Bone metastases frequently happen in solid tumors, and are related to SREs which are associated with poor prognosis and an impaired quality of life. To help patients make appropriate decisions about their treatment alternatives, it is essential to understand the incidence and prognosis of bone metastases even when combined with visceral metastasis. In this study, we analyzed the recent data from the SEER database on the incidence proportion and prognosis of patients with bone metastases secondary to 12 specific common solid tumors at the initial diagnosis. At the same time, we compared the risk of mortality and the survival time in three stages of tumors to explore the effect of bone metastasis on tumors. The data in this study could be applied broadly and influence screening paradigms for bone metastases to guide treatment, design clinical trials and counsel specific subsets of patients with cancer.
This study has several limitations. First, bone metastases in our study were identified at initial cancer diagnosis. The SEER database does not provide information on the progress of cancer, so we were unable to identify patients who developed bone metastases following the initial diagnosis. Second, routine screening for bone metastases is recommended in case there are signs or symptoms in some tumors. Therefore, some early stage asymptomatic patients were missed diagnoses resulting in an underestimation of the actual incidence of bone metastases. Third, we do not know the location, size and number of bone metastases. Additional bone metastases would increase more the risk of mortality compared with single bone metastasis which may influence the survival estimate. Similarly, we also offer data about the proportion of SREs in patients with bone metastases. Some studies have demonstrated that SREs are one of the predominant factors in unfavorable prognoses.
Although there are the abovementioned limitations, our results provide a large-scale epidemiological analysis of bone metastases because the SEER program encompasses 28% of the United States. The skeletal system is one of the most frequently mentioned metastatic sites in advanced cancer. Bisphosphonates are recommended for the prevention of SREs. However, some research has found that only a few patients with bone metastases undergo treatment of bisphosphonates [22, 23]. Early screening, prevention and treatment are important in the process of management. With the use of PET and CT, Michael et al found a higher incidence of bone metastases in lung cancer patients, ranging between 20–40% compared to 7–20% before the 20th century and 40–80% of these cases were detected at the time of the initial period. In addition, multiple bone metastases are present in approximately 80% of cases, far more than single bone metastases [24, 25]. The most frequent site of bone metastasis was the spine, followed by the pelvis and long bones . Our findings are consistent with those of previous studies showing that bone metastases from the lung, breast and prostate are the most common and account for 68% of all metastatic bone diseases [1, 2]. Prostate cancer has the highest 5-year cumulative incidence of bone metastases (24.5%), followed by lung (12.4%) renal (8.4%) and breast cancer (6.0%) whose 5-year cumulative incidence is higher than 5% in their research. A population study in Denmark showed that the incidence of bone metastases in prostate cancer was only 3% at initial prostate cancer diagnosis based on the Danish National Patient Registry ; similarly, this figure is 4.39% at the initial diagnosis in our study. For bone metastases, different primary tumors have different risk factors. The incidence of bone metastases in lung cancer reported by Gustavo et al and Katrin et al depended on the histological subtype [22, 23]. For breast cancer, it has been demonstrated that patient age, hormone receptor status, human epidermal growth factor receptor 2 and tumor size contribute to bone metastases [28, 29]. Ruatta et al reviewed and analyzed renal cancer patients in their clinics and found that approximately 4% of patients had bone metastases at the time of initial diagnosis, while approximately 13% of patients had metastases during follow-up . Compared with other primary tumors in urinary cancer, bladder cancer has a lower incidence of bone metastases in our research. Several studies have documented that the incidence of bone metastases in gastrointestinal tumors ranges from 3–7% in the course of disease [17, 31]. In most retrospective reports, only the incidence of bone metastases was considered and the period in which it occurred was not indicated. Therefore, this may be one of the reasons for the difference in incidence in some studies. In addition, the proportion of patients with bone metastases may be underestimated in the public registered database because of the proportion of asymptomatic metastatic patients. Overall, our study results are consistent with the epidemiology of bone metastases in common solid tumors and patient survival depends on the type of primary tumor.
Metastasis is one of the main reasons leading to mortality, especially the metastasis of vital organs. A study in Norway revealed that for all solid tumors, 66.7% of cancer deaths are caused by metastases . Bone, as a supporting structure, plays a critical role in movement and is also the main site of hematopoiesis. How much damage regarding survival and prognosis can bone metastases cause to patients? Bone metastases tend to reduce survival, which depends on the type of primary tumor and the presence of other visceral metastases. Patients with bone metastatic breast and prostate cancer have relatively better survival than those with lung cancer [24, 33, 34]. Patients with bone metastases exhibited better survival than those with other single site metastases, and synchronous other site metastases further impaired the survival in patient with breast and prostate cancer. Conversely, in other tumors, such as lung cancer and colorectal cancer, patients have poor survival [35, 36]. Bone metastasis as the only metastatic site reduces the 2-year overall survival from 35.5–15.8% in urothelial carcinoma . In the research, the authors think that patients with bone metastases are less likely to receive systematic therapy than other metastases because of the lower Performance Status (PS) score which may be one of the reasons for their worse survival. In our study, patients with bone metastases secondary to thyroid carcinoma had the longest survival time, especially young patients. Through comprehensive treatment, their 5-year survival rate reached 69%, which was significantly higher than that of patients treated with I131 alone . We found that patients with thyroid cancer with only bone metastases had a better prognosis than patients with local progression whose tumor invaded the prevertebral fascia or encased the carotid artery or mediastinal vessels(T4b). Like other tumors, the prognosis of these patients becomes worse when there are other sites of metastases. We also presented the number of patients with only bone metastases and contemporaneous extraosseous metastases in different tumors to offer some effective clues for the metastasis screening of cancer patients. Patients often suffer from a tumor with multiple metastases and clinicians need to be alert as to whether there are other metastases in patients with bone metastases.