PRODIGE-23 Trial Treatment Arms
The PRODIGE-23 trial compared two treatment arms: (1) Standard arm received capecitabine-based chemoradiotherapy (CAPECRT) followed by surgery and then adjuvant chemotherapy (mFOLFOX6 or capecitabine for 12 cycles total), versus (2) Total neoadjuvant therapy (TNT) arm received 6 cycles of FOLFIRINOX followed by CAPECRT, then surgery, and then adjuvant chemotherapy (mFOLFOX6 or capecitabine for 6 cycles). 1
Treatment Arm Details
Standard-of-Care Arm (n=230)
- Preoperative: CAPECRT (capecitabine 800 mg/m² twice daily for 5 days/week concurrent with 50 Gy radiation over 5 weeks)
- Surgery: Total mesorectal excision
- Adjuvant: 12 cycles of either mFOLFOX6 or capecitabine 1, 2
Total Neoadjuvant Therapy Arm (n=231)
- Neoadjuvant chemotherapy: 6 cycles of FOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², leucovorin 400 mg/m², fluorouracil 2400 mg/m² IV every 14 days)
- Preoperative: CAPECRT (same regimen as standard arm)
- Surgery: Total mesorectal excision
- Adjuvant: 6 cycles of either mFOLFOX6 or capecitabine 1, 2
Key Distinction
The critical difference is that the TNT arm frontloaded intensive chemotherapy with FOLFIRINOX before chemoradiotherapy, while maintaining the same total treatment duration but shifting chemotherapy intensity to the neoadjuvant period. This resulted in patients in the TNT arm receiving 6 cycles of chemotherapy before surgery and 6 cycles after, compared to the standard arm which received all 12 cycles postoperatively 2.
Patient Population
The trial enrolled patients with locally advanced rectal adenocarcinoma (cT3/T4 M0) located below the peritoneal reflection on MRI, aged 18-75 years with WHO performance status 0-1. The majority had cT3a-b disease (45%), with 37% having tumors ≤5 cm from the anal verge 1, 2.
Long-Term Outcomes
With 82.2 months median follow-up, the TNT arm demonstrated superior outcomes: 7-year disease-free survival of 67.6% versus 62.5%, 7-year metastasis-free survival of 79.2% versus 72.3%, and 7-year overall survival of 81.9% versus 76.1% 3. The TNT approach achieved these improvements while reducing neurotoxicity during adjuvant therapy compared to standard treatment 2.