Quentin Denost, Philippe Rouanet, Eva Teruel, Christophe Borg, Bernard Lelong, Pierre-Luc Etienne, Philippe Maingon, Emmanuel Rio, Jean-Jacques Tuech, Barbara Noiret, Stéphanie Nougaret, Veronica Pezzela, Sophie Gourgou, Thierry Conroy, GRECCAR and PRODIGE Study Groups
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.
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.