Table 1:
Major total neoadjuvant randomized controlled trials.
| Study | Stage | N | Arms | pCR (%) | DFS (%) | OS (%) |
|---|---|---|---|---|---|---|
| RAPIDO | cT4, or EMVI+, CN2, MRF+, or LPLN+ | 450 | Standard: 5FU-CRT→Surgery→ ±FOLFOX(12)/CAPOX(8) | 14.3 | *DRTF: 30 | 89 |
| 462 | Consolidation: SCRT→FOLFOX(9)/CAPOX(6)→Surgery | 28.42 | *DRTF: 24*DRTF: | 89 | ||
| PRODIGE-23 | cT3 or cT4 | 230 | Standard: 5FU-CRT→Surgery→mFOLFOX/capecitabine(3) | 12.1 | 62.5 | 76.1 |
| 231 | Induction: FOLFIRINOX(6)→ 5FU-CRT→Surgery→mFOLFOX/capecitabine(6) | 27.8 | 67.6 | 81.9 | ||
| POLISH II | Primary or locally recurrent cT4, or a palpable fixed cT3 | 254 | Standard: 5FU/OX-CRT→Surgery→± ChT | 12 | 43 | 49 |
| 261 | Consolidation: SCRT→FOLFOX(3)→Surgery→± ChT | 16 | 41 | 49 | ||
| STELLAR | Primary cT3–4 or N+ in mid to distal rectum | 293 | Standard: CAPE-CRT→Surgery→CAPOX(6) | 12.3 | 62 | 75 |
| 298 | Consolidation: SCRT→CAPOX(4)→Surgery→CAPOX(2) | 21.8 | 65 | 87 | ||
| CAO/ARO/AIO-12 | cT3 if < 6 cm from AV; > cT3b if 6–12 cm from AV; cT4, or LPLN+ | 156 | Consolidation: 5FU/OX-RT→FOLFOX(3)→Surgery | 25 | 73 | 92 |
| 150 | Induction: FOLFOX(3)→ 5FU/OX-CRT→Surgery | 17 | 73 | 92 | ||
| OPRA | AJCC stage III–IV | 155 | Consolidation: 5FU-CRT→ FOLFOX/CAPOX(4 mo)→Surgery | NR | 76 | NR |
| 152 | Induction: FOLFOX/CAPOX(4 mo)→5FU-CRT→Surgery | NR | 76 | NR |
[i] 5FU = fluorouracil, AJCC = American Joint Committee on Cancer, AV = anal verge, CAO/ARO/AIO-12 = Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy trial, CAPOX = capecitabine combined with oxaliplatin, CAPE = capecitabine, CRT = chemoradiotherapy, DFS = disease-free survival, DRTF = disease-related treatment failure, EMVI+ = extramural vascular invasion, FOLFIRINOX = leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride and oxaliplatin, FOLFOX = leucovorin calcium (folinic acid), fluorouracil and oxaliplatin, LPLN+ = lateral pelvic lymph node involvement, MRF+ = mesorectal fascia involvement, NR = not reported, OPRA = Organ Preservation of Rectal Adenocarcinoma study, OS = overall survival, OX = oxaliplatin, pCR = pathologic complete response, PRODIGE-23 = Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer, RAPIDO = Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation trial, SCRT = short-course radiotherapy, STELLAR = Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer
Table 2:
Disease characteristics of patients enrolled in major TNT RCTs.
| Trial | T2 | T3 | T4 | N0 | MRF+ | EMVI | LLN |
|---|---|---|---|---|---|---|---|
| RAPIDO | 3 | 66 | 31 | 9 | 61 | 30 | 15 |
| POLISH II | 3 | 34 | 64 | NS | NS | NS | NS |
| STELLAR | 3 | 84 | 14 | 15 | 56 | 48 | NS |
| Prodige-23 | 0 | 83 | 17 | 10 | 22 | NS | 10 |
| CAO/AIO/ARO-12 | 4 | 71 | 15 | 10 | 27 | NS | NS |
| OPRA | 10 | 77 | 13 | 29 | NS | NS | NS |
[i] PRODIGE-23 = Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer, RAPIDO = Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation trial, STELLAR = Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer, OPRA = Organ Preservation of Rectal Adenocarcinoma study, CAO/ARO/AIO-12 = Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy trial, EMVI = extramural vascular invasion, MRF = mesorectal fascia involvement, LLN = Lateral Lymph Node