Evolving practices, treatment decisions, and unmet needs in intermediate-stage hepatocellular carcinoma: An Asia Pacific perspective

Table 1 Hepatocellular carcinoma staging as defined throughout the survey[3,16]

	BCLC stage	Definition
Early HCC	BCLC-0	Single ≤ 2 cm lesion; preserved liver function; ECOG PS 0
	BCLC-A	Single or ≤ 3 nodules, each ≤ 3 cm; preserved liver function; ECOG PS 0
Intermediate HCC	BCLC-B1	Meets extended liver transplant criteria of institution; CPS 5-7; ECOG PS 0; ‘Up to 7’ in
	BCLC-B2	Well-defined nodules, preserved portal flow, selective access; CPS 5-7; ECOG PS 0; ‘Up to 7’ out
	BCLC-B3	Diffuse, infiltrative, extensive bilobar liver involvement; CPS 7; ECOG PS 0; ‘Up to 7’ out
Advanced HCC	BCLC-C	Vascular invasion and/or extrahepatic spread; preserved liver function; ECOG PS 1-2
End-stage HCC	BCLC-D	Any tumour burden; end-stage liver function; ECOG PS 3-4

BCLC: Barcelona Clinic Liver Cancer; HCC: Hepatocellular carcinoma; ECOG PS: Eastern Cooperative Oncology Group performance status; CPS: Child-Pugh score.

Table 2 Participant characteristics (n = 70), n (%)

	Overall (n = 70)	Korea (n = 10)	Malaysia (n = 10)	Philippines (n = 10)	Singapore (n = 10)	Taiwan (n = 10)	Thailand (n = 10)	Vietnam (n = 10)
Specialty
Medical oncologist	31 (44.3)	3 (30.0)	6 (60.0)	5 (50.0)	4 (40.0)	2 (20.0)	6 (60.0)	5 (50.0)
Gastroenterologist/hepatologist	24 (34.3)	6 (60.0)	-	3 (30.0)	4 (40.0)	7 (70.0)	2 (20.0)	2 (20.0)
Surgeon	7 (10.0)	-	2 (20.0)	1 (10.0)	2 (20.0)	1 (10.0)	-	1 (10.0)
Interventional radiologist	8 (11.4)	1 (10.0)	2 (20.0)	1 (10.0)	-	-	2 (20.0)	2 (20.0)
Healthcare setting
Public only	21 (30.0)	5 (50.0)	4 (40.0)	-	3 (30.0)	4 (40.0)	1 (10.0)	4 (40.0)
Private only	18 (25.7)	3 (30.0)	3 (30.0)	4 (40.0)	7 (70.0)	1 (10.0)	-	-
Both public and private	31 (44.3)	2 (20.0)	3 (30.0)	6 (60.0)	-	5 (50.0)	9 (90.0)	6 (60.0)
Primary institution
National or regional cancer centre	34 (48.6)	7 (70.0)	3 (30.0)	1 (10.0)	2 (20.0)	8 (80.0)	8 (80.0)	5 (50.0)
Large or mid-sized regional hospital	20 (28.6)	3 (30.0)	4 (40.0)	3 (30.0)	3 (30.0)	1 (10.0)	1 (10.0)	5 (50.0)
Private clinic/practice	12 (17.1)	-	2 (20.0)	4 (40.0)	5 (50.0)	1 (10.0)	-	-
Other	4 (5.7)	-	1 (10.0)	2 (20.0)	-	-	1 (10.0)	-
Role at primary institution
Junior doctor/resident	1 (1.4)	-	-	-	-	-	-	1 (10.0)
Consultant	34 (48.6)	-	9 (90.0)	9 (90.0)	6 (60.0)	-	2 (20.0)	8 (80.0)
Assistant/associate professor	22 (31.4)	4 (40.0)	2 (20.0)	2 (20.0)	1 (10.0)	3 (30.0)	8 (80.0)	2 (20.0)
Professor	16 (22.9)	5 (50.0)	1 (10.0)	1 (10.0)	2 (20.0)	6 (60.0)	1 (10.0)	-
Leadership position	29 (41.4)	4 (40.0)	3 (30.0)	5 (50.0)	2 (20.0)	5 (50.0)	3 (30.0)	7 (70.0)
Other	3 (4.3)	-	-	-	1 (10.0)	2 (20.0)	-	-
Licensed to prescribe systemic therapies for HCC	54 (77.1)	9 (90.0)	7 (70.0)	9 (90.0)	5 (50.0)	10 (100.0)	8 (80.0)	6 (60.0)
Leadership position in a medical society	17 (24.3)	3 (30.0)	2 (20.0)	3 (30.0)	2 (20.0)	2 (20.0)	2 (20.0)	3 (30.0)
Mean length of experience, years (SD)	18.0 (10.1)	16.3 (7.1)	12.9 (4.1)	15.5 (3.9)	21.4 (8.7)	24.7 (19.7)	17.8 (5.3)	17.3 (6.5)
Mean patients with HCC assessed annually, n (SD)	294.5 (604.9)	769.0 (971.0)	69.2 (80.9)	63.2 (54.2)	39.8 (39.3)	223.7 (264.7)	152.5 (164.5)	744.0 (942.6)
Mean total patients managed who have HCC, % (SD)	27.6 (26.2)	46.5 (28.1)	20.5 (23.1)	19.0 (19.2)	19.4 (22.3)	23.5 (20.0)	23.0 (24.3)	42.0 (29.3)

