Top Line: Should total neoadjuvant therapy be the standard approach for high risk rectal cancer?
The Study: The TNT approach is gaining momentum in the management of locally advanced rectal cancer. Phase 3 data has been limited, but we are now seeing the results of several randomized TNT trials including the recent RAPIDO trial. Here is PRODIGE 23, which was a randomized phase 3 French trial where 461 patients with cT3 or cT4 rectal adenocarcinoma (90% were also LN+) were randomized to standard therapy or total neoadjuvant therapy...kinda. PRODIGE 23 didn’t do “pure” TNT. Instead, what we’ll call the “modified” TNT group received 3 of their 6 months of chemo before chemo-RT and then the remaining 3 months after surgery. In addition, the initial 3 months was an intensified triplet FOLFIRINOX regimen. Patients in both groups received neoadjuvant chemoRT consisting of 50 Gy in 25 fractions with capecitabine. After TME, everyone received either mFOLFOX6 or capecitabine (3 months for the mTNT group and 6 months for the standard group). At 3-years, mTNT significantly increased disease free survival (69→ 76%). mTNT reduced the rate of distant metastasis (25→ 17%) while maintaining a similar rate of locoregional failure (4% vs 6%). The proportion of patients who received planned chemoradiation was lower in the TNT arm (95% vs 99%), however there was no difference in the proportion of patients who proceeded to surgery. The pCR rate was also significantly higher with TNT (12→ 28%). There was no difference in 3-year overall survival.
TBL: Neoadjuvant FOLFIRINOX before standard chemoradiation for locally advanced rectal cancer significantly improves 3-year DFS while increasing the pCR rate, maintaining locoregional control, and decreasing distant failure. | Conroy, Lancet Oncol 2021