Adjuvant Chemo Shows No Clear Added Benefit After FOLFIRINOX-Based TNT in Pooled LARC Analysis

A pooled post-hoc analysis of two French randomized trials (GRECCAR 4; NCT01333709 and PRODIGE 23; NCT01804790) evaluated whether postoperative adjuvant chemotherapy (typically fluoropyrimidine/oxaliplatin-based) adds oncologic benefit after rectal cancer excision in locally advanced rectal cancer (LARC) patients treated with either standard long-course chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT) that included 4–6 cycles of (m)FOLFIRINOX followed by CRT. Across 489 eligible patients (AC- n=152 vs AC+ n=337; median follow-up 70 months), adjuvant chemotherapy was associated with significantly better 3-year DFS/OS/DMFS/LRFS only in ypN+ patients who had received CRT (all p≤0.001), while no statistically significant association was seen after TNT regardless of nodal status (e.g., ypN0/cN+ 3y-DFS: TNT p=0.33; CRT p=0.45). These results suggest the incremental value of postoperative chemotherapy may be smaller after FOLFIRINOX-based TNT, whereas ypN+ disease after CRT remains associated with better outcomes among patients who received adjuvant therapy; however, because postoperative chemotherapy was not randomized, the analysis cannot establish that adjuvant treatment is redundant or can safely be omitted after TNT.