Incidence of liver metastasis in ovarian cancer patients
There were 25293 ovarian cancer patients in the analyses, and 48.14%, 5.55%, 7.92%, 4.47.6%, 5.91%, 1.68%, 1.14% and 5.47% of those patients had the serous, mucinous, endometrioid, mixed, clear cell, carcinosarcoma and neuroendocrinoid types, respectively. For the cohort presented with distant organ metastases at any site (n = 2922), 44.90%, 2.49%, 2.09%. 2.19%, 1.98%, 3.42% and 1.44% had the serous, mucinous, endometrioid, mixed, clear cell, carcinosarcoma and neuroendocrinoid subsets, respectively. Of these, 1749 patients with liver metastases, showing 6.91% of the ovarian cancer population and 59.86% among the subset with metastatic disease at any site. Table 1 have detailly presented the number and incidence proportions of liver metastases in newly diagnosed ovarian cancer, and stratified by ovarian cancer histological subtypes. The frequency of liver metastasis was highest in ovarian carcinosarcoma patients (14.12% of the entire cohort). Among the subset with distant organ metastases, the proportion of those with liver involvement was approximately 60%, and liver metastasis specificity was the highest in the clear cell type (70.69% of the metastatic subset) and neuroendocrinoid carcinoma (71.43% of the metastatic subset) subtypes. For high- and low-grade serous ovarian cancer, the incidence proportion of liver metastases was significantly higher among those with high-grade serous ovarian cancer than among those with low-grade serous ovarian cancer (5.32% vs. 2.65% of the entire cohort) (Table 2). The influence of age and race is shown in Supplementary Table 1.
On multivariable logistic regression among metastatic ovarian cancer patients indicated that the serous (OR=7.94, 95% CI=4.37-14.43), mucinous (OR=3.68, 95% CI=1.88-7.18), endometrioid (OR=2.26, 95% CI=1.15-4.46), mixed (OR=4.23, 95% CI=2.15-8.32), clear cell (OR=3.45, 95% CI=1.77-6.74), carcinosarcoma (OR=17.76, 95% CI=9.26-34.09) and neuroendocrinoid (OR=13.06, 95% CI=6.47-26.36) subtypes, when compared with non-epithelial subtype. Ovarian carcinosarcomas was significantly greater odds of having liver metastases at initial diagnosis. More detail information and results are presented in Table 3.
Survival of liver metastasis in patients with ovarian cancer
The median cancer-specific survival (CSS) for non-metastatic ovarian cancer patients was 77 months, but the CSS times for those with ovarian cancer with only liver metastasis was 21 months. The CSS times were 19 months, 18 months and 11 months for those with ovarian cancer with distant organ metastasis, liver metastasis and metastasis at ≥2 sites (including the liver) (Figure 2). Among the patients with different subtypes of ovarian cancer with only liver metastasis, those with nonepithelial (38 months) and serous ovarian cancer (33 months) experienced the longest median CSS, and patients with the mucinous (5 months) and neuroendocrinoid (6 months) subtypes experienced the shortest median survival (Figure 3A). The multivariate Cox regression analysis showed that patients with different subtypes were independently prognostic factor for CSS for liver metastatic ovarian cancer (Table 4). Mucinous (vs nonepithelial subtype; hazard ratio, 0.26; 95% CI, 0.14-0.49; P<0.001) subtype was significantly associated with decreased survival. Among those with serous ovarian cancer, high-grade ovarian cancer resulted in worse survival (vs low grade; hazard ratio, 0.34; 95% CI, 0.15-0.78; P<0.001) (Figure 3B).
Surgery is an important method of treatment for ovarian cancer. We found that the use of surgery was associated with a longer survival time compared with patients without surgery for ovarian cancer with only liver metastasis at the initial diagnosis (P<0.001, Supplementary Figure 1). Interestingly, the survival time of non-metastatic ovarian cancer patients without surgery was shorter than that of ovarian cancer patients with liver metastasis who received surgery (HR=0.46, 95% CI=0.42-0.51).