The outcome and prognosis of 147 patients with surgically confirmed ovarian metastases from extragenital primary cancer in our series reflected the complexity and challenges for the management of this specific population. 12 patients with initial preoperative diagnosis of primary ovarian cancer turned out to have ovarian metastases from gastrointestinal tract or breast cancer. The prognosis of ovarian metastases is dismal and the benefit of ovarian metastatectomy remained to be elucidated.
The mechanism of ovarian metastasis has largely been discussed in the literatures. Besides the commonly described routes of metastases for metastastic ovarian tumors arising from extragenital primary cancer that include direct invasion, surface implantation, other possible route for gastric cancer to disseminate to ovary may include lymphatic drainage via the receptaculum chili to the urogenital lymph vessel trunks, and, hematogenous spread from gastrointestinal tract tumors [8
]. The lymphatic dissemination and transcoelomic spread are also proposed to be important mechanisms due to the high incidences of synchronized involvement of peritoneum and lymph nodes in colorectal cancer [9
]. The exact mechanism of the spread of breast cancer to the ovaries had not been elucidated but the risk of primary ovarian cancer is increased in women with breast-ovarian cancer syndrome (BRCA1/2 mutation) [10
], lymphoma had been reported to spread to the ovaries but there was none in our series [4
Recent observations have reported a higher incidence of colorectal origin compared to gastric origin, and more frequently from colon rather than rectum [2
]. Similar phenomenon was observed in our study. Nearly half of our patients had primary cancer that arose from colorectal cancer, and the ratio of colon to rectum was 3:1. Radiotherapy for rectal cancer with T3/4 or positive lymph node disease may be the contributing factor as ovarian micrometastases are eradicated and ovarian blood supply is impaired, reducing the risk of ovarian spread. Colonoscopy should not be omitted in cases presenting with ovarian tumors as evident colorectal cancer-related symptoms that may include defecate change or rectal bleeding were rarely the initial presentation [14
The survival of the ovarian metastases patients from extragenital tumors is related to the primary tumor sites. In our series, patients with tumors originated from breast exhibited the best median survival time of 41 months, followed by those of colorectal and stomach, with the median survival time of 8.8 months and 7.4 months, respectively, which is comparable with previous data [16
]. This result may be partly attributable to the nature of breast cancer having a better prognosis compared to the tumor from GI tract. Differences in tumor biology among individual patients, tumor types, or even within a given tumor, may also contribute to survival. As is previously reported [12
], the median survival among patients with ovarian metastases of the gastrointestinal cancer origin was 13-30 months. The estimated 5-year disease free survival of the patients without other metastastic lesions reached 40% after complete resection [13
]. However, the survival of the patients with gastrointestinal origin in our series was disappointing, with the median OS of 8.2 months. One explanation could be due to the fact that nearly 40% of the patients had synchronous ovarian metastases, representing a patient population of poorer prognosis. Moreover, the proportion of pathological type including mucinous carcinoma and signet ring cell carcinoma was nearly 40% in this cohort, which was also an unfavorable survival factor. Another reason could be that 30% of the patients were presented with combined extensive metastases at the diagnosis, indicating worse prognosis as found in other studies [13
].. Peritoneal dissemination was reported as an adverse factor influencing the survival time [15
]. In our analysis, huge volume of ascites and high incidence of local invasion were also determined as a poor prognostic factor. Additionally, the finding that there was no survival difference based on tumor size and laterality indicates that the development of ovarian metastases is a sign of a more aggressive disease and the ovarian metastases are diagnosed late in the cancer disease process.
Therefore, whether maximal surgical debulking should be conducted was controversial. Aggressive therapeutic measures similar to the practice for primary ovarian cancer had been advocated, especially in the case of colorectal cancer with ovarian metastases which was less responsive to chemotherapy [18
]. Bilateral oophorectomy for ovarian metastasis from colorectal cancer have been shown to have a positive impact on disease-free and overall survival in isolated ovarian metastases patients in an Italian study [20
]. Also, for patients with gastric cancer, a Korean study suggested that debulking or gastrectomy plus metastasectomy may bring survival benefits for patients with distant metastases who were receiving systemic chemotherapy [21
]. However, other believed that metastatectomy should be reserved for curative intent because ovarian metastases tends to spread via a transcoelomic route and hence, a harbinger of peritoneal metastasis [9
]. It remains unclear whether prophylactic bilateral oophorectomy would improve the survival, and routine practice of prophylactic bilateral oophorectomy may not be justified as to the low frequency of isolated ovarian involvement without distant metastases [9
]. The effect of metastatectomy could not be determined in this study with its small sample size and retrospective in nature. Variability of distant metastatic status besides the ovaries and surgical procedures would bias the evaluation of surgery-related quality of life and long-term survival. In our study, it appeared that palliative surgery did not improve the long-term survival and well-designed prospective trials focusing on this aspect is needed to resolved the issue.
Effective methods have to be introduced, as traditional tumor marker in ovarian tumor, CA125, was not specific in predicting the survival of patients with ovarian metastases from extragenital cancer. PET/CT may be considered as an alternative approach in search for primary tumor sites and it was reported that a variable maximum SUV in ovarian metastases may be correlated to different primary origins [24