Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma

Table 1 Analysis of surgical data of 10966 patients with primary hepatocellular carcinoma

Stages and criteria	n (%)	Overall survival					Tumor recurrence
		Median time (mo)	1-yr survival rate (%)	3-yr survival rate (%)	5-yr survival rate (%)	10-yr survival rate (%)	Median time (mo)	1-yr recurrence rate (%)	2-yr recurrence rate (%)	3-yr recurrence rate (%)	5-yr recurrence rate (%)
First round of hepatectomy for HCC	2592	79.4	87.2	71.0	59.1	40.4	36.1	31.8	43.5	9.9	60.7
Stages Ia-IIIa	2549	82.3	88.1	71.9	60.0	41.0	37.0	31.0	42.9	49.3	60.3
Ia	1175	-	96.5	87.5	77.2	55.9	67.2	15.0	27.7	34.1	45.9
Ib	635	79.4	88.2	73.5	62.5	37.0	34.1	32.4	43.7	51.8	63.4
IIa	205	43.5	89.8	56.0	40.8	27.2	15.7	45.7	59.8	65.5	84.3
IIb	119	38.0	83.6	55.3	37.4	23.2	10.0	55.9	67.7	74.0	80.1
IIIa	415	21.9	65.1	38.2	23.8	16.0	7.9	59.9	69.8	73.8	80.2
IIIb	43	8.7	34.1	15.8	0	0	3.9	77.1	77.1	82.8	-

Overall survival and tumor recurrence of patients with different stages of hepatocellular carcinoma after undergoing hepatectomy[8]. Stages and criteria; overall survival; tumor recurrence; n; median time (months); 1-yr survival rate (%); 3-yr survival rate (%); 5-yr survival rate (%); 10-yr survival rate (%); median time (months); 1-yr recurrence rate (%); 2-yr recurrence rate (%); 3-yr recurrence rate (%); 5-yr recurrence rate (%); first round of hepatectomy for hepatocellular carcinoma; stages Ia-IIIa. HCC: Hepatocellular carcinoma.

Table 2 Evidence of studies on the neoadjuvant therapy

Treatment regimen	Study design	Number of patients	Treatment cycle	Study outcomes
Apatinib + camrelizumab[45]	Phase II	20	6 wk	MPR: 29.4%. PCR: 5.9%
Cabozantinib + nivolumab[46]	Phase I	15	8 wk	12 patients received R0 resection, and MPR or PCR was found in 5 patients (41.7%)
Toripalimab ± lenvatinib	Phase Ib/II	16	21-28 d	3 patients (20%) with MPR
Ipilimumab + nivolumab[47]	Phase Ib	7	6 wk	ORR of 20%; of the 5 patients with pathologically assessable tumors, 3 (60%) were found with pathological remission
Ipilimumab ± nivolumab[48]	Phase II	30	6 wk	Pathological remission rate: 30% (8/27), MPR: 11% (3/27), PCR: 19% (5/27)

MPR: Major pathological response; PCR: Pathological complete response; ORR: Objective remission rate.

Table 3 Evidence for systemic therapy plus local therapy in conversion therapy

Ref.	Treatment regimen	Number of patients, n (%)	Study results
Zhang et al[37], 2020	TKI: Lenvatinib. PD-1 antibody: Pembrolizumab/Sintilimab/Toripalimab	33	Success rate of conversion (imaging): 42.4%. Actual surgery rate following conversion: 30.3%
Li et al[40], 2017	TACE + sorafenib	142	Second-stage resection rate following stage reduction: 14.8%
He et al[39], 2019	HAIC + sorafenib	125	Surgical resection rate following conversion: 12.8%
He et al[41], 2018	HAIC + sorafenib	35	Surgical resection rate following conversion: 14.3%
Zhang et al[42], 2021	HAIC + TKI + PD-1 antibody (1, 7, and 17 patients used sorafenib, apatinib, and lenvatinib, respectively)	25	Surgical resection rate following conversion: 56.0%, 7 patients (28.0%) achieved pathologically complete remission
He et al[38], 2021	Lenvatinib + toripalimab + HAIC	71	Surgical resection rate following conversion: 12.7%

Grade of evidence in the guideline of Chinese Society of Clinical Oncology diagnosis and treatment. Feature of evidence; grade; level; sources; Chinese Society of Clinical Oncology degree of expert consensus; 1A: High, rigorous meta-analysis, large-scale randomized clinical study, unified consensus (supportive opinion: ≥ 80%); 1B: High, rigorous meta-analysis, large-scale randomized clinical study, generally unified consensus, with slight controversy (supportive opinion: 60%-80%); 2A: Slightly low, fair-quality meta-analysis, generally unified consensus, with slight controversy (supportive opinion: 60%-80%) or small-scale randomized clinical study, well-designed large-scale retrospective study, case-control study, unified consensus (supportive opinion: ≥ 80%); 2B: Slightly low, fair-quality meta-analysis, small-scale randomized clinical study, well-designed large-scale air-quality meta-analysis, generally unified consensus, with slight controversy (supportive opinion: 60%-80%) or small-scale randomized clinical study, well-designed large-scale retrospective study, case-control retrospective study, case-control study; generally unified consensus, with slight controversy (supportive opinion: 60%-80%); 3: Low, non-controlled single-arm clinical study, case report, expert opinion, no consensus, with low substantial controversy (supportive opinion: < 60%). TKI: Tyrosine kinase inhibitor; PD-1: Programmed cell death protein-1; TACE: Transarterial chemoembolization; HAIC: Hepatic arterial infusion chemotherapy.