In this population-based study, we utilized the SEER database to conduct a comprehensive examination of the clinical characteristics and prognostic outcomes of AYA diagnosed with PNETs. Our findings revealed notable differences between the AYA and OA groups, highlighting the distinct clinical manifestations of PNETs in the younger population. Compared to the OA group, the AYA cohort exhibited a higher proportion of females, earlier clinical staging, reduced distant metastasis rates, and significantly increased surgical treatment rates. These observations suggest that AYA patients with PNETs tend to present with less advanced disease states and have improved access to surgical procedures. This may be attributed to early disease detection or a more proactive therapeutic approach adopted for this age group. Our findings align with previous studies by Mei et al. (18) and Shi et al. (19), which also reported a higher proportion of surgical treatments in the young group compared to the elderly. Furthermore, our study found that the proportion of black patients with PNETs was higher among young patients than elderly patients, consistent with the research by Shi et al. (19) and Goksu et al. (20).
Additionally, we observed an upward trend in the incidence rate of PNETs among AYA patients. Similar trends have been reported by Goksu et al. (20) and Yadav et al. (21), indicating a rising incidence of PNETs among young individuals. The increasing incidence of PNETs among AYAs may be partially explained by advancements in medical technology and diagnostic methods. Modern imaging techniques, such as endoscopic ultrasonography, CT, and MRI, have enhanced the accuracy of PNET detection and diagnosis. Moreover, societal changes, including increased work stress and lifestyle choices among young people, may also contribute to the rising incidence of PNETs to some extent.
Previous studies have consistently demonstrated that age plays a crucial role in determining the prognosis of patients with PNETs, with younger patients exhibiting a more favorable prognosis (22–24). In our investigation, we specifically targeted the AYA population and discovered notable differences between the AYA and OA groups. Specifically, the AYA group presented significantly higher mean 1-, 3-, and 5-year OS and CSS rates compared to the OA group (P < 0.05) (Table 2). Furthermore, our analysis indicated that the AYA group had better OS (P < 0.05) and CSS (P < 0.05) outcomes compared to the OA group (Figs. 3 and 4). Both univariate and multivariate Cox regression analyses supported the finding that age is an independent prognostic factor in patients with PNETs (Supplementary Tables 2 and 3). Additionally, through multivariate Cox regression analysis, we identified sex, N stage, tumor size, surgery, and chemotherapy as significant prognostic factors for OS in the AYA group. Similarly, sex, N stage, surgery, and chemotherapy were found to be prognostic factors for CSS (Tables 3 and 4).
Previous research has indicated that PNETs are predominantly found in males in France, the United States, and Norway (25). In this study, there were 6462 male patients (55.1%) and 5266 female patients (44.9%), similarly showing a higher proportion of male patients. However, we found that among the AYA population, the proportion of female PNETs was higher than that of male patients (55.2% vs. 44.8%). The higher incidence of PNETs in young female patients compared to males may be attributed to a combination of factors. Specifically, women's physiological characteristics and genetic predispositions may make them more susceptible to this disease. Moreover, the lifestyle choices, dietary habits, and potential environmental exposures specific to modern young women might also increase their risk. Furthermore, the mental stress faced by women, coupled with their tendency to prioritize health management and actively participate in early screening compared to men, might contribute to the higher reported incidence of PNETs among women in statistical data. However, further clinical research and epidemiological studies are needed to validate these hypotheses.
In this study, we found that the risk of death in AYA patients with lymph node metastasis (LNM) was more than three times higher than that in patients without LNM (Tables 3 and 4). Studies by Krampitz et al. (26) and Curran et al. (27) also showed that patients with PNETs and LNM had a poorer prognosis. The poor prognosis of patients with PNETs and LNM is primarily due to the fact that LNM signifies the spread of the tumor, indicating disease progression and deterioration. Simultaneously, it affects the normal immune function of the lymphatic system, reducing the body's resistance and making the tumor more prone to spread throughout the body. Furthermore, LNM implies that the tumor may have stronger invasive and metastatic capabilities, which not only increases the likelihood of metastasis to other organs but also limits treatment options and increases the difficulty of treatment. These factors combined contribute to the poor prognosis of patients with PNETs and LNM. Surgery is the preferred treatment for PNETs, especially for early-detected tumors. The type of surgery depends on the location and size of the tumor. Depending on the specific situation, options such as tumor resection, distal pancreatectomy, and pancreaticoduodenectomy can be chosen. Surgical treatment can improve the prognosis of patients with PNETs (28–30). In this study, we also found that surgical treatment can improve the prognosis of AYA patients with PNETs.
The limitations of this study include several aspects. Firstly, the data sourced from the SEER database might not encompass all cases of PNETs, especially those undiagnosed or unreported, and there may be input errors or incomplete data entries. Secondly, the study population primarily represents the United States, limiting the generalizability of the findings to other global regions. Thirdly, as a retrospective database study, the accuracy and completeness of data collection may be affected. Fourthly, despite considering various demographic and clinical variables, there may be additional factors such as lifestyle, family history, or genetic mutations that could influence patient outcomes. Lastly, the study mentioned the impact of surgery and chemotherapy on prognosis, but did not delve into the differences in effectiveness between various surgical methods or chemotherapy regimens, which may affect the accuracy of prognosis evaluation for patients.
In conclusion, this SEER database study found that AYA with PNETs have distinct clinical characteristics and a better prognosis than OA. AYA tend to present with earlier staging and lower metastasis, benefiting more from surgical treatment. Sex, N stage, tumor size, surgery, and chemotherapy are key factors affecting AYA's survival, emphasizing the potential of surgery and chemotherapy to further enhance their prognosis.