Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Comparative Study of PRODIGE 23 versus RAPIDO Protocols

Background: Total neoadjuvant treatment (TNT) has significantly transformed the management of locally advanced rectal cancer (LARC). The PRODIGE 23 and RAPIDO trials introduced new strategies in TNT, demonstrating improved complete pathological response (pCR) rates and relapse-free survival. Objective: To compare clinical outcomes, toxicities, and response rates in patients treated with the PRODIGE 23 and RAPIDO TNT protocols. Methods: A retrospective, analytical study was conducted including 48 patients with LARC treated between January 2021 and December 2023 at CHU Hassan II of Fez. Patients were treated according to either the PRODIGE 23 or RAPIDO protocol. Clinical characteristics, treatment response, toxicities, and survival outcomes were compared. Results: The median age was 55.3 years, with 56.3% male patients. Most tumors were located in the mid-rectum, and all patients had adenocarcinoma. TNT was administered per PRODIGE 23 in 56.3% and RAPIDO in 43.8%. T4 tumors were more frequent in the PRODIGE 23 group (66.6% vs. 47.6%), although this difference was not statistically significant (p = 0.14). Nodal involvement was present in nearly all cases. The overall rate of grade ≥3 toxicities was 12.5%. The most common severe adverse events were neutropenia (14.6%), asthenia (8.3%), and anemia (6.3%). Pathological complete response was significantly higher with PRODIGE 23 (22.2%, p = 0.028). Median relapse-free, metastasis-free, and overall survival were 14.52, 14.98, and 21.83 months, respectively, with improved outcomes in the PRODIGE 23 group. Conclusion: PRODIGE 23 appears to offer superior pathological and survival outcomes compared to RAPIDO. Future prospective studies should aim to personalize TNT strategies and identify patients who would benefit most from treatment intensification or de-escalation.