ReviewClinical and translational radiation oncology2026
Total neoadjuvant therapy for rectal cancer: where are we now, where do we go?
Review in Clinical and translational radiation oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Total neoadjuvant therapy (TNT) refers to the addition of an entire course of preoperative systemic therapy to short-course radiotherapy (SCRT; 5 × 5 Gy) or chemoradiation (CRT), either as induction chemotherapy before CRT or as consolidation therapy after SCRT/CRT, followed by total mesorectal excision (TME) surgery. Randomized trials have demonstrated improved pathological complete response rates and a significant improvement in disease-free survival with TNT compared to neoadjuvant CRT plus surgery with or without adjuvant chemotherapy. TNT is increasingly considered the preferred treatment strategy, especially for patients with MRI-defined high-risk rectal cancer. (such as cT4, cN2, Magnetic Resonance Circumferential Resection Margins Positive (mrCRM+), Extramural Vascular Invasion Positive (EMVI+), lateral lymph node involvement). Key questions remain, including the optimal RT regimen (SCRT vs. CRT), the sequence of treatment components (induction vs. consolidation therapy), the number of chemotherapy cycles, RT-dose escalation strategies, the need of adjuvant chemotherapy after TNT and surgery, and the role of immunotherapy in both mismatch repair-deficient and mismatch repair-proficient (dMMR/pMMR) disease. Due to the higher rates of clinical complete response achieved with TNT, organ-preserving ("watch-and-wait") strategies are increasingly favored and continue to be refined in ongoing clinical trials (e.g., ACO/ARO/AIO 18.1, JANUS, ENSEMBLE, TRESOR, and STELLAR II).
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