High Center Average Case Volume Associated With Improved Survival for Patients With Hepatocellular Carcinoma

Abstract

The association between higher surgical case volume and improved survival outcomes is well documented for several cancer types. However, it is yet unknown whether patients treated at centers that see more cases of hepatocellular carcinoma (HCC) per year have improved overall survival (OS). This is a retrospective analysis of data from the Commission on Cancer’s National Cancer Database (NCDB) from 2004-2014. 154,408 patients with liver cancer were identified (International Classification of Diseases for Oncology 3rd edition disease topography code C22). Of these, 135,442 patients had histopathologic type HCC (malignant behavior code 8170/1). 53,829 patients were excluded from the analysis on the basis of stage IV disease (N=24,200) and incomplete staging information (N=29,629). This left 81,647 patients for analysis. Annual case volume was calculated by taking the total number of cases treated per center over the 10 year period and dividing by 10. Subsequently, annual case volume was separated into quartiles for analysis. Univariate and multivariate analyses were performed using Cox regression analysis to determine factors associated with improved OS. Factors with a P<.2 on univariate analysis were retained in the multivariate model (data not shown). Bonferroni correction was applied, and as 15 factors were tested for significant association, p-values were considered significant if <.003. Kaplan-Meier curves and log-rank tests were also used to calculate and compare OS estimates. A total of 81,647 patients with non-metastatic HCC were treated at a total 1218 centers. The median [range] HCC case volume per year averaged over the 10 year study period was 48.6 [0.1-205.5]. Centers in the 1st, 2nd, 3rd and 4th quartiles by volume treated between 0.1-11.35, >11.35-48.6, >48.6-60, and >60-205.5 patients per year, respectively. Median survival for patients treated in 1st, 2nd, 3rd and 4thquartile centers by annual case volume were 7.3, 12.8, 24.6 and 28.7 months, respectively; 2-year OS were 24.4%, 35.2%, 50.7% and 54.3%, respectively (Log Rank p<.001). In a multivariate model that included sex, age, race, Charlson Comorbidity Score, alpha-fetoprotein, creatinine, bilirubin, international normalized ratio, tumor size, tumor stage, community vs academic institution, insurance type, median household income and initial treatment modality, institutional annual HCC case volume remained significantly associated with improved OS when analyzed as a continuous variable (unit hazard ratio 0.997 [95% confidence interval 0.9965-0.9976]; p<.001). Higher annual HCC case volume at the treating institution is significantly associated with improved OS for patients with HCC. Although the selection bias of patients who present to high volume centers cannot be excluded, improved OS may be related to access to multidisciplinary evaluation, option of varied treatment modalities, and increased subspecialty expertise.