Tiernan², April Morrow², Yoon-Jung Kang², Emily He², Rebecca Venchiarutti³, Leanna Titterton⁴, Lucien Sankey⁵, Amy Pearn⁶, Cassandra Nichols⁷, Skye McKay², Anne Hayward⁸, Natasha Egoroff⁹, Alexander Engel¹⁰, Peter Gibbs¹¹, Annabel Goodwin¹², Marion Harris⁵, James G Kench^{13

14}, Nicholas Pachter^{7

15}, Bonny Parkinson¹⁶, Peter Pockney⁹, Abiramy Ragunathan¹⁷, Courtney Smyth⁵, Michael Solomon^{14

18}, Daniel Steffens^{3

18}, James Wei Tatt Toh¹⁹, Marina Wallace²⁰, Karen Canfell², Anthony Gill²¹, Finlay Macrae²², Kathy Tucker^{23

24}, Natalie Taylor^{2

25}

Affiliations

¹ The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, 153 Dowling St, NSW, 2011, Woolloomooloo, Australia. julia.steinberg@nswcc.org.au.
² The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, 153 Dowling St, NSW, 2011, Woolloomooloo, Australia.
³ Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
⁴ NSW Health, Western Sydney Local Health District, Westmead, NSW, Australia.
⁵ Monash Health, Melbourne, Victoria, Australia.
⁶ Cancer Council NSW, Sydney, NSW, Australia.
⁷ Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia.
⁸ The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁹ School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
¹⁰ The University of Sydney, Northern Clinical School Royal North Shore Hospital, Sydney, NSW, Australia.
¹¹ Personalised Oncology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
¹² Cancer Genetics Department, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹³ Department of Tissue Pathology & Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
¹⁵ School of Medicine and Pharmacology, University of Western Australia, Perth, Western, Australia.
¹⁶ Centre for the Health Economy, Macquarie University, Sydney, NSW, Australia.
¹⁷ Westmead Familial Cancer Services, The Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
¹⁸ Department of Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹⁹ Department of Colorectal Surgery, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia.
²⁰ Fiona Stanley Hospital, South Metropolitan Health Service, Murdoch, Western Australia, Australia.
²¹ Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
²² Colorectal Medicine and Genetics, Department of Medicine, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
²³ Hereditary Cancer Clinic, Prince of Wales Hospital, Sydney, NSW, Australia.
²⁴ Prince of Wales Clinical School, UNSW, Sydney, NSW, Australia.
²⁵ School of Population Health, Faculty of Medicine, UNSW, Sydney, NSW, Australia.

PMID: 35509103
PMCID: PMC9066828
DOI: 10.1186/s13053-022-00225-1

Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals

Julia Steinberg et al. Hered Cancer Clin Pract. 2022.

. 2022 May 4;20(1):18.

doi: 10.1186/s13053-022-00225-1.

Authors

Affiliations

¹ The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, 153 Dowling St, NSW, 2011, Woolloomooloo, Australia. julia.steinberg@nswcc.org.au.
² The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, 153 Dowling St, NSW, 2011, Woolloomooloo, Australia.
³ Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
⁴ NSW Health, Western Sydney Local Health District, Westmead, NSW, Australia.
⁵ Monash Health, Melbourne, Victoria, Australia.
⁶ Cancer Council NSW, Sydney, NSW, Australia.
⁷ Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia.
⁸ The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁹ School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
¹⁰ The University of Sydney, Northern Clinical School Royal North Shore Hospital, Sydney, NSW, Australia.
¹¹ Personalised Oncology Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
¹² Cancer Genetics Department, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹³ Department of Tissue Pathology & Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
¹⁵ School of Medicine and Pharmacology, University of Western Australia, Perth, Western, Australia.
¹⁶ Centre for the Health Economy, Macquarie University, Sydney, NSW, Australia.
¹⁷ Westmead Familial Cancer Services, The Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
¹⁸ Department of Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
¹⁹ Department of Colorectal Surgery, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia.
²⁰ Fiona Stanley Hospital, South Metropolitan Health Service, Murdoch, Western Australia, Australia.
²¹ Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
²² Colorectal Medicine and Genetics, Department of Medicine, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
²³ Hereditary Cancer Clinic, Prince of Wales Hospital, Sydney, NSW, Australia.
²⁴ Prince of Wales Clinical School, UNSW, Sydney, NSW, Australia.
²⁵ School of Population Health, Faculty of Medicine, UNSW, Sydney, NSW, Australia.

PMID: 35509103
PMCID: PMC9066828
DOI: 10.1186/s13053-022-00225-1

Abstract

Background: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states.

Methods: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals.

Results: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients).

Conclusions: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

Keywords: Bottleneck; Gap; Genetics services referral; Heterogeneity in practice; Lynch syndrome; Medical records; Mismatch repair; Tumour testing.

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Conflict of interest statement

KC is co-PI of unrelated investigator-initiated trial of cervical screening in Australia (‘Compass’) conducted by the Victorian Cytology Service, which has received funding contribution from Roche Molecular Systems and Ventana, USA. The other authors declare no potential conflicts of interest.

Figures

**Fig. 1**
LS tumour testing and referral to genetics services at seven Australian hospitals in 2017–2018. The percentages in each box are calculated relative to the number of patients in the previous testing step. The numbers of patients with (i) MSH2 or MSH6 loss, or (ii) PMS2 loss only, together account for < 10 patients per hospital and are not shown separately to protect patient confidentiality. * test used for at least some patients

**Fig. 2**
dMMR/MSI test results and referral to genetics services by patient age group. a dMMR/MSI tumours were more common in older patients (Wilcoxon p = 3.7 × 10^− 13 for difference in ages of patients with and without dMMR/MSI). b Older patients with tumour test results complete and indicating high LS risk were less likely to be referred to genetics services (Wilcoxon p = 9.8 × 10^− 5 for difference in ages of patients with and without referral record)

See this image and copyright information in PMC

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Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals

Affiliations

Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous