Landmark total neoadjuvant therapy randomized controlled trials
| Study (year) | Rectal cancers included | Treatment arms (no. of cycles) | N | Survival outcomes (%) | pCR (%) | Completed chemotherapy (%) | Received surgery (%) | R0 resection (%) | Follow-up (mo) |
|---|---|---|---|---|---|---|---|---|---|
| PRODIGE-23 (2020) (1) | cT3 or cT4 | Standard: 5FU-CRT→Surgery | 230 | DFS: 69* OS: 88 | 12.1* | 75 | 89 | 94 | 46.5 |
| Induction: FOLFIRINOX(6)→ 5FU-CRT→Surgery | 231 | DFS: 76* OS: 91 | 27.8* | 81 | 94 | 95 | |||
| RAPIDO (2020) (2) | cTa-b, or EMVI+, CN2, MRF+, or LPLN+ | Standard: 5FU-CRT→Surgery→ ±FOLFOX(12)/CAPOX(8) | 450 | DRTF: 30* OS: 89 | 14.3* | 66† | 89 | 90 | 54 |
| Consolidation: SCRT→FOLFOX(9)/ CAPOX(6)→Surgery Standard: 5FU/ OX-CRT→Surgery | 462 | DRTF: 24* OS: 89 | 28.4* | 85 | 92 | 90 | |||
| POLISH II (2019) (3) | Primary or locally recurrent cT4, or a palpable fixed cT3 | Standard: 5FU/OX-CRT→Surgery | 254 | DFS: 43 OS: 49 | 12 | NR | 92 | 71 | 84 |
| Consolidation: SCRT→FOLFOX(3)→Surgery | 261 | DFS: 41 OS: 49 | 16 | 99 | 93 | 77 | |||
| STELLAR (2022) (4) | Primary cT3–4 or N+ in mid to distal rectum | Standard: CAPE-CRT→Surgery→CAPOX(6) | 293 | DFS: 62 OS: 75* | 12.3* | 58 | 78.5 | 87.8 | 35 |
| Consolidation: SCRT→CAPOX(4) →Surgery→CAPOX(2) | 298 | DFS: 65 OS: 87* | 21.8* | 59 (98 neoadjuvant only) | 78.9 | 91.5 | |||
| CAO/ARO/ AIO-12 (2019) (6) | cT3 if < 6 cm from AV; > cT3b if 6–12 cm from AV; cT4, or LPLN+ | Consolidation: 5FU/OX-RT→FOLFOX(3)→Surgery | 156 | NR | 25 | 85 | 91 | 90 | NR |
| Induction: FOLFOX(3)→ 5FU/OX-CRT→Surgery | 150 | NR | 17 | 92 | 95 | 92 | |||
| OPRA (2020) (7) | AJCC stage III–IV | Consolidation: 5FU-CRT→ FOLFOX/CAPOX(4 mo)→Surgery | 155 | DFS: 77 DMFS: 83 | NR | NR | 42*‡ | NR | 25 |
| Induction: FOLFOX/ CAPOX(4 mo)→5FU-CRT→Surgery | 152 | DFS: 78 DMFS: 81 | NR | NR | 57*‡ | NR |
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; DMFS = distant metastasis-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.
↵* Indicates statistically significant outcome (p < 0.05).
↵† Percentage of patients offered adjuvant chemotherapy who completed the course.
↵‡ Inverse of organ preservation rate reported.