Efficacy of Neoadjuvant Hypofractionated Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer: A Single-Center Retrospective Analysis

<b>Background/Objectives</b>: The application of long-course chemoradiotherapy (LCRT) in elderly patients with locally advanced rectal cancer (LARC) can be challenging due to increased risks of complications associated with comorbidities and reduced functional status. This study aimed to assess the efficacy of neoadjuvant hypofractionated chemoradiotherapy (HCRT) in elderly patients with mid-to-low LARC. <b>Methods</b>: We performed a retrospective review of patients diagnosed with LARC from January 2013 to December 2020 and included those aged 70 years or older. Patients were categorized into three groups based on their treatment strategies: neoadjuvant HCRT (33 or 35 Gy in 10 fractions), neoadjuvant LCRT, and upfront surgery. Comparative analyses were performed on clinicopathological characteristics, short-term outcomes, and long-term survival outcomes among these groups. <b>Results</b>: Among the 296 patients included, 30 (10.1%) received HCRT, 195 (65.9%) underwent standard LCRT, and 71 (24.0%) underwent upfront surgery. The baseline characteristics showed that the HCRT group had a higher American Society of Anesthesiologists (ASA) score (ASA score 3 or 4, HCRT 43.3% vs. LCRT 16.9% vs. upfront surgery 15.5%, <i>p</i> = 0.002). The HCRT group showed a significantly lower incidence of radiotherapy-related complications than the LCRT group (16.7% vs. 48.7%, <i>p</i> = 0.001). However, the rate of pathological complete response was significantly lower in the HCRT group (10.0% vs. 15.4%, <i>p</i> = 0.002). The 3-year relapse-free survival (83.0% vs. 77.2% vs. 83.2%; <i>p</i> = 0.411), 3-year local recurrence-free survival (93.1% vs. 93.2% vs. 93.5%; <i>p</i> = 0.464), and 5-year overall survival (65.1% vs. 67.0% vs. 67.7%; <i>p</i> = 0.682) were not significantly different between the three groups. Multivariate analysis also showed that the treatment strategy was not associated with survival outcomes. <b>Conclusions</b>: Neoadjuvant HCRT demonstrated reduced radiotherapy-related complications and acceptable long-term oncologic outcomes. Therefore, neoadjuvant HCRT may be considered as a viable alternative for elderly patients with LARC.