Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.

肝细胞癌术后预后模型的研究进展

[1]AdhouteX, PenarandaG, BronowickiJP, et al., 2015. Usefulness of the HKLC vs. the BCLC staging system in a European HCC cohort. J Hepatol, 62(2):492-493.

[2]AgopianVG, Harlander-LockeM, ZarrinparA, et al., 2015. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg, 220(4):416-427.

[3]AminMB, GreeneFL, EdgeSB, et al., 2017. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 67(2):93-99.

[4]BalachandranVP, GonenM, SmithJJ, et al., 2015. Nomograms in oncology: more than meets the eye. Lancet Oncol, 16(4):e173-e180.

[5]BolondiL, BurroughsA, DufourJF, et al., 2012. Heterogen

[6]eity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis, 32(4):348-359.

[7]BorzioM, DionigiE, RossiniA, et al., 2018. External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: a multicenter cohort study. Hepatology, 67(6):2215-2225.

[8]BrayF, FerlayJ, SoerjomataramI, et al., 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6):394-424.

[9]The Cancer of the Liver Italian Program (CLIP) investigators, 1998. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology, 28(3):751-755.

[10]The Cancer of the Liver Italian Program (CLIP) investigators, 2000. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology, 31(4):840-845.

[11]ChanACY, FanST, PoonRTP, et al., 2013. Evaluation of the seventh edition of the American Joint Committee on Cancer tumour-node-metastasis (TNM) staging system for patients undergoing curative resection of hepatocellular carcinoma: implications for the development of a refined staging system. HPB (Oxford), 15(6):439-448.

[12]ChanAWH, ChongCCN, MoFKF, et al., 2016. Applicability of albumin-bilirubin-based Japan integrated staging score in hepatitis B-associated hepatocellular carcinoma. J Gastroenterol Hepatol, 31(10):1766-1772.

[13]ChanAWH, ZhongJH, BerhaneS, et al., 2018. Development of pre- and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol, 69(6):1284-1293.

[14]ChanSL, MoFKF, JohnsonPJ, et al., 2011. Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population. J Gastroenterol Hepatol, 26(2):340-347.

[15]ChanSL, JohnsonPJ, MoF, et al., 2014. International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma: a joint United Kingdom and Hong Kong study. Chin J Cancer, 33(10):481-491.

[16]ChenLJ, ChangYJ, ChangYJ, 2021. Survival predictability between the American Joint Committee on Cancer 8th edition staging system and the Barcelona Clinic Liver Cancer classification in patients with hepatocellular carcinoma. Oncologist, 26(3):e445-e453.

[17]ChenWQ, ZhengRS, BaadePD, et al., 2016. Cancer statistics in China, 2015. CA Cancer J Clin, 66(2):115-132.

[18]ChunYS, PawlikTM, VautheyJN, 2018. 8th Edition of the AJCC Cancer Staging Manual: pancreas and hepatobiliary cancers. Ann Surg Oncol, 25(4):845-847.

[19]CongWM, BuH, ChenJ, et al., 2016. Practice guidelines for the pathological diagnosis of primary liver cancer: 2015 update. World J Gastroenterol, 22(42):9279-9287.

[20]di SandroS, CentonzeL, PinottiE, et al., 2019. Surgical and oncological outcomes of hepatic resection for BCLC-B hepatocellular carcinoma: a retrospective multicenter analysis among 474 consecutive cases. Updates Surg, 71(2):285-293.

[21]European Association for the Study of the Liver, 2018. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol, 69(1):182-236.

[22]FarinatiF, VitaleA, SpolveratoG, et al., 2016. Development and validation of a new prognostic system for patients with hepatocellular carcinoma. PLoS Med, 13(4):e1002006.

[23]FilgueiraNA, 2019. Hepatocellular carcinoma recurrence after liver transplantation: risk factors, screening and clinical presentation. World J Hepatol, 11(3):261-272.

[24]FornerA, ReigM, BruixJ, 2018. Hepatocellular carcinoma. Lancet, 391(10127):1301-1314.

[25]GianniniEG, MoscatelliA, PellegattaG, et al., 2016. Application of the intermediate-stage subclassification to patients with untreated hepatocellular carcinoma. Am J Gastroenterol, 111(1):70-77.

[26]GianniniEG, BucciL, GarutiF, et al., 2018. Patients with advanced hepatocellular carcinoma need a personalized management: a lesson from clinical practice. Hepatology, 67(5):1784-1796.

