Efficacy of long-course versus short-course chemoradiotherapy combined with immunotherapy for pMMR/MSS rectal adenocarcinoma: A real-world cohort study.

Abstract

e15645 Background: The integration of immunotherapy with chemoradiotherapy (CRT) represents a novel therapeutic strategy for pMMR/MSS rectal adenocarcinoma. However, no prospective studies have demonstrated whether long-course radiotherapy (LCRT) or short-course radiotherapy (SCRT) exhibits superior synergistic effects when combined with immunotherapy. This study aims to evaluate the efficacy of SCRT versus LCRT in combination with immunotherapy using real-world data from a single institution and to investigate the differential impact of the two radiotherapy modalities on immunotherapy sensitization. Methods: This retrospective, real-world efficacy study included patients with untreated pMMR/MSS rectal adenocarcinoma aged 18 to 75 years, with clinical stages II-III and no prior systemic or local anticancer treatment. Patients received either LCRT (GTV 50Gy/25 fractions) or SCRT (GTV 25Gy/5 fractions), alongside 5-FU-based chemotherapy and PD-1 antibody therapy. Primary endpoints were PCR and clinical complete response (CCR) rates, while secondary endpoints included the incidence of acute adverse reactions and postoperative complications. The study aimed to provide further evidence for future treatment strategies by comparing the efficacy differences between these two radiotherapy regimens in combination with immunotherapy. Results: From January 2021 to December 2024, a total of 129 patients were enrolled. Among the 129 patients, 9 (2 received SCRT and 7 received LCRT) patients underwent "watch and wait" strategy due to imaging assessment of CCR. Of the 129 evaluable patients, 36 received SCRT and 93 received LCRT. The median age was 59 years (range: 22-75), with 44 females (34.1%). Stage III patients accounted for 119 (92.2%). Among high-risk patients, 86 (66.7%) had tumors located ≤5 cm from the anus, 81 (62.8%) were MRF (+) status and 62 (48.1%) were EMVI (+) status. The 120 patients who underwent total mesorectal excision surgery showed a PCR rate of 44.1% in the SCRT group compared to that of 40.7% in the LCRT group (p = 0.732). The CCR rate was 41.7% in the SCRT group, which was higher than that of 30.1% in the LCRT group (p = 0.212). No significant differences in acute toxicities were observed between the two radiotherapy modalities. The most common treatment-related adverse events were mainly grade 1-2 hematologic toxicity (37.2%), gastrointestinal toxicity (25.2%), and neurotoxicity (14.7%), with no severe treatment-related adverse events reported. Conclusions: SCRT combined with immunotherapy appeared to show more favorable PCR/CCR rates than LCRT combined with immunotherapy in patients with pMMR/MSS rectal adenocarcinoma, suggesting it as a promising treatment option. Further follow-up is required to assess long-term survival outcomes, and prospective randomized controlled studies are needed to validate these findings.