European journal of cancer (Oxford, England : 1990)
September 11, 2026 · via Europe PMC
Oncological impact of adjuvant chemotherapy after rectal cancer excision in the era of FOLFIRINOX-based TNT: A pooled post-hoc analysis of GRECCAR4-PRODIGE23.
Denost Q, Rouanet P, Teruel E, +11 more, GRECCAR and PRODIGE Study Groups.
AI summary — for doctors, generated from the abstract only
Adjuvant chemotherapy was associated with better outcomes in ypN+ rectal cancer after standard chemoradiotherapy but showed no association after FOLFIRINOX-based total neoadjuvant therapy.
What was studied
A pooled post hoc analysis of 489 patients from the French GRECCAR4 and PRODIGE23 trials (ypN+ or ypN0/cN+), comparing those who did and did not receive adjuvant chemotherapy, with propensity score adjustment.
Key findings
- Median follow-up 70 months; overall 3-year DFS 77%
- Adjuvant chemotherapy was associated with improved DFS in ypN+ patients after CRT (specific statistic not fully captured in the abstract)
- No significant association with outcomes after TNT, regardless of nodal status
Clinical relevance
This raises the possibility of de-escalating adjuvant chemotherapy after FOLFIRINOX-based TNT. As a post hoc non-randomized comparison, it is hypothesis-generating.
Who should care
Limitations
Post hoc analysis with non-randomized adjuvant allocation and residual confounding; small subgroups (e.g., only 25 ypN+ without adjuvant chemotherapy).
After intensive total neoadjuvant therapy for rectal cancer, more chemotherapy after surgery may add little.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
The role of adjuvant chemotherapy (AC) after total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) remains controversial, mainly based on colon cancer protocols, with recent validation of the equivalence of the 3- and 6-month CT regimens. The aim of this study is to evaluate the oncological impact of AC in the era of TNT in patients with LARC.
Methods
We conducted a post hoc analysis of ypN+ and ypN0/cN+ subgroups from two French multicentre randomized trials GRECCAR 4(NCT01333709) and PRODIGE 23(NCT01804790). Patients received either long-course chemoradiotherapy (CRT) or TNT with FOLFIRINOX 4-6 cycles followed by CRT.In each subgroup, outcomes of patients who received AC (AC+) were compared with those who did not(AC-).The primary outcome was 3-year Disease-free survival(DFS).Secondary endpoints included 3-year overall survival(OS),distant metastasis and local recurrence free-survival(3y-DMFS and 3y-LRFS). Survivals were adjusted on propensity score.
Results
Among 489 patients were eligible, 152 AC- (25ypN+ and 127ypN0/cN+)vs 337 AC+ (119 ypN+ and 218 ypN0/cN+).Baseline tumor characteristics were similar. Median follow-up was 70 months. Overall 3y-DFS was 77% and was significantly improved in AC+ group for ypN+ after CRT (p < 0.001), but not after TNT. For ypN0/cN+, no statistically significant association was observed regarding the 3y-DFS whatever the neoadjuvant treatment,TNT (p = 0.33) or CRT (p = 0.45).Similarly, the AC+ group had a significantly better 3y-OS (p < 0.001), 3y-DMFS (p ≤ 0.001) and 3y-LRFS (p ≤ 0.001) for ypN+ after CRT, but not after TNT. For ypN0/cN+, there was no significant difference between the 2 groups regarding 3y-OS(p = 0.74), 3y-DMFS(p = 0.72) and 3y-LRFS(p = 0.71),whatever the neoadjuvant treatment.
Conclusions
Adjuvant chemotherapy was associated with significantly improved oncological outcomes in ypN+ patients after CRT, whereas no significant association was observed after TNT, irrespective of nodal status. These findings may support de-escalation of adjuvant therapy in the TNT era and inform a more individualised postoperative strategy.
DOI
10.1016/j.ejca.2026.117046
PMID
42743888
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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