Correlation between pathological response to neoadjuvant immunotherapy and long-term survival in locally advanced rectal cancer: A real-world study

BACKGROUND Conventional treatment for locally advanced rectal cancer (LARC) is associated with several limitations, and neoadjuvant immunotherapy has been proposed to address these current clinical dilemmas. However, the correlation between pathological response and long-term survival remains unclear. Most existing studies are derived from clinical trials, with a lack of real-world evidence. Therefore, this real-world study was conducted to analyze the correlation between the two indicators. AIM To investigate the correlation between pathological response to neoadjuvant immunotherapy and long-term survival in patients with LARC using real-world data. METHODS Clinical data of 130 LARC patients who received neoadjuvant immunotherapy combined with radical surgery in our hospital from March 2022 to March 2025 were retrospectively collected. All patients were administered neoadjuvant immunotherapy regimens based on anti-programmed cell death protein 1/programmed death-ligand 1 inhibitors, and laparoscopic or open radical resection of rectal cancer was performed 4-6 weeks after the end of treatment. Tumor regression grade (TRG) was used to evaluate the degree of pathological response, which was classified into pathological complete response (pCR; TRG grade 0), major pathological response (MPR; TRG grade 1), and non-MPR (TRG grades 2-3). The Kaplan-Meier method was adopted for survival analysis, and the log-rank test was used to compare disease-free survival and overall survival among patients with different pathological response grades. The Cox proportional hazards regression model was applied to identify the independent risk factors for long-term survival in these patients. RESULTS Among the 130 patients with LARC who received neoadjuvant immunotherapy followed by radical surgery, 30 patients achieved pCR, 30 achieved MPR, and 70 were classified as non-MPR. Significant differences were observed among the groups in maximum tumor diameter, preoperative imaging T stage, preoperative imaging N stage, and treatment regimen (all P < 0.05). Patients with better pathological response demonstrated more favorable survival outcomes than those without MPR. In addition, neoadjuvant immunotherapy exhibited an acceptable safety profile, and treatment-related adverse events were generally manageable. CONCLUSION Neoadjuvant immunotherapy yields a high pathological response rate in LARC patients, and the pathological response is closely correlated with long-term survival outcomes. Patients achieving pCR/MPR have superior disease-free survival and overall survival.