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Updated: May 28, 2026
Robot-assisted Total Mesorectal Excision and Lateral Pelvic Lymph Node Dissection for Locally Advanced Middle-low Rectal Cancer
Published on: February 12, 2022
Total Neoadjuvant Therapy, Organ Preservation and Beyond: A State-of-the-Art Systematic Review and Critical Appraisal
Nabil Ismaili1,2,3
1Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS), Casablanca 82403, Morocco.
Background:
Locally advanced rectal cancer (LARC) management has evolved, but surgery (total mesorectal excision, TME) remains the curative cornerstone. Total neoadjuvant therapy (TNT) and organ preservation (OP) have emerged as response-adaptive strategies. We conducted a state-of-the-art systematic review to critically appraise TNT efficacy, trade-offs, OP feasibility, and emerging biomarkers.
Methods:
Following PRISMA 2020 guidelines, we searched PubMed, MEDLINE, Scopus, and EMBASE (1990-March 2026) plus ASCO/ESMO abstracts (2020-2026). We included phase II/III randomised controlled trials and major prospective studies evaluating neoadjuvant strategies in non-metastatic LARC. Risk of bias was assessed using RoB 2. Given heterogeneity, a narrative synthesis was performed (PROSPERO: CRD420251252675).
Results:
From 2847 records, 45 publications (30 trials) were included. For high-risk LARC (cT4, cN2, EMVI+, MRF+, tumour deposits), TNT improves disease-free survival and reduces distant metastases versus standard chemoradiotherapy (RAPIDO, PRODIGE 23, STELLAR, TNTCRT). However, TNT increases locoregional recurrence risk with short-course radiotherapy (RAPIDO: 10% vs. 6%; Polish II: no sustained overall survival benefit). Organ preservation is achievable in expert centres (OPRA: 54% 5-year TME-free survival; OPERA; CAO/ARO/AIO-16), but surgery remains the durable standard for most patients. De-escalation (PROSPECT, CONVERT, FOWARC, OCUM) avoids radiotherapy in low-risk (mrMRF-) patients without compromising local control. Lateral pelvic lymph node involvement (LPLN+) remains a negative prognostic factor even after TNT. Immunotherapy added to TNT (UNION, STELLAR II, SPRING-01, PRECAM) increases pCR rates (40-60%) but remains investigational. ctDNA-guided adaptation (CINTS-R) is feasible but requires mature data.
Conclusions:
Surgery (TME) is the definitive curative treatment for LARC. TNT is a preferred intensification strategy for high-risk patients, but trade-offs between systemic and local control must be individualised. Organ preservation is safe only for selected patients in expert centres. Immunotherapy-TNT combinations and ctDNA guidance are promising but not yet standard. This review provides an evidence-based roadmap for integrating these advances without losing sight of surgery's central role.