Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis

Gastric neuroendocrine neoplasms (G-NENs) comprise a heterogeneous collective of tumours arising from the enterochromaffin-like cell, and account for approximately 7% of all neuroendocrine neoplasms [1]. In the past few decades, statisticians have witnessed a tenfold rise in the incidence of G-NEN, possibly due to progressed endoscopic screening skills and increased pathologic experience [2, 3]. G-NEN can be subdivided into three subtypes: type I associated with autoimmune atrophic gastritis, type II associated with Zolinger-Ellison syndrome/gastrinoma, and type III occurring sporadic without hypergastrinemia [4].

Nowadays, many clinicians and nurses mainly focused on clinicopathological characteristics, without taking the impact of psychological and social factors into consideration. In reality, these sociopsychological factors do have an influence on patient outcomes [5]. Marriage is one of the most important source of social support, which affects physical health through integrative physiological mechanisms [6]. Previous studies have pointed out that married patients tend to have better survival outcome in several cancer types [7‐15]. However, whether marriage has a “protective” effect for G-NEN patients has not yet been established. In the present study, we examined the data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry database to assess the effects of marital status on outcomes of patients with G-NEN.

In this study, we assessed the impact of marital status at diagnosis on survival outcomes in a SEER cohort of G-NEN patients. Based on relatively large sample size and PS-matched dataset, our study provided results with high validity and reliability. Being married was indicated to exert a protective effect on survival compared to any unmarried status.

The diagnosis of cancer exposes an individual to chronic psychosocial stress, which triggers fight-or-flight responses by activating the hypothalamic-pituitary-adrenal axis. From a physiology perspective, psychological stress increases epinephrine, prostaglandins, and glucocorticoid levels, and reduces NK cells and cytotoxic T cells activity [17‐19]. Then stress induces immune suppression, contributing to tumour proliferation, progression, and metastasis [20, 21]. A cell line study of ovarian cancer demonstrated that stress hormones can also enhance the capacity of tumour cells to invade the extracellular matrix, contributing to tumour metastasis [22]. The detailed mechanism for protective role of marriage on neuroendocrine tumours might be explored in further experimental studies. Typically, oncological patients deny, feel angry, bargain, experience depression, and then gradually accept the reality. Social support, or supportive social network, is greatly needed throughout this process. With emotional support of their spouse, married patients experience less stress and despair [23]. Additionally, patients with less psychosocial stress have better compliance to medical recommendations [24]. Spousal encouragement may increase G-NEN patients’ willingness to survive, and they are more likely to receive treatments like surgery and/or chemotherapy.

With the transformation from biomedical model to biopsychosocial model of illness [25], the importance of sociopsychological factors on oncological diseases has gained increasing attention. Positive psychosocial factors can alleviate the pain and worries of cancer patients, thus improving the treatment compliance, treatment effect, quality of life and survival rate. Therefore, it is of great significance to fully understand the relationship between prognosis of tumour patients and psychosocial factors and to monitor the psychological changes of tumour patients. Sociopsychological factors, including marital status, can impact tumour development and survival of oncological diseases through the regulation of endocrine and immune systems. Our results show that all unmarried groups showed poorer survival outcome compared with the married group, but windowed G-NEN patients have the poorest prognosis, which is also demonstrated in studies regarding gastrointestinal stromal tumour, gastric cancer, nasopharyngeal carcinoma, and rectal cancer [26‐29]. Single and separated G-NEN patients tend to be more prepared to build social support networks other than marriage compared to widowed patients. As such, clinicians, nurses, and health care workers need to pay more attention to widowed patients’ emotional need, communicate more with the widowed, and provide them with necessary social support in clinical practice.

Despite of the strengths of this study including large sample size, subgroup analysis, and PS-matching method, there were some potential limitations. First, we ignored effect of the quality of marital life among G-NEN patients in the analysis. This may cause bias since unsatisfactory marriage can result in immune dysregulation [30]. Previous study revealed that marital relationship may change after cancer diagnosis [31]. The SEER database did not provide information on change of marital status after G-NEN diagnosis. Another notable drawback was the inability to classify patients according with the clinical subgroups (Type I, II, III) according with international guidelines [16], where type III tumour showed markedly worse outcome than others. Since type I and II of G-NENs comprise vast majority of well-differentiated tumours in general, and most type III tumour can be classified into poorly-differentiated neuroendocrine carcinoma, we tried to compensate for this limitation by validating the prognostic effect of marital status in well-differentiated tumours only. Besides, we failed to adjust some recognized prognostic parameters such as chemotherapy and radiation in the regression model due to lack of detailed information in the database.

In addition to marital status, many other socioeconomic factors (e.g. household income and medical insurance status) and sociopsychological factors may also play a role in G-NEN patients’ outcomes, which warrant further investigation. Moreover, further in-depth investigations according with different G-NEN types are needed to better understand the meaning of the findings in the present study.

In summary, our study found that marital status was an independent prognostic factor among G-NEN patients, and married individuals enjoyed significant survival benefits than those unmarried. Particularly, widowed G-NEN patients suffer the highest mortality risk. It is necessary to provide timely psychological intervention and social support for unmarried, especially widowed G-NEN patients in clinical practice. However, our results should be interpreted with caution since the inability to classify patients into the three clinical types of G-NEN in this study.