[27]GrandhiMS, KimAK, Ronnekleiv-KellySM, et al., 2016. Hepatocellular carcinoma: from diagnosis to treatment. Surg Oncol, 25(2):74-85.

[28]HalazunKJ, HardyMA, RanaAA, et al., 2009. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg, 250(1):141-151.

[29]HalazunKJ, NajjarM, AbdelmessihRM, et al., 2017. Recurrence after liver transplantation for hepatocellular carcin

[30]oma: a new MORAL to the story. Ann Surg, 265(3):‍557-564.

[31]HeW, PengBG, TangYQ, et al., 2018. Nomogram to predict survival of patients with recurrence of hepatocellular carcinoma after surgery. Clin Gastroenterol Hepatol, 16(5):756-764.e10.

[32]HouYF, WeiYG, YangJY, et al., 2016. Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC. Hepatobiliary Pancreat Dis Int, 15(4):378-385.

[33]HuoRR, LiuX, CuiJ, et al., 2020. Development and valid

[34]ation of a nomogram for assessing survival in patients with hepatocellular carcinoma after hepatectomy. Biosci Rep, 40(6):BSR20192690.

[35]JunCH, YoonJH, ChoE, et al., 2017. Barcelona clinic liver cancer-stage C hepatocellular carcinoma: a novel approach to subclassification and treatment. Medicine (Baltimore), 96(17):e6745.

[36]KamarajahSK, FrankelTL, SonnendayC, et al., 2018. Critical evaluation of the American Joint Commission on Cancer (AJCC) 8th edition staging system for patients with Hepatocellular Carcinoma (HCC): a Surveillance, Epidemiology, End Results (SEER) analysis. J Surg Oncol, 117(4):644-650.

[37]KimJH, ShimJH, LeeHC, et al., 2017. New intermediate-stage subclassification for patients with hepatocellular carcinoma treated with transarterial chemoembolization. Liver Int, 37(12):1861-1868.

[38]KollyP, ReevesH, SangroB, et al., 2016. Assessment of the Hong Kong Liver Cancer staging system in Europe. Liver Int, 36(6):911-917.

[39]KudoM, ChungH, OsakiY, 2003. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging score (JIS score). J Gastroenterol, 38(3):207-215.

[40]KulikL, El-SeragHB, 2019. Epidemiology and management of hepatocellular carcinoma. Gastroenterology, 156(2):477-491.e1.

[41]LeeYS, SeoYS, KimJH, et al., 2018. Can more aggressive treatment improve prognosis in patients with hepatocellular carcinoma? A direct comparison of the Hong Kong Liver Cancer and Barcelona Clinic Liver Cancer algorithms. Gut Liver, 12(1):94-101.

[42]LeungTWT, TangAMY, ZeeB, et al., 2002. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer, 94(6):1760-1769.

[43]LiaoMJ, SunJR, ZhangQF, et al., 2021. A novel post-operative ALRI model accurately predicts clinical outcomes of resected hepatocellular carcinoma patients. Front Oncol, 11:665497.

[44]MarreroJA, KulikLM, SirlinCB, et al., 2018. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology, 68(2):723-750.

[45]MazzaferroV, SpositoC, ZhouJ, et al., 2018. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology, 154(1):128-139.

[46]MorisD, ShawBI, McElroyL, et al., 2020. Using hepatocellular carcinoma tumor burden score to stratify prognosis after liver transplantation. Cancers (Basel), 12(11):3372.

[47]NanashimaA, SumidaY, MorinoS, et al., 2004. The Japanese integrated staging score using liver damage grade for hepatocellular carcinoma in patients after hepatectomy. Eur J Surg Oncol, 30(7):765-770.

[48]NanashimaA, SumidaY, AboT, et al., 2006. Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy. J Gastroenterol, 41(3):250-256.

[49]NoordzijM, LeffondréK, van StralenKJ, et al., 2013. When do we need competing risks methods for survival analysis in nephrology? Nephrol Dial Transplant, 28(11):2670-2677.

[50]OkudaK, ObataH, NakajimaY, et al., 1984. Prognosis of primary hepatocellular carcinoma. Hepatology, 4(S1):3S-6S.

[51]ParikhND, SingalAG, 2016. The ITA.LI.CA staging system: a novel staging system for hepatocellular carcinoma. PLoS Med, 13(4):e1002005.

[52]ParkS, ChoiS, ChoYA, et al., 2020. Evaluation of the American Joint Committee on Cancer (AJCC) 8th edition staging system for hepatocellular carcinoma in 1008 patients with curative resection. Cancer Res Treat, 52(4):1145-1152.

