Total neoadjuvant therapy for locally advanced rectal cancer: barriers to implementation in real-world practice

Total neoadjuvant therapy (TNT) has demonstrated superior oncologic outcomes and improved organ preservation in randomized trials for locally advanced rectal cancer (LARC). This study aimed to assess the real-world implementation of TNT in clinical routine and identify barriers to its application. This retrospective, multicenter cohort study analyzed 111 patients with LARC treated between February 2021 and May 2024 across three certified colorectal cancer centers in Germany. Patients were stratified into TNT and non-TNT groups according to their neoadjuvant treatment modality. Primary endpoints included treatment adherence, disease-free survival (DFS), postoperative morbidity, and documented reasons for omitting TNT. Outcomes were compared with benchmark protocols from established TNT trials. Despite fulfilling guideline criteria, only 23 of 111 patients (20%) received TNT. Main barriers to TNT included advanced age, comorbidities, and patient refusal. The 1-year DFS rate was 96% in the TNT group and 94% in the non-TNT group. Severe low anterior resection syndrome (LARS) occurred in 9% of TNT patients compared to 22% in the non-TNT group. Postoperative complication rates were similar across both groups. While TNT was associated with favorable trends in disease control and functional outcomes, statistical significance was not reached. There is a notable discrepancy between clinical guideline recommendations and real-world TNT implementation in LARC. Addressing patient-specific barriers and adopting standardized, risk-adapted treatment decision frameworks may improve clinical integration of TNT, particularly in older and comorbid populations.