Approximately one‐half of patients with early‐stage hepatocellular carcinoma meeting Milan criteria did not receive local tumor destructive or curative surgery in the post‐MELD exception era

Abstract

BACKGROUND: Since 2002, priority Model for End-stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long-term survival rates among patients with HCC tumors meeting the Milan criteria in the post-MELD exception era. METHODS: The current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 43% of patients did not receive any specific therapy. Overall, the 5-year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%-27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be dependent on age, race=ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race=ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03-1.47 [P 5.02]), whereas Asian=Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [P <.001]). CONCLUSIONS: Despite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5-year relative survival rates, especially among black patients. Cancer 2014;120:1725-32. V C 2014 American Cancer Society.KEYWORDS: SEER, survival analysis, liver transplantation, localized hepatocellular carcinoma, Model for End-stage Liver Disease. INTRODUCTIONHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. 1,2 It is the fifth leading cause of cancer in men and the seventh leading cause of cancer in women in United States. 3,4 Although incidence rates for most cancers in United States are declining, incidence rates for HCC in both men and women continue to rise. 3 It is estimated that there will be 30,640 new HCC cases diagnosed in 2013 (22,720 in men and 7920 in women). 3 Similarly, mortality rates for HCC have also increased over the past 2 decades and it is estimated that there will be 21,670 HCC-related deaths in 2013 (14,890 in men and 6780 in women). 3 Despite advances in screening and early detection, HCC still has a poor overall 5-year survival rate of 16% according to the data published by the Surveillance, Epidemiology, and End Results (SEER) program between 2002 and 2008. 3

Association of Provider Specialty and Multidisciplinary Care With Hepatocellular Carcinoma Treatment and Mortality

“…Limited comparison can also be made to the US SEER-Medicare HCC cohort from 2000–2007 reported by Shaya et al 12 SEER-Medicare does not report BCLC staging because of the absence of data on liver disease severity and performance status, but the HRs we report for survival with resection, transplantation, and liver-directed therapy are highly comparable to those observed in SEER-Medicare enrollees. In later reports from the SEER registry, 30 the overall 5-year survival rate for patients within Milan criteria of 39 months was slightly higher than the BCLC 0/A patients in our cohort (38months and 28 months, respectively) but some of this difference could be explained by lower median age, higher frequency of Asian patients (more likely to have noncirrhotic HCC caused by HBV), higher frequency of female patients, and biases related to requirements for histologic confirmation in that cohort. Again, the HRs for individual interventions in that study were highly comparable to the present study, with adjusted HRs associated with transplantation (0.12), resection (0.25), and locoregional therapy (0.54).…”

“…42 In SEER-Medicare patients in 2000–2007, fewer than 40% underwent any HCC-directed interventions, likely because of age and comorbidities. 12 Later SEER registry data 30 also demonstrate very low treatment rates, even for early stage HCC in US patients, with 43% of patients within Milan criteria not undergoing surgery, ablation, or transplantation. Thus, the non-treatment rates we observed are slightly lower than those observed in similar cohorts.…”

Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis

“…However, even in early‐stage patients, these potentially curative treatments have drawbacks and contraindications depending on the size and location of the tumor, the patient's baseline liver function, and the presence of comorbid conditions . Consequently, 43% of patients did not receive any of these treatments in a previously reported cohort study …”

A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy

“…20 Similarly, other publications show a underutilization of surgical therapy in patients with HCC. 21 There is a clear public health need to increase curative and life prolonging HCC interventions in the SEER-Medicare population.…”