Pre-transplant downstaging strategies for hepatocellular carcinoma with portal vein tumor thrombus: Current therapies and future challenges

Table 1 Comparative classification of portal vein tumor thrombus and clinical implications

System	Grade/type	Anatomical extent	Typical characteristics	Downstaging feasibility
LCSGJ	Vp0	No portal vein invasion	Normal portal flow	Not applicable
	Vp1	Thrombus distal to second-order branches	Peripheral PVTT; limited hepatic impact	High: TACE, TARE, PBT often effective
	Vp2	Thrombus in second-order (segmental) branches	Segmental invasion; localized disease	Moderate to high
	Vp3	Thrombus in first-order (right/Left) portal vein	Major branch occlusion; moderate liver function compromise	Moderate: Requires combination approaches
	Vp4	Thrombus in main trunk or contralateral portal vein	Central occlusion; severe portal hypertension	Low: Systemic + radiation or experimental
Cheng	Type I	Segmental branches of the portal vein	Equivalent to Vp1-Vp2; good prognosis if treated early	High
	Type II	Right or left portal vein	Similar to Vp3; higher recurrence risk post resection	Moderate
	Type III	Main portal vein trunk	Equivalent to Vp4; marked hemodynamic impairment	Low
	Type IV	Extending into superior mesenteric vein	Extensive systemic vascular involvement	Very low: Limited to palliative/systemic care

LCSGJ: The Liver Cancer Study Group of Japan; TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; PVTT: Portal vein tumor thrombus; PBT: Proton beam therapy.

Table 2 Transarterial chemoembolization-based combination therapies for hepatocellular carcinoma with portal vein tumor thrombus

Ref.	Population	Treatment arms	ORR (%)	Median OS (months)	Median PFS (months)	Key findings
Yuan et al[5]	743 HCC with PVTT	TACE + HAIC + TKIs + PD-1 vs TACE	53.7 vs 7.8	Not reached vs 10.4	14.8 vs 2.3	Best surgical conversion and pCR outcomes
You et al[38]	265 HCC with PVTT	IT + TACE vs IT	–	19.0 vs 13.0	12.0 vs 7.3	TACE enhances immune-targeted response
Lu et al[39]	227 Vp2–Vp3 PVTT	TACE + PEI + Lenvatinib vs TACE + Lenvatinib	50.5 vs 25.8	17.1 vs 13.9	8.1 vs 6.5	PEI boosts PVTT regression
Lu et al[40]	105 Vp4 PVTT	125I stent + TACE vs Sorafenib + TACE	–	9.9 vs 6.3	6.6 vs 4.2	125I stent prolongs survival and patency
Zou et al[41]	165 HCC with PVTT	TACE + Lenvatinib + PD-1 vs TACE + Sorafenib + PD-1	41.3 vs 30.6	21.7 vs 15.6	6.3 vs 3.2	Lenvatinib triple better than Sorafenib triple
Lin et al[42]	95 PVTT + APFs	HAIC + Lenvatinib + PD-1 vs TACE + Lenvatinib + PD-1	52.9 vs 27.9	25.0 vs 19.3	21.7 vs 8.7	HAIC favored in APF setting
Zhao et al[43]	58 PVTT + APFs	TACE + 125I vs TACE + Sorafenib	–	12.8 vs 8.0	–	125I improves APF control and OS
Yang et al[44]	116 PVTT	TACE + Lenvatinib vs TACE + Sorafenib	66.8 vs 33.3	18.97 vs 10.77	10.6 vs 5.4	TACE-L significantly outperforms TACE-S in ORR, OS, and PFS

PFS: Progression-free survival; HCC: Hepatocellular carcinoma; TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; PVTT: Portal vein tumor thrombus; ORR: Objective response rate; OS: Overall survival; HAIC: Hepatic arterial infusion chemotherapy; APF: Atypical portal flow; PEI: Percutaneous ethanol injection; IT: Immunotherapy; TKI: Tyrosine kinase inhibitor.

Table 3 Key clinical trials evaluating selective internal radiation therapy (transarterial radioembolization) for hepatocellular carcinoma

Trial	Phase/design	Comparison	Primary endpoint	Results	Clinical insights
SARAH	Phase III, open-label, randomized controlled trial	SIRT (Y-90) vs Sorafenib	Overall survival (OS)	OS: 8.0 months (SIRT) vs 9.9 months (Sorafenib)- no significant difference. Fewer AEs and better QoL in SIRT group	Comparable efficacy with better safety; viable alternative in select patients
SIRveNIB	Phase III, open-label, randomized controlled trial	SIRT (Y-90) vs Sorafenib	OS	OS: 8.8 months (SIRT) vs 10.0 months (Sorafenib) no significant difference. Grade ≥ 3 AEs: 27.7% (SIRT) vs 50.6% (Sorafenib)	Reinforces safety advantage of SIRT; supports use in selected Asian patient populations
DOSISPHERE-01	Phase II, open-label, randomized controlled trial	Personalized SIRT vs Standard-dose SIRT	OS	OS: 26.6 months (personalized) vs 10.7 months (standard) P = 0.009. Higher response rates; some downstaged to surgery	Personalized dosimetry improves outcomes; highlights need for tailored treatment planning

AE: Adverse events; QoL: Quality of life; SIRT: Selective internal radiation therapy.

Table 4 A comparison between transarterial chemoembolization and transarterial radioembolization

Therapy	Vp2 PVTT	Vp3 PVTT	ORR (%)	Median OS (months)	Safety profile
TACE	Moderate	Moderate	50-70	18-24	Moderate
TARE	High	Moderate	60-80	22-30	Low

TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; PVTT: Portal vein tumor thrombus; ORR: Objective response rate; OS: Overall survival.