Why Is There a Demand for Organ-Sparing Approaches in the Era of TNT and TME?

Abstract Total neoadjuvant therapy (TNT) has emerged as a transformative approach in the management of locally advanced rectal cancer, shifting radiation and chemotherapy to the preoperative setting to optimize local and distant disease control. Landmark trials have demonstrated improved compliance, tumor downstaging, and disease-free survival with TNT, increasing options for nonoperative strategies such as watch-and-wait. This paradigm allows patients who achieve a clinical complete response (cCR) to avoid surgery and its associated morbidity, including ostomy formation and low anterior resection syndrome (LARS). The Organ Preservation in Patients with Rectal Adenocarcinoma (OPRA) trial and other prospective studies have validated the oncologic safety of watch-and-wait, showing comparable disease-free and overall survival to traditional approaches, with salvage surgery effective in cases of regrowth. However, not all patients are ideal candidates for TNT and watch-and-wait protocols. Tumor location, anatomy, comorbidities, and patient preferences influence treatment selection. For mid-to-upper rectal tumors, TNT may be over-treatment, as suggested in the Preoperative Treatment of Locally Advanced Rectal Cancer (PROSPECT) Trial, which supports selective use of chemoradiation. This is an important option for patients wishing to preserve fertility. Additionally, predicting cCR and regrowth remain challenging, and intensive surveillance is required. This article reviews the evolution of TNT and watch-and-wait strategies, highlighting key trials such as OPRA, the Rectal Cancer and Preoperative Induction Therapy followed by Dedicated Operation (RAPIDO) Trial, the Partenariat de Recherche en Oncologie Digestive 23 (PRODIGE 23) Trial, the Organ Preservation after TNT for Locally Advanced Rectal Cancer (CAO/ARO/AIO-16) Trial, and PROSPECT. We examine the oncologic safety, organ preservation rates, and quality-of-life implications of nonoperative management, including the risks of LARS and ostomy formation. With multiple validated strategies, surgeons must balance oncologic outcomes with quality of life for each individual patient. Ongoing trials continue to refine these approaches, aiming to optimize tumor downstaging, integrate immunotherapy, and expand organ-preserving options.