Comparative analysis of sporadic, IBD-associated, early-onset and late-onset colorectal cancer: a systematic review and meta-analysis

Background: Colorectal cancer (CRC) remains a multifaceted disease with variations in aetiology, clinical presentation and prognostic factors. Objectives: This study explores the features and outcomes of sporadic (S-CRC), inflammatory bowel disease-associated CRC (IBD-CRC), early-onset CRC (EO-CRC) and late-onset CRC (LO-CRC). Design: This is a systematic review and meta-analysis performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement, comparing S-CRC versus IBD-CRC and EO-CRC versus LO-CRC. Data sources and methods: The literature search was conducted on PubMed and Embase databases. The primary endpoint was the overall 5-year survival rate of CRC. Secondary aims included the features of CRC at diagnosis. Results: Fifty studies and 6,148,851 patients with CRC were included in the analysis. Comparing S-CRC and IBD-CRC, the overall survival was higher in S-CRC (61.88 (range 41.3-78.7) vs 55.54 (51.9-80.9) months). IBD-CRC showed a minor mean age of diagnosis (63.5 (45-78) vs 69.1 ((40-78) years), a minor risk of stage IV (odd ratio (OR) 1.091; 95%CI 1.031-1.155, p = 0.003, I 2 60.24%), higher risk of mucinous tumour (OR 3.150 95%CI 2.797-3.548, p < 0.001, I 2 96.56%), emergency diagnosis (OR 1.598, 95%CI 1.509-1.693, p < 0.001, I 2 77.40%), and synchronous neoplasia (OR 1.942 95%CI 1.705-2.211, p < 0.001, I 2 0.00%). Comparing EO-CRC and LO-CRC, OS was longer in EO-CRC (79.42 (54-96) vs 77.58 (32-92) months). EO-CRC had a higher risk of being diagnosed at stage IV (OR 1.471, 95%CI 1.456-1.486, p < 0.001, I 2 97.12%), and of having mucinous tumours (OR 1.0142, 95%CI 1.015-1.070, p = 0.002, I 2 60.48%) versus LO-CRC. Comparing IBD-CRC, EO-CRC and LO-CRC, IBD-CRC had the shortest OS (61.88 months), the highest rate of mucinous cancer (13%) and emergency diagnosis (24%), whereas metastatic disease at diagnosis was more common in EO-CRC (22.6%). Conclusion: IBD-CRC was associated with a younger mean age at diagnosis, higher risk of mucinous cancers, emergency presentation, and synchronous neoplasia compared to S-CRC. EO-CRC had a higher risk of being diagnosed at stage IV and of mucinous tumours versus LO-CRC. IBD-CRC seemed to have an overall shorter survival rate and a higher prevalence of mucinous cancers, suggesting different pathways of progression and more aggressive features. Trial registration: Prospero Registration ID1021182.