Clinical Outcomes of Different Preoperative Treatment Approaches in Locally Advanced Rectal Cancer: Real-World Experience

Background: To date, standard treatment for locally advanced rectal cancer (LARC) is total neoadjuvant therapy (TNT). Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the other option. This study aimed to compare the outcomes of various preoperative treatment strategies in real world setting. Methods: A retrospective and prospective analysis of stage II-III LARC patients receiving nCRT between January 2018 and October 2023 was conducted. Preoperative strategies were categorized into 3 groups: conventional nCRT, TNT, and nCRT with perioperative chemotherapy(nCRT-POC). We analyzed pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Results: Among 339 patients who completed preoperative treatment, 46%, 45%, and 9% of patients were treated with conventional nCRT, TNT, and nCRT-POC, respectively. During the treatment, 24 patients experienced tumor progressions, while 27 achieved a clinical complete response and underwent the watch-and-wait approach. Pathological data were available for 274 patients. The pCR rates were 11%, 24%, and 31% for the conventional nCRT, TNT, and nCRT-POC groups, respectively. Factors associated with pCR included poorly differentiated histology (OR: 7.1; P = 0.018), and TNT or nCRT-POC strategy (OR: 2.37; P = 0.03). Patients achieving pCR had significantly improved 3-year EFS (HR: 0.17; P <0.001) and 3-year OS (HR 0.10; P =0.002). No differences were observed in EFS and OS among all treatment strategies. TNT and nCRT-POC had significantly higher chemotherapy compliance than conventional nCRT (87%, 68%, and 57%, respectively, P<0.001). Conclusions: Our study indicated that the TNT and nCRT-POC strategy yielded higher pCR rates and chemotherapy compliance than conventional nCRT. We confirmed that patients attaining pCR were associated with improved 3-year EFS and OS.