Clinical characteristics and outcomes in patients with early-onset locally advanced rectal cancer

Background: The incidence of early-onset colorectal cancer (EO-CRC), defined as a diagnosis before 50 years of age, is increasing worldwide. However, its clinical characteristics and outcomes compared to average-onset colorectal cancer (AO-CRC) remain under debate, especially in the setting of locally advanced rectal cancer (LARC). Objectives: This study aimed to compare clinical characteristics, treatment responses, and survival outcomes between patients with early-onset and average-onset locally advanced rectal cancer. Design: A multicenter retrospective cohort study. Methods: We retrospectively analysed 305 patients with stage II-III rectal cancer treated between 2012 and 2022 across three Italian oncology centrers. Patients were categorised as EO-RC (⩽50 years) or AO-RC (>50 years). All patients underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision. Pathological and radiological responses were evaluated, and survival outcomes were assessed through Kaplan-Meier methods. Results: Early-onset patients accounted for 10.5% of the cohort. Clinical and pathological characteristics were broadly similar between groups, although EO-RC patients had a higher prevalence of proficient mismatch repair status. Radiological and pathological response rates were comparable. After a median follow-up of 120 months, the 10-year overall survival (OS) was 73.3% in EO-RC and 91.9% in AO-RC (HR 7.60, 95% CI 2.22-26.06; p = 0.0012). Disease-free survival (DFS) at 10 years was 57.1% in EO-RC and 70.9% in AO-RC (HR 1.80, 95% CI 0.86-3.78; p = 0.1177). Conclusion: Early-onset rectal cancer patients exhibit similar response rates and DFS compared to older patients, but appear to have worse OS. Further studies are needed to explore biological factors and post-recurrence treatment strategies that may influence these outcomes.