Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?

Table 3 Comparison transarterial chemoembolization + radiofrequency ablation to other curative therapies

Ref.	Treatment type, n (%)	Clinical scenario	Response rate mRECIST	Outcome
Saviano et al[49], 2017	TACE + RFA (n = 25) vs HR (n = 29)	HCC 3.0-8.8 cm, solitary HCC 3-5 cm	N/A	OS (1, 3 yr): 89.4%, 48.2% vs 91.8%, 79.3% (P = 0.117). TR (1, 3 yr): 42.4%, 76.0% vs 29.5%, 45.0% (P = 0.034); LTP (3 yr): 58.1% vs 21.8% (P = 0.005). TR: 75.1% vs 35.4% (P = 0.016); LTP: 55.7% vs 16.0% P = 0.013)
Pan et al[50], 2017	TACE + RFA (n = 154) vs HR (n = 176)	Within Up-To Seven criteria	N/A	Median OS: 56 mo vs 58 mo (NS). OS (1, 3, 5 yr): 96.1%, 76.7%, 41.3% vs 96.1%, 86.4%, 46.2% (P = 0.138). Median OS (beyond Milan): 52 mo vs 45 mo (P = 0.023)
Liu et al[51], 2016	TACE + RFA (n = 100) vs HR (n = 100)	Within Milan	N/A	OS (1, 3, 5 yr): 96%, 67.2%, 45.7% vs 97%, 83.7%, 61.9% (P = 0.007). RFS (1, 3, 5 yr): 83%, 44.9%, 35.5% vs 94%, 68.2%, 48.4% (P = 0.026). Complications rate: 11% vs 23%, P = 0.024)
Lin et al[52], 2020	TACE (n = 231) vs TACE + RFA (n = 57) vs HR (n = 140)	BCLC-B	N/A	OS (1, 3, 5 yr): 69.5%, 37.0%, 15.2% vs 86.0%, 57.9%, 38.2% vs 89.2%, 69.4%, 61.2%. OS higher HR vs TACE + RFA (P = 0.009), HR vs TACE (P < 0.001) and TACE + RFA vs TACE (P = 0.004)
Wei et al[63], 2020	TACE + RFA (n = 107) vs HR (n = 79)	Recurrent HCC < 5 cm after HR	N/A	DFS (1, 3, 5 yr): 58.2%, 35.2%, 29.6% vs 64.8%, 41.6%, 38.3% (P = 0.258). OS (1, 3, 5 yr): 84.6%, 66.9%, 49.1% vs 84.8%, 60.2%, 51.9% (P = 0.871). Lower major complication rates (P = 0.009) and shorter hospital stay (P < 0.001) for TACE + RFA
Sheta et al[64], 2016	TACE (n = 20) vs TACE + RFA (n = 20) vs TACE + MWA (n = 10)	Non resectable single lesion HCC > 4 cm	50% vs 70% vs 80% (CR at 6 mo)	LTR (1, 3, 6 mo): 30% vs 5% vs 0% (P = 0.027); 14.3% vs 15.8% vs 10% (NS); 16.7% vs 12.5% vs 11.1% (NS). Complications rate: 40% vs 10% vs 10%
Yuan et al[65], 2019	TACE + RFA (n = 41) vs TACE + MWA (n = 34)	HCC > 3 cm. HCC 3-5 cm. HCC > 5 cm	68.3 vs 85.3% (NS). 73.5 vs 88.5% (NS). 42.9 vs 75% (P = 0.041)	DFS (1, 2, 3 yr): 53%, 29%, 12% vs 58%, 38%, 29% (P = 0.07). OS (1, 2, 3 yr): 68%, 36%, 14% vs 79%, 53%, 38% (P = 0.393)
Thornton et al[120], 2017	TAE/TACE + RFA (n = 15) vs TAE/TACE + MWA (n = 20)	BCLC 0 and A	80% vs 95% (NS)	LTR: 30% vs 0%
Vasnani et al[67], 2016	TACE + RFA (n = 11) vs TACE + MWA (n = 31)	HCC within Milan	91% vs 67% (CR) 45% vs 35% (rates of complete tumor coagulation on pathology)

mRECIST: Modified RECIST; n: Number of patients; BCLC: Barcelona Clinic Liver Cancer; TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation; MWA: Microwave ablation; HR: Hepatic resection; OS: Overall survival; PFS: Progression free survival; TTP: Time to progression; LTP: Local tumor progression; DFS: Disease free survival; TR: Tumor recurrence; CR: Complete response; NS: Not significative; N/A: Not applicable.