Treatment of Liver Metastases in Patients with Epithelial Ovarian Cancer
Liver metastases (LM) are a significant concern in the management of epithelial ovarian cancer (EOC), as the liver is one of the most vulnerable organs for metastatic tumors. Metastatic liver tumors are approximately 18 to 40 times more common than primary liver tumors. In China, there are around 50,000 new cases of ovarian cancer annually, with a mortality rate of about 40%. The treatment of LM in malignant tumors includes both surgical and non-surgical approaches. Non-surgical treatments primarily involve systemic chemotherapy, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE).
This study retrospectively analyzed the curative effect and prognosis of liver metastases in 43 patients with EOC treated at Peking University People’s Hospital between January 2013 and July 2018. All patients were followed up until June 2019 or until they were lost to follow-up. The medical ethics committee of Peking University People’s Hospital approved this retrospective study (No. 2019-105).
Oligometastasis was defined as having five or fewer liver metastases, while nonoligometastasis was defined as having more than five liver metastases. Liver metastases found at the time of diagnosis of the primary tumor or before diagnosis were classified as simultaneous LMs, while those found after surgery were classified as metachronous metastases.
Data analysis was performed using IBM SPSS Statistics, version 22.0. The Kaplan-Meier method was used to calculate the survival curve, and univariate analysis was performed. Cox regression analysis was conducted on the statistically significant factors identified in the univariate analysis to determine the independent prognostic factors of overall survival (OS). A P-value of less than 0.05 was considered statistically significant.
The general clinical data of the 43 patients are summarized in Table 1. The median age of the patients was 54 years. Three patients had liver metastases in the left lobe, 35 in the right lobe, and five had bilobular involvement. The average diameter of the metastases was 2.7 ± 1.2 cm, ranging from 1.0 to 5.3 cm.
Among the 17 patients with simultaneous liver metastases, 14 underwent local resection (82.4%), and the remaining three received RFA (17.6%). Among the 26 patients with metachronous liver metastases, 13 underwent hepatectomy (50.0%), 11 received RFA (42.3%), and the remaining two underwent TACE (7.7%).
The median progression-free survival was 11 months, the 5-year OS rate was 36.5%, and the median OS time was 24.6 months. There was a significant difference in survival between the oligometastasis and nonoligometastasis groups (P = 0.033). The maximum diameter of metastasis was 3 cm, and the survival difference between the two groups was statistically significant (P = 0.038). There was also a statistically significant difference in survival among the three treatment methods (hepatectomy, RFA, and TACE), with OS times of 28.6, 19.3, and 9.5 months, respectively (P = 0.026). No significant differences were observed in age, pathological type, time of metastasis diagnosis, or the location of metastasis.
Five patients underwent BRCA testing, including three who received hepatectomy (two with BRCA mutations) and two who underwent RFA (one with a BRCA mutation). The OS times for these patients were 29.4 and 23.4 months, respectively. However, statistical analysis was not performed due to the small number of cases.
The univariate analysis of prognosis showed statistically significant differences in OS based on the size of residual lesions, tumor grade, number of liver metastases, maximum diameter of liver metastases, and treatment procedure. In the multifactor analysis, the size of residual lesions, which represented a combination of the number and diameter of liver metastases, was excluded. Cox regression analysis revealed that having more than five liver metastases, a maximum diameter of liver metastasis greater than 3 cm, and the treatment procedure were independent factors affecting prognosis.
Approximately 75% of EOC cases are diagnosed at an advanced stage, with 12% to 33% diagnosed at stage IV. Therefore, early diagnosis and standardized treatment are crucial in the management of liver metastases in EOC. Hepatectomy has been reported to result in the longest survival among all treatment methods. Some scholars have adopted the definition of oligometastasis, suggesting that more than five metastases should be considered unresectable. In this study, 40 patients had oligometastasis, with 27 receiving surgical resection and 13 receiving RFA. The OS of patients who underwent surgical resection was higher than that of those who received RFA (28.6 months vs. 19.3 months).
For patients with advanced EOC, optimal cytoreduction is a key factor affecting prognosis. The prognosis of recurrent EOC depends mainly on the location, size, and chemosensitivity of the recurrent tumor. Achieving optimal cytoreduction for relatively isolated and resectable tumors can significantly improve patient prognosis. In this study, 27 patients underwent optimal cytoreduction, including hepatectomy, with an OS time of 25.5 months, compared to 13.4 months in patients who received suboptimal cytoreduction. This result suggests that hepatectomy with optimal cytoreduction can prolong overall survival and improve the prognosis of patients with liver metastases from EOC.
Patients with unresectable liver metastases typically receive non-surgical treatments, including systemic chemotherapy, RFA, and TACE. RFA is often used as an effective supplement for patients with liver metastases. TACE is another minimally invasive treatment option. A study by Vogl reported the curative effect and survival rate of 65 ovarian cancer patients with unresectable liver metastases treated with TACE, with median and average survival times of 14 and 18.5 months, respectively. The 1-year survival rate was 58%, and the 2-year survival rate was 19%. In this study, the OS times for patients who received RFA and TACE were 19.3 and 9.5 months, respectively. Compared to the resectable group, the OS of the unresectable group who received non-surgical treatment was significantly shorter.
After conversion treatment, potentially resectable liver metastases can be transformed into resectable lesions. It has been reported that after TACE combined with systemic chemotherapy, the response rate to metastasis can reach 74% to 92%, and the conversion resection rate can reach 25% to 47%. In this study, two patients underwent liver resection after RFA, with OS times of 19 and 23 months.
Based on this study and a review of the literature, a treatment protocol for patients with liver metastases from EOC was established. Patients were divided into three groups: (1) the resectable group, where the metastatic tumor can be completely resected via R0 resection, with the goal of completely removing the tumor; (2) the potentially resectable group, where the metastasis cannot be initially removed but, after conversion treatment (e.g., systemic chemotherapy, RFA, and TACE), R0 resection can be performed, with the goal of minimizing the tumor and creating opportunities for surgery; and (3) the unresectable group, where liver metastases cannot be completely removed, the tumor may progress rapidly and cause symptoms, with the goal of reducing the tumor as much as possible or at least controlling disease progression.
In summary, for resectable liver metastases, surgical resection significantly improves overall survival. Non-surgical treatments have a certain effect on liver metastases from EOC, particularly for unresectable lesions or patients, and can be used as relatively conservative palliative treatments. For some patients with potentially resectable metastases, prognosis can be improved through conversion treatment, transforming them into resectable lesions.
However, this study has some limitations. Firstly, it was designed retrospectively, which may introduce treatment bias. Secondly, only a few patients were tested for BRCA mutations, an important factor affecting prognosis. Finally, the number of patients who received TACE was too small to fully explain the limitations of this treatment. Therefore, the established treatment protocol for liver metastases from EOC still requires further study.
doi.org/10.1097/CM9.0000000000001332
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