The impact of socioeconomic status (SES) on the prognosis and clinical management of cancer patients had received more attention. Several investigations[10–12] indicated SES disparities, such as marital status, insurance status and household income were associated with the cancer stage at diagnosis and survival outcome of patients with HCC. However, as far as we know, few studies had investigated more than three SES factors in one research and not involved into TNM sating system as an independent parameter. In this large-scale study, four SES factors (insurance status, marital status, country percentage with bachelor degree and country-level median household income) associated with CSS of patients with HCC were identified to construct a SES stage which divided the eligible patients into SES-1stage (higher socioeconomic status) and SES-2 stage (lower socioeconomic status). Subsequently, a superior staging system was generated to predictive prognosis by combining the TNM stage and the SES stage.
One previous study based on a large population of more one million cancer patients in the United States indicated that unmarried patients had higher risk of presentation with metastasis, under-utilization of definitive treatment and unfavorable survival outcome, compared with married patients. Several investigations[14–16] also demonstrated that marital status was significantly associated with prognosis in HCC and other cancers. In line with these studies, our results also showed that patients of never married, divorced and widowed had higher risk of mortality (all p values < 0.001). The favorable survival of married patients may be explained by the emotional support by spouse and the better financial situation, which may bring about better prognosis. It was reported[17–19]that unmarried patients experienced more stress and depression and worse survival, compared to married patients. Otherwise, one study found that depression and anxiety were significantly associated with breast cancer recurrence. In the meantime, married patients had better obedience to the prescribed surveillance and treatment than unmarried patients, which may result into higher rate of recurrence and worse prognosis[21–23].
The insured status and higher household income reflected better financial status to cope with the increasing cost of health care. Several previous studies[12, 24, 25] demonstrated that patients with Medicaid and uninsured and lower household income had more advanced HCC tumor stage and unfavorable survival of patients with HCC. Patients with poor financial status experienced delays in access to regular HCC surveillance and were likely to received surgery and transplantation[26–28], which may explain the worse prognosis of these patients.
As we expected, the education disparities have an impact on lifestyle, health care and disease surveillance and treatment[29–31]. The higher education patients with HCC were younger than the less education patients due to more active health management. Several studies[9, 24] demonstrated that less education was significantly correlated with under-utilization of HCC surveillance and effective treatment, more advanced disease and unsatisfactory survival.
Recently, the correlation of socioeconomic status and the health of population had received more attention. Socioeconomic status is an important factor of the heath inequality, as a very robust positive association between socioeconomic status and health was confirmed. And socioeconomic status was correlated with not only cancer disease but also chronic stress, heart disease, ulcers, type 2 diabetes. We constructed SES stage to divide the eligible patients into SES-1stage (higher socioeconomic status) and SES-2(lower socioeconomic status) stage by using HRs of four SES factors associated with CSS. In our analysis, higher SES patients were likely to have early stage HCC and receive surgery, transplantation and chemotherapy. After adjusting for several confounders, such as age, race, sex and tumor stage, disparity of SES was significantly associated with CSS of patient with HCC. The explanation of this result is the combined influence of four aforementioned factors.
Traditional AJCC TNM staging system was widely used to stratify patients for treatment selection and prognosis prediction in clinical practice. However, this algorithm only focused the clinicopathological features of tumor and not concerned the socioeconomic status. As shown in our results, lower SES stage revealed a 32.0% increased risk of CSS, compared to higher SES stage, indicating that SES was a significant prognostic predictor of survival. The C-index of TNM-SES stage was higher than that of TNM stage (0.735 vs 0.718),indicating a superior predictive value. The vast majority of higher SES stage patients (expect IIIC) showed better prognosis in comparison with those who had lower SES stage in the same TNM stage. However, it was be noted that there was no statistical difference in IIIC stage patient in terms of SES ༈p < 0.384). This result may be explained by the following reason. Firstly, relatively insufficient patients with IIIC stage may make statistical bias, which covered up the prognostic value of SES, compared with patients with other stages. Besides, IIIC HCC stage is characterized by Tumor with direct invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum. As represented in our study, the HRs of IIIC stage was higher than that of IVA stage in same SES stage, indicating the worse prognosis of patient with IIIC stage. The aggressive biological factors of IIIC stage may impaired the effect of SES on survival. Interestingly, a higher HR was observed in patients with NBF1 stage compared with patients who had NBF0 stage and more TNM sage, which revealed the superior prognostic value of SES stage. It was worthy to mentioning that there was no significant difference of HRs among the IIIB, III and IV in corresponding SES stage, and even the higher HRs were observed in stage IIIB than stage IVA in both SES stage. This result demonstrated that direct invasion of adjacent organs and lymph node metastasis may not have meaningful effect on survival of patient on HCC. It was reported in several studies[34–36] that microvascular invasion was associated with unfavorable prognosis.
This large population-based information from the SEER database enhanced the generalizability and creditability of our investigation. However, it should be noted that there were several limitations in our study. Firstly, the SES only incorporated five factors (insurance status, marital status, country percentage with bachelor degree, country-level median household income and country percentage with employed) and attained four factors associate with CSS of patient with HCC in our study. Actually, SES also included other elements, such as religion, occupation and wealth, which were not registered in SEER database. Secondly, the TNM staging system registered in SEER database was not specific for HCC and not commonly used in clinical practice. The burden of tumor, hepatic function and microvascular invasion also played a critical role in survival outcome of HCC, which was lacked in SEER database. Finally, there was not information of transcatheter arterial chemoembolization (TACE) and systemic therapy in SEER database, which was an important treatment for unresectable HCC. Despite with these limitations, our large-scale comprehensive investigation revealed a significant effect of SES on staging, prognosis and clinical management for HCC.