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

• Published in: European journal of cancer (1990) 2024-12, Vol.215, p.115172, Article 115172
• Main Authors: Carbone, Fabio, Spinelli, Antonino, Ciardiello, Davide, Luc, Marco Realis, de Pascale, Stefano, Bertani, Emilio, Fazio, Nicola, Romario, Uberto Fumagalli
• Format: Article
• Language: English
• Subjects: Colorectal cancer; early-onset; epidemiology; late-onset; meta-analysis; rectal cancer
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.115172

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. 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) 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. 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, p=0.41, 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%). 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. •60% of early-onset (EO) colorectal cancers (CRC) are diagnosed at an advanced stage•EO-CRC has better overall survival but equal cancer-specific survival than late-onset•EO rectal cancer patients may have worse disease-free survival than late-onset