Table 2.

Total neoadjuvant therapy.

Trials	Patients (n)	Treatment Methods	Results(INCT vs. CNCT)	Conclusion	Ref
CAO/ARO/ AIO-12	INCT = 156	INCT: chemotherapy/CRT/surgery	pCR: 17% vs. 25%	CNCT resulted in better compliance with CRT but worse compliance with chemotherapy compared with INCT.	[33,34]
			3 y-DFS: 73% vs. 73%, p = 0.82
	CNCT = 150		OS: 92% vs. 92%, p = 0.81
			CRT-related grade 3 or 4 toxicity: 37% vs. 27%
OPRA	INCT = 152		DFS: 78% vs. 77%, p = 0.90	CNCT resulted in a numerically higher WW rate compared to induction chemotherapy followed by CRT.	[36]
	CNCT = 155	CNCT: CRT/chemotherapy/surgery	DMFS: 81% vs. 83%, p = 0.86
			OP: 43% vs. 58%, p = 0.01
PRODIGE 23	INCT = 230		3 y-DFS: 69% vs. 76%, p = 0.034	Neoadjuvant mFOLFIRINOX plus CRT is safe and significantly increases ypCR rate, DFS and MFS.	[37,38]
			3 y-MFS: 71.7% vs. 78.8%, p < 0.02
	CNCT = 231		pCR: 11.7% vs. 27.5%, p < 0.001
			3 y-OS: 87.7% vs. 90.8%, p = 0.077
RAPIDO	standard arm = 441	standard arm: RT: 50 Gy (5 × 2 Gy/w) or 50.4 Gy (5 × 1.8 Gy/w)	3 y-DrTF: 30.4% vs. 23.7%, p = 0.019	The 3 y-DrTF rate was significantly reduced by 7%, and the pCR rate was increased from 14% to 28% in the short-course radiotherapy, followed by consolidation chemotherapy and TME.	[39]
	experimental arm = 460	capecitabine experimental arm: RT: 5 × 5 Gy CAPOX × 6 cycles or FOLFOX4 × 9 cycles	3 y-OS: 88.8% vs. 89.1%, p = 0.59
			R0 resection rate: 90% vs. 90%, p = 0.87
			pCR: 14% vs. 28%, p < 0.0001

INCT = induction chemotherapy; CNCT = consolidation chemotherapy; CRT = chemoradiotherapy; DMFS = distant metastasis-free survival; OP = organ preservation; DrTF = disease-related treatment failure; Gy = Gray; TME = total mesorectal excision; WW = watch and wait; y = year.