HCC: Hepatocellular carcinoma; SD: Standard deviation.

Table 3 Reported availability of national screening programmes and nature of diagnosis among survey responders (n = 70), n (%)

	Overall (n = 70)	Korea (n = 10)	Malaysia (n = 10)	Philippines (n = 10)	Singapore (n = 10)	Taiwan (n = 10)	Thailand (n = 10)	Vietnam (n = 10)
Respondents identifying availability of a national screening programme	N/A1	10 (100.0)	2 (20.0)	-	3 (30.0)	9 (90.0)	7 (70.0)	3 (30.0)
Usual location of HCC diagnosis
Large national hospital	40 (57.1)	5 (50.0)	6 (60.0)	3 (30.0)	8 (80.0)	7 (70.0)	5 (50.0)	6 (60.0)
Mid-sized hospital	21 (30.0)	2 (20.0)	4 (40.0)	3 (30.0)	2 (20.0)	3 (30.0)	5 (50.0)	2 (20.0)
Rural hospital	1 (1.4)	-	-	-	-	-	-	1 (10.0)
Private practice	4 (5.7)	1 (10.0)	-	3 (30.0)	-	-	-	-
Other	4 (5.7)	2 (20.0)	-	1 (10.0)	-	-	-	1 (10.0)
HCP usually diagnosing
GP/PCP	1 (1.4)	-	-	-	-	-	-	1 (10.0)
Medical oncologist	3 (4.3)	-	-	-	-	1 (10.0)	-	2 (20.0)
Gastroenterologist/hepatologist	54 (77.1)	10 (100.0)	6 (60.0)	8 (80.0)	10 (100.0)	9 (90.0)	8 (80.0)	3 (30.0)
Radiologist	8 (11.4)	-	2 (20.0)	2 (20.0)	-	-	2 (20.0)	2 (20.0)
Surgeon	3 (4.3)	-	2 (20.0)	-	-	-	-	1 (10.0)
Other	1 (1.4)	-	-	-	-	-	-	1 (10.0)
Mean estimated proportion of patients diagnosed by stage, %
Early stage (BCLC-0 or -A)	19.8	32.9	10.7	11.8	27.5	28.0	11.5	16.5
Intermediate stage (BCLC-B)	31.7	33.5	28.3	25.2	33.5	27.2	34.7	39.5
Advanced stage (BCLC-C)	32.8	26.6	36.0	39.0	26.0	32.3	40.3	29.5
End stage (BCLC-D)	15.6	7.0	25.0	24.0	13.0	12.5	13.5	14.5

¹Not applicable as data relate to availability of national screening programmes and are therefore country specific.

N/A: Not applicable; HCC: Hepatocellular carcinoma; HCP: Healthcare professional; GP: General practitioner; PCP: Primary care physician; BCLC: Barcelona Clinic Liver Cancer.

Table 4 Most important factors for improving the rate of early diagnosis of hepatocellular carcinoma among survey responders (n = 70), n (%)

Factors for improving the rate of early diagnosis	Responders (n = 70)
Patient education/awareness	58 (82.9)
Availability of a national screening programme	51 (72.9)
GP/PCP education	37 (52.9)
Reimbursement of diagnostic methods	31 (44.3)
Availability of specific imaging technologies	16 (22.9)
Specialist training	12 (17.1)
Improvement in turnaround time of laboratory or imaging results	4 (5.7)

GP: General practitioner; PCP: Primary care physician.

Table 5 Primary treatment decision makers in intermediate-stage hepatocellular carcinoma as identified by survey respondents and respondent guideline usage (n = 70), n (%)

	Responders (n = 70)
Primary treatment decision makers in iHCC
Surgeon	15 (21.4)
Gastroenterologist/hepatologist	31 (44.3)
Interventional radiologist	17 (24.3)
Medical oncologist	7 (10.0)
Guidelines used
EASL	45 (64.3)
AASLD	38 (54.3)
ESMO	36 (51.4)
NCCN	33 (47.1)
APPLE	22 (31.4)
ASCO	21 (30.0)
Local guidelines	31 (44.3)
Other	11 (15.7)

iHCC: Intermediate-stage hepatocellular carcinoma; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Disease; ESMO: European Society for Medical Oncology; NCCN: National Comprehensive Cancer Network; APPLE: Asia Pacific Primary Liver Cancer Expert; ASCO: American Society of Clinical Oncology.