[53]QinW, WangL, HuBY, et al., 2019. A novel score predicts HBV-related hepatocellular carcinoma recurrence after hepatectomy: a retrospective multicenter study. J Gastrointest Surg, 23(5):922-932.

[54]ReigM, FornerA, RimolaJ, et al., 2022. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol, 76(3):681-693.

[55]SelbyLKF, TayRXY, WoonWWL, et al., 2017. Validity of the Barcelona Clinic Liver Cancer and Hong Kong Liver Cancer staging systems for hepatocellular carcinoma in Singapore. J Hepatobiliary Pancreat Sci, 24(3):143-152.

[56]ShindohJ, AndreouA, AloiaTA, et al., 2013. Microvascular invasion does not predict long-term survival in hepatocellular carcinoma up to 2 cm: reappraisal of the staging system for solitary tumors. Ann Surg Oncol, 20(4):1223-1229.

[57]SinnDH, ChoJY, GwakGY, et al., 2015. Different survival of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma patients by the extent of portal vein invasion and the type of extrahepatic spread. PLoS ONE, 10(4):e0124434.

[58]SuLH, ZhouT, ZhangZL, et al., 2016. Optimal staging system for predicting the prognosis of patients with hepatocellular carcinoma in China: a retrospective study. BMC Cancer, 16:1245.

[59]TabrizianP, JibaraG, ShragerB, et al., 2015. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg, 261(5):947-955.

[60]TellapuriS, SutphinPD, BegMS, et al., 2018. Staging systems of hepatocellular carcinoma: a review. Indian J Gastroenterol, 37(6):481-491.

[61]VernaEC, PatelYA, AggarwalA, et al., 2020. Liver transplantation for hepatocellular carcinoma: management after the transplant. Am J Transplant, 20(2):333-347.

[62]VitaleA, FarinatiF, NoaroG, et al., 2018. Restaging patients with hepatocellular carcinoma before additional treatment decisions: a multicenter cohort study. Hepatology, 68(4):1232-1244.

[63]WadaH, EguchiH, NodaT, et al., 2016. Selection criteria for hepatic resection in intermediate-stage (BCLC stage B) multiple hepatocellular carcinoma. Surgery, 160(5):1227-1235.

[64]WangCW, HeW, YuanYC, et al., 2020. Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy. Liver Int, 40(1):229-239.

[65]WangHB, LuZM, ZhaoXX, 2019. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J Hematol Oncol, 12:133.

[66]WangL, XianYT, YangZQ, 2019. Comparison of 10 prognostic staging systems in patients with advanced hepatocellular carcinoma. J BUON, 24(1):150-157.

[67]XuLL, LiL, WangP, et al., 2019. Novel prognostic nomograms for hepatocellular carcinoma patients with microvascular invasion: experience from a single center. Gut Liver, 13(6):669-682.

[68]XuW, LiRN, LiuF, 2020. Novel prognostic nomograms for predicting early and late recurrence of hepatocellular carcinoma after curative hepatectomy. Cancer Manag Res, 12:1693-1712.

[69]YanXP, FuX, CaiC, et al., 2015. Validation of models in patients with hepatocellular carcinoma: comparison of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging system in a Chinese cohort. Eur J Gastroenterol Hepatol, 27(10):1180-1186.

[70]YauT, TangVYF, YaoTJ, et al., 2014. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology, 146(7):1691-1700.e3.

[71]ZhangGQ, LiRF, ZhaoXY, et al., 2018. Validation of the American Joint Committee on Cancer eighth edition staging system in patients undergoing hepatectomy for hepatocellular carcinoma: a US population-based study. J Surg Res, 222:55-68.

[72]ZhangXP, WangK, WeiXB, et al., 2019. An Eastern Hepatobiliary Surgery Hospital microvascular invasion scoring system in predicting prognosis of patients with hepatocellular carcinoma and microvascular invasion after R0 liver resection: a large-scale, multicenter study. Oncologist, 24(12):e1476-e1488.

[73]ZhangZH, ShenSL, ChenB, et al., 2019. Hepatic resection provides survival benefit for selected intermediate-stage (BCLC-B) hepatocellular carcinoma patients. Cancer Res Treat, 51(1):65-72.

[74]ZhongJH, KeY, GongWF, et al., 2014. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg, 260(2):329-340.

[75]ZhouJ, SunHC, WangZ, et al., 2020. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer, 9(6):682-720.