Background
Epithelial ovarian cancer is a deadly malignant disease [
1]. According to the SEER cancer statistics review (1975–2015), with more than twenty-thousand cases and fourteen-thousand deaths annually [
2]. Although with the continuous advancement of surgical techniques and the improvement of chemotherapy drugs, the overall survival rate of patients with epithelial ovarian cancer has improved in the past 50 years, but the five-year overall survival rate is still less than 50% [
3‐
5]. Numerous studies have investigated the association among potential survival trajectories as to prognosis of ovarian cancer [
6]. However, the predictors of long-term survival are not well elucidated.
Sites-distant metastases seem to represent a significant cause of morbidity and mortality among patients with epithelial ovarian cancer [
7‐
9]. Previous studies from case report and single institution experiences have yielded various conclusions, especially robust population-based estimation relating to the incidence of sites-distant metastases at diagnosis are common. However, populations-level estimation for prognosis among patients with newly diagnosed epithelial ovarian cancer and sites-distant metastases are also lacking.
In autopsy studies, patients with epithelial ovarian cancer are inclined to liver, lung, bone and/or brain metastases, not all of which are clinically apparent prior to death [
9‐
11]. Thus, in patients with both localized and/or organ specific distant metastases, the risk of prognostic factors should be reassessment. Furthermore, patients diagnosed to have localized and/or distant metastases are suitable candidates for studies on postoperative adjuvant treatment, also which can help surgeons choose appropriate surgical measures for patients in advance.
Based on a lack of proven benefit, the purpose of this study was to use the SEER database to summarize the incidence proportion of organ specific distant metastases. Based on a nomogram score, we also sought to predict survival time, in which depend on independent risk factors that contribute to prognosis.
Discussion
Epithelial ovarian cancer is the most common pathological type in ovarian malignant tumors [
5]. Based on the SEER cancer registry data analysis, the potential factors of long-term survival were comprehensively understood in this study. Taken the 5-year overall survival as a cut-off point, we observed that site of metastases and organ-specific metastases strongly were associated with overall survival in the all-cause mortality cohort and cancer-specific mortality cohort, these survival trajectories potentially contributed to patients prognosis with distant metastases, especially among patients with organ-specific metastases at diagnosis. Likewise, consistent with previous studies, other survival trajectories such as race, ovarian involvement, histology, age (taken menopause age as borderline), insurance and marital status, which were commonly relevant to the long-term prognosis [
14‐
16]. In addition, this study explored the risk of 5-year overall survival among patients with localized, regional and distant metastases, our data demonstrated that distant metastases were significantly associated with long-term survival (> 5 years). Collectively, tumor migration may contribute to the worse long-term survival in patients with site-distant metastases at initial diagnosis. To the best of our knowledge, this is the largest population-based study exploring prognosis in patients with epithelial ovarian cancer diagnosed with tumor metastases at diagnosis.
Our study reported the incidence and median survival time of different organ-specific metastases. Consistent with some but not all prior studies [
8,
11,
17], liver metastasis showed the highest incidence in all-cause mortality cohorts, followed by lung metastasis, bone metastasis and brain metastasis had relatively low incidence.
However, in solitary organ metastasis, the incidence of brain and lung metastases were relatively high. In the cancer-specific death cohort, we found that the same rules followed, except that the incidence of solitary lung metastasis and liver metastasis were higher than the former cohort. Interestingly, despite the high incidence of lung and liver metastases, the median survival time for these patients was relatively longer. Up to now, there is no standard treatment plan for distant metastasis. The main treatment is to control the primary disease. The choice of treatment plan needs to fully evaluate the patient’s condition [
18,
19]. In general, although the incidence of organ-specific metastasis is not high in the entire cohort, which have potential impact on the prognosis of patients, so attention should be paid to the decision of the treatment plan for patients with distant metastases at the initial diagnosis.
In previous studies, the prognostic assessment of patients with epithelial ovarian cancer usually used postoperative FIGO staging, pathological tissue typing, and lymphatic metastasis as evaluation criteria [
20‐
22]. Zou et al. reported that UBE2T could serve as a new prognostic marker and therapeutic target for this disease [
23]. However, with the optimization and improvement of treatment methods, more and more patients already have site-distant metastases at initial diagnosis, so it is necessary to adequately evaluate the prognosis of patients by combining the risk of different site-distant metastases. Our study found that organ metastasis had a significant impact on the 5-year overall survival, especially lung, liver and bone metastases, consistent with previous reports [
18,
24,
25].
Compared with lymphatic metastasis, patients with organ metastases have a relatively lower 5-year overall survival and worse prognosis. Therefore, our study adopted the nomogram scoring standard to quantify the metastasis of different organs, and assign points based on the specific location of the metastasis at the initial diagnosis of the patient, so as to effectively evaluate the 3-year overall survival time and 5-year overall survival time. In the process of establishing the nomogram, we used regression analysis to screen out 14 variables significantly related to prognosis. The model was robust through 1000 consecutive iteration tests. At the same time, the calibration curve also showed that the predicted value and the actual consistency.
The use of the nomogram score in estimating the risk of a patient harboring organ-specific metastases to direct clinical treatment and prognosis assessment is a novel concept. Because there are many factors affecting the prognosis of patients, the risk of metastases is worth considering. Other factors such as age, race, surgery, pathological type, FIGO staging system, insurance, and marital status also should be considered. In short, we have established a visual prognostic evaluation model, as well as beneficial reference value for guiding patients’ treatment and prognosis.
Our research also has the following limitations. First, we use the SEER database to assess the prognostic risk of patients. To the best of our knowledge, tumor metastases that affect the prognosis of patients should also consider many factors such as retroperitoneal lymph nodes and chemotherapy. This information cannot be obtained from the database. Second, there are some patients who may be at risk of distant metastases during treatment. We cannot accurately obtain detailed information about these patients, so the risk of recurrence cannot be assessed. Third, laboratory indicators such as CA125 are related to the prognosis of ovarian cancer patients, but the database has only partial records, so it was not included in this study. Finally, we cannot obtain a detailed treatment plan for the patient, so we cannot assess the potential influencing factors of the prognosis assessment.
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