Table 6 Multidisciplinary team availability and composition among survey responders (n = 70)

	Responders
Access, n (%)
Within hospital	66 (94.3)
Within country (e.g., in collaboration with another institution)	43 (61.4)
MDTs incorporating given specialty, n/N (%)
Medical oncologist	59/68 (86.8)
Interventional radiologist	65/68 (95.6)
Gastroenterologist/hepatologist	64/68 (94.1)
Surgeon	66/68 (97.1)
Nurse	19/68 (27.9)
Project coordinator/administrator	19/68 (27.9)
Patient liaison/educator	9/68 (13.2)
Other	12/68 (17.6)

MDT: Multidisciplinary team.

Table 7 Preferred first-line treatment choices by Barcelona Clinic Liver Cancer substage among survey responders (n = 70), n (%)

Preferred first-line treatment choice	BCLC-B1	BCLC-B2	BCLC-B3	BCLC-C
C-TACE	27 (38.6)	27 (38.6)	4 (5.7)	1 (1.4)
DEB-TACE	5 (7.1)	9 (12.9)	5 (7.1)	-
TARE	9 (12.9)	10 (14.3)	4 (5.7)	3 (4.3)
Ablation	2 (2.9)	-	-	-
Resection	20 (28.6)	3 (4.3)	-	-
Systemic therapy alone	1 (1.4)	4 (5.7)	39 (55.7)	51 (72.9)
Systemic therapy in combination/sequence with LRT	5 (7.1)	16 (22.9)	17 (24.3)	13 (18.6)

BCLC: Barcelona Clinic Liver Cancer; C-TACE: Conventional transarterial chemoembolization; DEB-TACE: Drug-eluting beads transarterial chemoembolization; TARE: Transarterial radioembolization; LRT: Locoregional therapy.

Table 8 Experience of using systemic therapies in combination/sequence with locoregional therapy for the treatment of intermediate-stage hepatocellular carcinoma among all Asia Pacific prescribers (n = 54)

	Lenvatinib	Sorafenib	Pembrolizumab + lenvatinib	Atezolizumab + bevacizumab	Durvalumab + bevacizumab	Durvalumab + tremelimumab	Other	None of the above
Respondents with experience of using systemic therapy in combination/sequence with LRT, n (%)	51 (94.4)	24 (44.4)	14 (25.9)	37 (68.5)	11 (20.4)	19 (35.2)	3 (5.6)	1 (1.9)
LRTs used in combination with systemic therapy, n/N (%)
C-TACE	43/47 (91.5)	17/18 (94.4)	11/12 (91.7)	28/32 (87.5)	9/10 (90.0)	14/18 (77.8)	-	-
DEB-TACE	20/47 (42.6)	6/18 (33.3)	6/12 (50.0)	15/32 (46.9)	2/10 (20.0)	10/18 (55.6)	-	-
TARE	7/47 (14.9)	3/18 (16.7)	1/12 (8.3)	11/32 (34.4)	-	1/18 (5.6)	-	-
Other radiotherapy	8/47 (17.0)	2/18 (11.1)	1/12 (8.3)	6/32 (18.8)	-	1/18 (5.6)	-	-
Ablation	10/47 (21.3)	2/18 (11.1)	1/12 (8.3)	11/32 (34.4)	1/10 (10.0)	2/18 (11.1)	-	-
Timing of systemic therapy use in relation to TACE, n/N (%)
Pre-TACE	14/44 (31.8)	3/17 (17.6)	4/12 (33.3)	7/31 (22.6)	-	4/16 (25.0)	-	-
Peri-TACE	16/44 (36.4)	7/17 (41.2)	3/12 (25.0)	5/31 (16.1)	4/10 (40.0)	5/16 (31.3)	-	-
Post-TACE	12/44 (27.3)	6/17 (35.3)	4/12 (33.3)	18/31 (58.1)	6/10 (60.0)	6/16 (37.5)	-	-
Other	2/44 (4.5)	1/17 (5.9)	1/12 (8.3)	1/31 (3.2)	-	1/16 (6.3)	-	-

LRT: Locoregional therapy; C-TACE: Conventional transarterial chemoembolization; DEB-TACE: Drug-eluting beads transarterial chemoembolization; TARE: Transarterial radioembolization; TACE: Transarterial chemoembolization.