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Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Alessandro Audisio1,2, Chiara Gallio1, Vaneja Velenik3
1Université libre de Bruxelles, Hôpital Universitaire de Bruxelles, Institut Jules Bordet-Hôpital Erasme, Brussels, Belgium.
JAMA Oncology
|July 10, 2025
Summary
Total neoadjuvant therapy (TNT) for rectal cancer shows varied regimens in practice but aligns with trial efficacy. This study suggests TNT is effective in a clinical setting, regardless of the specific treatment plan used.
Area of Science:
- Oncology
- Clinical Research
- Gastrointestinal Oncology
Background:
- Rectal cancer treatment has evolved with the introduction of total neoadjuvant therapy (TNT).
- TNT involves delivering chemotherapy and radiotherapy before surgery or a watch-and-wait approach.
- Assessing TNT's real-world application and outcomes is crucial for optimizing patient care.
Purpose of the Study:
- To evaluate the utilization and clinical outcomes of total neoadjuvant therapy (TNT) in routine practice for rectal cancer.
- To compare the efficacy and safety of different TNT regimens in a large, international cohort.
Main Methods:
- An international, multicenter study included 1585 patients with stage II/III rectal adenocarcinoma treated with TNT.
- Patients received various TNT regimens, including PRODIGE 23-like, RAPIDO-like, and OPRA-like protocols.
- Outcomes assessed included treatment adherence, safety, pathological response, and survival (event-free and overall survival).
Main Results:
- Significant variation in TNT regimen choice was observed across 61 centers in 21 countries.
- Pathological or clinical complete response rates reached 23.2%, with 3-year event-free survival at 68% and 5-year overall survival at 79%.
- While PRODIGE 23-like regimens showed trends toward better survival in the overall population, no significant differences were found between regimens in the matched cohort.
Conclusions:
- Total neoadjuvant therapy (TNT) is utilized with considerable regimen diversity in clinical practice.
- The study findings support the overall efficacy of TNT for rectal cancer, consistent with clinical trial results.
- Real-world data suggest TNT is a viable and effective treatment strategy, irrespective of the specific regimen employed.
