Table 1

Landmark total neoadjuvant therapy randomized controlled trials

Study (year)Rectal cancers includedTreatment arms (no. of cycles)NSurvival outcomes (%)pCR (%)Completed chemotherapy (%)Received surgery (%)R0 resection (%)Follow-up (mo)
PRODIGE-23 (2020) (1)cT3 or cT4Standard: 5FU-CRT→Surgery230DFS: 69*
OS: 88
Induction: FOLFIRINOX(6)→ 5FU-CRT→Surgery231DFS: 76*
OS: 91
RAPIDO (2020) (2)cTa-b, or EMVI+, CN2, MRF+, or LPLN+Standard: 5FU-CRT→Surgery→ ±FOLFOX(12)/CAPOX(8)450DRTF: 30*
OS: 89
Consolidation: SCRT→FOLFOX(9)/ CAPOX(6)→Surgery Standard: 5FU/ OX-CRT→Surgery462DRTF: 24*
OS: 89
POLISH II (2019) (3)Primary or locally recurrent cT4, or a palpable fixed cT3Standard: 5FU/OX-CRT→Surgery254DFS: 43
OS: 49
Consolidation: SCRT→FOLFOX(3)→Surgery261DFS: 41
OS: 49
STELLAR (2022) (4)Primary cT3–4 or N+ in mid to distal rectumStandard: CAPE-CRT→Surgery→CAPOX(6)293DFS: 62
OS: 75*
Consolidation: SCRT→CAPOX(4) →Surgery→CAPOX(2)298DFS: 65
OS: 87*
21.8*59 (98 neoadjuvant only)78.991.5
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)→Surgery156NR25859190NR
Induction: FOLFOX(3)→ 5FU/OX-CRT→Surgery150NR17929592
OPRA (2020) (7)AJCC stage III–IVConsolidation: 5FU-CRT→ FOLFOX/CAPOX(4 mo)→Surgery155DFS: 77
DMFS: 83
Induction: FOLFOX/ CAPOX(4 mo)→5FU-CRT→Surgery152DFS: 78
DMFS: 81
  • 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.