Background: The treatment of locally advanced rectal cancer (LARC) in older patients is not sufficiently standardized in international guidelines. Short-course radiotherapy (SCRT) followed by delayed surgery has emerged as a promising therapeutic option for these patients, offering potential benefits in terms of reduced treatment time and toxicity, along with improved convenience. Materials and Methods: From February 2019 to April 2024, a total of 141 older patients aged ≥ 70 years [median age = 79 (range, 70–91)], unfit for chemotherapy and with LARC (stage II-III) adenocarcinoma, underwent SCRT (5 daily fractions of 5 Gy each for a total dose of 25 Gy) followed by delayed surgery (no earlier than 6 weeks after the end of treatment). The study was conducted at 11 centers in Italy. Down-staging rates, relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), safety, and mortality were analyzed. Results: Down-staging occurred in 87 cases (61.7 %). Complete radiological responses after SCRT and before surgery were reported in 10 patients (7.1 %), while partial responses were reported in 77 (54.6 %) cases. All patients underwent delayed surgery. The R0 resection rate was 93.6 %. Eight patients (5.7 %) had a pathological complete response (pCR). At a follow-up of 70.5 months, the median RFS, OS and CSS were 31.5, 40.5 and 41.5 months, respectively. Post-operative severe morbidity was 23.4 %, and mortality was 2.8 %. Conclusions: Overall, SCRT offers a viable alternative to conventional long-term radiotherapy plus chemotherapy in older patients with LARC, with favorable results in terms of efficacy, limited toxicity and low mortality.
