Abstract
Introduction
The eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding
the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were
to reveal the defect and make updates.
Methods
Clinical and survival data of HCC patients from the Surveillance, Epidemiology, and
End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm
with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan–Meier method
and log-rank test were used to estimate differences in overall survival (OS). Three
propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration
of surgical treatment were performed. Cox regression was used to reveal risk factors.
Results
HCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS
in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had
increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence
interval [CI] = 1.06–1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01–1.37; P = 0.0283).
No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80–1.05;
P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84–1.01; P = 0.0888). Compared with T2aN0M0,
T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50–0.82; P = 0.0003) or PSM3
(HR = 0.63; 95%CI = 0.54–0.73; P < 0.0001). Cox regression analysis revealed that
surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3–0.4;
P < 0.001).
Conclusions
The current staging for T2N0M0 is imprecise because surgical treatment is not adequately
evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical
treatment was increased.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Surgical OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases.Hepatology. 2018; 68: 723-750
- Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.Int J Cancer. 2015; 136: E359-E386
- Primary liver cancer: worldwide incidence and trends.Gastroenterology. 2004; 127: S5-S16
- Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022
- Testosterone regulation of cyclin E kinase: a key factor in determining gender differences in hepatocarcinogenesis.J Gastroenterol Hepatol. 2016; 31: 1210-1219
- The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.Ann Surg Oncol. 2010; 17: 1471-1474
- Simplified staging for hepatocellular carcinoma.J Clin Oncol. 2002; 20: 1527-1536
- 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. 2013; 20: 1223-1229
- Validation of the 8th AJCC cancer staging system for pancreas neuroendocrine tumors using Korean nationwide surgery database.Cancer Res Treat. 2019; 51: 1639-1652
- Liver metastases of intrahepatic cholangiocarcinoma: implications for an updated staging system.Hepatology. 2021; 73: 2311-2325
- To use or not to use propensity score matching?.Pharmaceut Stat. 2021; 20: 15-24
- Propensity-score matching: optimal, adequate, or incomplete?.J Atr Fibrillation. 2018; 11: 2130
- Liver transplantation and liver resection for cirrhotic patients with hepatocellular carcinoma: comparison of long-term survivals.J Gastrointest Surg. 2018; 22: 840-848
- State-of-the-art surgery for hepatocellular carcinoma.Langenbeck's Arch Surg. 2021; 406: 2151-2162
- Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions.Semin Liver Dis. 2012; 32: 348-359
- Chinese clinical guidelines for the management of hepatocellular carcinoma: updates and insights.Hepatobiliary Surg Nutr. 2019; 9 (2020): 452-463
- Intermediate hepatocellular carcinoma: current treatments and future perspectives.Ann Oncol. 2013; 24: ii24-ii29
- Prognosis of hepatocellular carcinoma: the BCLC staging classification.Semin Liver Dis. 1999; 19: 329-338
- Effect of microvascular invasion on the prognosis in hepatocellular carcinoma and analysis of related risk factors: a two-center study.Front Surg. 2021; 8733343
- Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria.Ann Surg. 2011; 254: 108-113
- Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors.Ann Surg Oncol. 2008; 15: 1375-1382
- Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion.World J Surg. 2014; 38: 947-957
- Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing.Oncotarget. 2016; 7: 40481-40490
- Development and validation of a modified eighth AJCC staging system for primary pancreatic neuroendocrine tumors.Ann Surg. 2022; 275: e773-e780
- Modification of the 8th American Joint Committee on Cancer staging system for gallbladder carcinoma to improve prognostic precision.BMC Cancer. 2020; 20: 1129
- Propensity score matching: the 'devil is in the details' where more may Be hidden than you know.Am J Med. 2020; 133: 178-181
- Sublobar resection versus lobectomy for early-stage pulmonary carcinoid tumors ≤3 cm in size: a SEER population-based study.Ann Surg. 2020; 276e991-e999
Article info
Publication history
Published online: January 17, 2023
Accepted:
January 16,
2023
Received in revised form:
January 9,
2023
Received:
September 27,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
