Impact of Neoadjuvant Chemotherapy Vs. Upfront Surgery on Survival in Early-Onset Colorectal Cancer-a Single Centre Experience.

BACKGROUND:Early-onset colorectal cancer (EO-CRC) has been gaining momentum in the oncologic community and has a reputation for being overtreated. Neoadjuvant therapy has been proven to be an effective treatment for rectal cancers; however, treatment outcomes in this group have yet to be studied. The purpose of this study was to compare overall survival (OS) between the upfront surgery (UFS) group and the neoadjuvant chemotherapy (NAC) group in EO-CRC. METHODS:A retrospective analysis was conducted on 162 patients with stage III-IV locally advanced EO-CRC who underwent radical surgery at a single centre between January 2018 and December 2023. Baseline characteristics, treatment modalities, pathological findings, metastasis, recurrence and survival outcomes, disease-free survival (DFS) and OS, were compared. Survival was assessed using Kaplan-Meier analysis and Cox regression. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS:Baseline demographics were broadly similar except for higher abdominal pain frequency in UFS (42.1% vs. 17.2%, P=0.01). NAC was associated with greater rectal tumor proportion (75.9% vs. 43.6%, P=0.002) and higher pathological downstaging after matching (23/45 vs. 22/45, P=0.001). Survival analyses revealed improved DFS (P=0.005) and OS (P=0.001) with NAC, along with reduced recurrence (P=0.001). Multivariate analysis identified preoperative stage, nodal status, invasion, and metastases as key survival predictors; NAC was not an independent predictor. CONCLUSIONS:In EO-CRC, NAC achieves tumour downstaging and survival benefits compared to UFS. These findings support the integration of NAC into multimodal treatment strategies to improve oncologic outcomes in selected patients. Larger prospective studies are needed.