Prognosis of early-onset versus late-onset sporadic colorectal cancer: Systematic review and meta-analysis.

Abstract

Background: In the last years, a dramatic increase in colorectal cancer (CRC) diagnoses in early-onset (EO) patients has been observed. The prognosis of EO-CRC compared to late-onset (LO) patients is still unclear. This meta-analysis aims to clarify whether there is any difference in the prognosis between the two groups.

Methods: A systematic review was conducted on EMBASE-Medline, Pubmed and Cochrane Library in March 2024 to identify studies comparing overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR) and distant recurrence (DR) risk outcomes between EO-CRC (<50 years old) and LO-CRC (>50 years old) with at least 50 patients per group and one year of follow-up. The risk of bias was assessed with the ROBINS-E tool. Data from stage prevalence and survival were extracted and meta-analysed. Meta-regression was used to identify impacting effect modifiers. The PROSPERO registration number was CRD42024573264.

Results: Twenty-six studies were identified; 1,062,037 patients (13.4% EO-CRC and 86.6% LO-CRC) were included in the stage prevalence and 567,689 in the prognostic meta-analysis. Overall, 60% of the EO-CRC and 49% of the LO-CRC were diagnosed with an advanced stage (III-IV) of disease (RR 1.26, 95%CI 1.19-1.35, I²=87%). EO-CRC had a better OS than LO-CRC (HR 0.89, 95%CI 0.81-0.99, I²=89%) but equal CSS (HR 0.94, 95%CI 0.83-1.06, I²=82%), DFS (HR 1.05 95%CI 0.94-1.16, I²=76%), LR (HR 1.41, 95%CI 0.62-3.18, I²=49%) and DR (HR 1.51, 95%CI 0.79-2.89) risk. Meta-regression analysis identified a worse DFS in the EO-CRC rectal cancer subgroup (HR 1.14, 95%CI 1.00-1.30, I²=0%).

Conclusions: Despite the high heterogeneity of existing studies, EO-CRC patients are diagnosed with significantly more advanced stages than LO-CRC, although this is not reflected in any difference in cancer-related survival. There is an urgent need for increased vigilance in the early detection of CRC in young patients.