Home›Oncology› Total neoadjuvant therapy improves disease-free survival and doubles pCR in rectal cancer
Total neoadjuvant therapy improves disease-free survival and doubles pCR in rectal cancerTotal Neoadjuvant Therapy Shows Improved Survival for Rectal Cancer
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical OncologyPublished August 2, 2026Study authors: Choi Sang-Ji, Chae GibongPubMed ↗DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Consider TNT for improved DFS and pCR, but weigh the non-significant LR increase and lack of OS benefit.
This meta-analysis pooled data from 2104 adults with MRI-confirmed locally advanced rectal cancer (cT3-4 and/or cN+, M0) to compare total neoadjuvant therapy (TNT) with standard neoadjuvant chemoradiotherapy (nCRT). The primary outcome was disease-free survival (DFS), with secondary outcomes including overall survival (OS), pathological complete response (pCR), locoregional recurrence (LR), and distant metastasis (DM). Follow-up ranged from 67 to 87 months.
TNT was associated with a statistically significant improvement in DFS (HR 0.85, 95% CI 0.74-0.98, P = 0.025). The pCR rate nearly doubled with TNT (OR 1.99, 95% CI 1.45-2.73, P < 0.001). However, OS did not differ significantly between groups (HR 0.89, 95% CI 0.76-1.05), and DM was not significantly reduced (OR 0.81, 95% CI 0.64-1.03).
Locoregional recurrence was not significantly different in the primary analysis (OR 1.24, 95% CI 0.95-1.62, P = 0.111), but a harmonized sensitivity analysis showed a non-significant numerical increase (OR 1.38, 95% CI 0.98-1.95, P = 0.062). The authors note this as a hypothesis-generating signal for potential increased pelvic recurrences with TNT.
The authors did not report adverse events, tolerability, or funding details. The main limitation is the potential for increased true pelvic recurrences with TNT, which tempers the long-term benefit relative to short-term gains. Clinically, TNT offers a meaningful improvement in DFS and pCR, but the lack of OS benefit and the concerning LR signal suggest that patient selection and surveillance remain important.
Researchers analyzed data from over 2,100 adults with MRI-confirmed locally advanced rectal cancer. They compared a method called total neoadjuvant therapy (TNT) against the standard treatment of chemoradiotherapy alone. The study looked at how these treatments affected survival rates and whether the tumors disappeared completely before surgery.
The results showed that patients receiving TNT had better disease-free survival and nearly doubled their chances of achieving a pathological complete response. This means the cancer was less likely to return in the short term. However, the study did not find a significant difference in overall survival or a reduction in distant metastasis when comparing the two treatments.
Because the results on long-term outcomes are mixed, patients and doctors should look closely at these findings. While TNT shows promise for clearing tumors before surgery, it did not show a clear advantage in preventing cancer from spreading to other parts of the body. Talk with your medical team to see how these options fit into a specific treatment plan.
What this means for you:
TNT may improve disease-free survival and response rates but does not currently show better overall survival.
Common questions
What is the difference between TNT and standard treatment?
Standard treatment involves chemoradiotherapy. Total neoadjuvant therapy (TNT) is a more intensive approach used before surgery. In this study of 2,104 adults, TNT was found to nearly double the rate of pathological complete response compared to the standard method.
Does TNT help patients live longer?
The study did not find a significant difference in overall survival between those who received TNT and those who received standard chemoradiotherapy. While it improved disease-free survival, it did not show a clear benefit for total life expectancy.
Does this treatment stop cancer from spreading?
The study found that TNT did not significantly reduce the risk of distant metastasis compared to standard care. Additionally, there was no significant difference in locoregional recurrence between the two groups during the primary analysis.
BACKGROUND: Total neoadjuvant therapy (TNT) is increasingly used for locally advanced rectal cancer (LARC), but most evidence is based on short- or intermediate-term follow-up. We evaluated whether TNT improves long-term disease-free survival (DFS), overall survival (OS), pathological complete response (pCR), locoregional recurrence (LR), and distant metastasis (DM) compared with standard neoadjuvant chemoradiotherapy (nCRT).
PATIENTS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to March 2026 (PROSPERO CRD420261350004). Phase II/III randomized trials comparing TNT with nCRT in adults with MRI-confirmed LARC (cT3-4 and/or cN+, M0) and a minimum median follow-up of 5 years were included. Outcomes were pooled using DerSimonian-Laird random-effects models.
RESULTS: Five trials including 2104 patients were analyzed (1063 TNT, 1041 nCRT; median follow-up 67-87 months). TNT improved DFS (HR 0.85, 95% CI 0.74-0.98; P = 0.025; I = 0%) and pCR (OR 1.99, 95% CI 1.45-2.73; P < 0.001; I = 30.6%), but did not improve OS (HR 0.89, 95% CI 0.76-1.05) or significantly reduce DM (OR 0.81, 95% CI 0.64-1.03). LR was not significantly different in the primary analysis (OR 1.24, 95% CI 0.95-1.62; P = 0.111). In a harmonized sensitivity analysis restricted to true pelvic recurrences after complete resection, LR showed a non-significant numerical increase with TNT (OR 1.38, 95% CI 0.98-1.95; P = 0.062).
CONCLUSIONS: TNT nearly doubled pCR and modestly improved long-term DFS, but did not improve OS or significantly reduce DM. Although not statistically significant, a possible increase in true LR could not be excluded; this hypothesis-generating signal, together with the absence of an OS benefit, suggests that the long-term benefit of TNT may be more limited than short-term outcomes imply.
