Risk factors for metachronous colorectal cancer and advanced neoplasia following primary colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Identifying risk factors for metachronous colorectal cancer (CRC) and metachronous advanced neoplasia could be useful for guiding surveillance. We conducted a systematic review and meta-analysis to investigate risk factors for metachronous CRC and advanced neoplasia. METHODS: Searches were conducted in MEDLINE, Embase, Web of Science and Cochrane Central Registry of Controlled Trials for articles (searching period: 1945 to Feburary, 2021) that reported the results of an association between any factor and metachronous advanced neoplasia or metachronous CRC. There were no restrictions on the publication date or language. Random effects models were fitted to estimate the combined association between the risk factors and metachronous CRC or advanced neoplasia. The Risk of Bias In Non-Randomised Studies of Interventions tool (ROBINS-I) was used to assess the risk of bias of included studies. RESULTS: In total, 22 observational studies with 625,208 participants were included in the systematic review and meta-analysis. Of these, 13 studies investigated risk factors for metachronous CRC and 9 for advanced neoplasia. The risks of metachronous CRC or advanced neoplasia were higher if the first CRC was diagnosed in the presence of a synchronous advanced lesion (pooled risk ratio (RR) from 3 studies: 3.61, 95% confidence interval (CI): 1.44-9.05; and pooled RR from 8 studies: 2.77, 95% CI: 2.23-3.43, respectively). The risk of metachronous CRC was lower, but the risk of metachronous advanced neoplasia was higher if the first CRC was distal (compared with proximal) (pooled RR from 3 studies: 0.48, 95% CI: 0.23-0.98; and pooled RR from 2 studies: 2.99, 95% CI: 1.60-5.58 respectively). The risk of metachronous advanced neoplasia increased with age (pooled RR from 3 studies: 1.07 per year of age, 95% CI: 1.03-1.11). There was no evidence that any lifestyle risk factors studied were associated with the risk of metachronous CRC or advanced neoplasia. CONCLUSIONS: The identified risk factors for metachronous CRC and advanced neoplasia might be useful to tailor the existing surveillance guidelines after the first CRC. There were potential limitations due to possible misclassification of the outcome, confounding and risk of bias, and the findings cannot be generalised to high-risk genetic syndrome cases.