Distinct clinical characteristics in stage III rectal cancer among different age groups and treatment outcomes after neoadjuvant chemoradiotherapy

Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633–4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720–5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102–4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145–4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113–2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150–3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745–4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282–3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS ( p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS ( p = 0.006, p = 0.018, p = 0.006, respectively). Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.