Epidemiology & First option of treatment Do Young Kim Department of Internal Medicine, Yonsei University College of Medicine

Epidemiology

High HCC incidence in Eastern Asia Source: GLOBOCAN 2008

Top 10 Cancer incidence in Korea: 2012

HCC; incidence and prevalence Source: 2012 National Cancer Statistics (2014)

Trend of age-standardized incidence of HCC (1999-2012)

Trends of incidence and mortality in HCC (Age-standardized) Source: National Cancer Statistics (2013)

5-year survival rates of major cancers in Korea The 5-year survival rate is still very poor, and the median survival time of HCC patients is only about 2-years. Thus, the incidence rate of HCC is almost equals to the mortality rate. Stomach Lung Colon Liver Thyroid Breast Ut. Cx Biliary Pancreas Prostate

Korean nationwide HCC registry data

Courtesy of Dr. Lim YS

Methods Total HCC Registry (2003-2005) 31,521 Random Sample Sample (N) 5,252 16.7% Abstraction Possible 4,630 14.7% 88.2% Real Abstraction* 4,522 14.3% 86.1% KLCSG Voluntary Report Report (N) Analysis (%) Total Report 4,578 14.5% Analysis Possible* 4,311 13.7% 94.4% * Exclusions for miss-Dx, duplication, miss-data Courtesy of Dr. Lim YS

HCC characteristics - Age & Gender- P = 0.41 % Random Voluntary P Age 57.1 ± 10.8 56.8 ± 10.7 0.14 100 80 Female 60 Male 40 20 Random Voluntary Courtesy of Dr. Lim YS

Liver function & Tumor stage Child-Pugh Class TNM Stage (UICC v.6) P<0.001 P<0.001 100% 100% 80% 80% IV 60% 60% C III B II 40% A 40% I 20% 20% 0% 0% Random Voluntary Random Voluntary Courtesy of Dr. Lim YS

Cause & Treatment Associated Disease First Treatment P<0.001 100% 100% 80% 80% Systemic Tx 60% Others 60% EBRT Alcohol Transarterial Tx HCV Local Ablation 40% HBV 40% LT Resection 20% 20% 0% 0% Random Voluntary Random Voluntary Courtesy of Dr. Lim YS

Overall survival Survival Years after Diagnosis Voluntary Reporting (median surv. 29 mo.) % 100 Random Statutory (median surv. 17 mo.) 80 66.6% 60 53.6% 44.6% Survival 54.9% 38.6% 40 32.9% 42.5% 35.0% 31.1% 29.6% 20 P<0.001 1 2 3 4 5 Years after Diagnosis Courtesy of Dr. Lim YS

First option of treatment

HCC staging: AASLD guidelines (updated 2010) RFA Sorafenib Stage 0 PST 0, Child–Pugh A Very early stage (0) 1 HCC < 2 cm Carcinoma in situ Early stage (A) 1 HCC or 3 nodules < 3 cm, PST 0 End stage (D) Liver transplantation TACE Resection Symptomatic treatment (20%) Survival < 3 months Curative treatments (30%) 5-year survival 40–70% Palliative treatments (50%) Median survival 11–20 months Associated diseases Yes No 3 nodules ≤ 3 cm Increased Normal 1 HCC Stage D PST > 2, Child–Pugh C Intermediate stage (B) Multinodular, PST 0 Advanced stage (C) Portal invasion, N1, M1, PST 1–2 Stage A–C PST 0–2, Child–Pugh A–B HCC Portal pressure/ bilirubin Adapted from Bruix J, Sherman M. Hepatology. 2010. http://www.aasld.org/practiceguidelines/Documents/ Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf. Llovet JM, et al. J Natl Cancer Inst. 2008;100:698–711. AASLD = American Association for the Study of Liver Diseases; PEI = percutaneous ethanol injection; PST = Performance Status test; RFA = radiofrequency ablation.

APASL guidelines HCC Confined to the liver Main portal vein patent Extrahepatic metastasis Main portal vein tumor thrombus Resectable Child–Pugh A/B Child–Pugh C Yes No Solitary tumor ≤ 5 cm ≤ 3 tumors ≤ 3 cm No venous invasion Tumor > 5 cm > 3 tumors Invasion of hepatic/portal vein branches Child–Pugh A Child–Pugh B Sorafenib or systemic therapy trial Resection/RFA (for < 3 cm HCC) Local ablation Transplantation TACE Supportive care APASL recommendations on HCC. Omata M, et al. Hepatol Int. 2010;4:439–74.

Japan Society of Hepatology: consensus-based treatment algorithm for HCC Extrahepatic spread No Yes Liver function Child–Pugh A/B Child–Pugh C Child–Pugh B/C Child–Pugh A Vessel invasion No Yes No Yes Number Single 1–3 4 or more Within Milan criteria and age ≤ 65 Within Milan criteria and age ≤ 65 Exceeding Milan criteria or age > 65 Hypovascular early HCC Size ≤ 3 cm > 3 cm Intensive follow-up Ablation Resection Ablation Resection TACE (TACE + ablation) TACE HAIC (resection + ablation) Transplantation (TACE/ablation for Child–Pugh C patients) Sorafenib HAIC TACE Resection Transplantation (TACE/ablation for Child–Pugh C patients) Palliative care Sorafenib Treatment Sorafenib (TACE refractory) TAI = hepatic arterial infusion chemotherapy. Kudo M, et al. Dig Dis. 2011;29:339–364.

First-line treatment option in each mUICC stage

Single, less than 2cm HCC, Child-A, no or minimal portal hypertension (BCLC-0) Resection vs. RFA; many studies LT?

Single, more than 2cm HCC (BCLC-A) In case within Milan criteria

Multiple, less than 2cm HCC (BCLC-A or B) In case above Milan criteria

Single, less than 2cm HCC with vascular invasion (BCLC-C) According to Western guidelines Unusual presentation. Practically TACE preferred, Resection vs. TACE?

Multiple, more than 2cm HCC (BCLC-B or A) Mostly TACE, LT or RFA: limitedly applied

Hong Kong Liver Cancer (HKLC) classification Yau T, et al. Gastroenterology 2014

Single, more than 2cm HCC with vascular invasion (BCLC-C) Which modality is the best for this kind of HCC? No data

Multiple, less than 2cm HCC with vascular invasion (BCLC-C) Resection TACE may be preferred because of small tumor size

Advanced HCC without extrahepatic spread (BCLC-C) Only sorafenib has evidence.

Competitor (I)

Competitor (II)

Competitor (III) Gastroenterology 2010

HCC with extrahepatic spread (BCLC-C)

Conclusions HCC incidence in Korea is slightly decreasing. Still a major cancer related with significant mortality Prognosis is being improved due to proper management Selection of first treatment option does not always depend on evidence. Guideline are just guidelines. Heterogeneity of HCC presentation makes it difficult to keep algorithm for selecting treatment option.

Thank you for attention