TNT Shows Similar Efficacy Across Regimens in Rectal Cancer

TOPLINE:

In a multicentre study of patients with locally advanced rectal cancer, substantial variation existed in the choice of total neoadjuvant therapy (TNT), but efficacy was comparable across different regimens and consistent with that reported in clinical trials.

METHODOLOGY:

• Researchers conducted an international, multicentre study in 21 countries and included 1585 patients (median age, 61 years; 37.1% women) with stage II/III rectal adenocarcinoma from September 2012 to December 2023.
• The primary objective focused on the type of TNT administered depending on the regimen, timing and type of chemotherapy, and type of radiotherapy. Secondary objectives encompassed safety and efficacy overall and on the basis of the type of TNT after propensity vector matching.
• Efficacy endpoints included pathologic complete response, complete response, local or distant progression at the time of treatment failure, event-free survival (EFS), and overall survival (OS).
• Overall, 17.7%, 33.4%, 12%, and 16.2% of patients were treated according to PRODIGE 23-like, RAPIDO-like, OPRA induction-like, and OPRA consolidation-like regimens, respectively.

TAKEAWAY:

• Chemotherapy was given as induction, consolidation, and sandwich for 34.5%, 51.0%, and 14.5% of patients, respectively; regimens were single agent (1.1%), doublet (78.8%), and triplet (20.1%). Radiotherapy was delivered as short-course radiotherapy in 37.2% and long-course chemoradiotherapy in 62.8% of cases.
• The pathologic complete response rate was 21.3%, and the complete response rate was 23.2%; local and distant progression at the time of treatment failure were 7% and 16.2%, respectively.
• Three-year EFS reached 68%, and 5-year OS was 79%.
• In the overall population, PRODIGE 23-like regimens showed better survival outcomes than RAPIDO-like regimens (EFS: hazard ratio [HR], 0.68; P = .03; OS: HR, 0.51; P = .04), OPRA induction-like regimens (EFS: HR, 0.66; P = .04; OS: HR, 0.35; P = .003), and OPRA consolidation-like regimens (EFS: HR, 0.64; P = .02; OS: HR, 0.50; P = .05).
• After the propensity vector matching analysis of 928 patients (58.5%), no significant differences in survival outcomes were observed between TNT regimens.

IN PRACTICE:

“This case series study illuminates the applicability of TNT to clinical practice,” the authors of the study wrote. “TNT decisions should be made based on the individual risk profile and following an accurate discussion about the positives and negatives of each option while considering patient preferences and expectations,” they added.

SOURCE:

This study was led by Alessandro Audisio, MD, Université libre de Bruxelles, Institut Jules Bordet-Hôpital Erasme, Brussels, Belgium. It was published online on July 10, 2025, in JAMA Oncology.

LIMITATIONS:

The retrospective design of the study introduced potential data collection errors and biases, which were only partially addressed through remote monitoring and data imputation. The relatively short follow-up period may have prevented the detection of differences in long-term outcomes between TNT regimens. Additionally, variations in treatment delivery, staging methods, and supportive care across institutions complicated direct comparisons. Despite involving multiple countries, the predominant European patient population limited the generalisability of the results.

DISCLOSURES:

This study was sponsored by the Institut Jules Bordet and endorsed by the Oncodistinct Network. Several authors reported receiving personal fees and grants and having other ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.