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Risk factors for metachronous colorectal cancer in Lynch syndrome patients: a registry-based observational mono-institutional study cohort

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Abstract

Background

Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection.

Methods

Patient’s clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan–Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated.

Results

In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively).

Conclusions

Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development.

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Acknowledgements

The authors wish to acknowledge and express sincere gratitude to Mariangela Di Ceglie and Ornella Galuppo from the Hereditary Digestive Tract Tumors Unit, for prospectively maintaining patient’s database.

Funding

No funding was received.

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Author notes

  1. Stefano Signoroni and Guglielmo Niccolò Piozzi contributed equally as co-first authors.

Authors and Affiliations

  1. Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy

    Stefano Signoroni, Maria Teresa Ricci, Lucio Bertario & Marco Vitellaro

  2. Colorectal Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy

    Guglielmo Niccolò Piozzi & Marco Vitellaro

  3. Diagnostic and Surgical Endoscopy Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy

    Andrea Mancini

  4. Medical Statistics Unit, University of Milan, via Festa del Perdono, 7, 20122, Milan, Italy

    Alberto Morabito

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  1. Stefano Signoroni
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  2. Guglielmo Niccolò Piozzi
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  3. Maria Teresa Ricci
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Correspondence to Stefano Signoroni.

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Alberto Morabito and Lucio Bertario are Retired from July 2014.

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Signoroni, S., Piozzi, G.N., Ricci, M.T. et al. Risk factors for metachronous colorectal cancer in Lynch syndrome patients: a registry-based observational mono-institutional study cohort. Int J Clin Oncol 25, 1644–1652 (2020). https://doi.org/10.1007/s10147-020-01700-2

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  • DOI: https://doi.org/10.1007/s10147-020-01700-2

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