The level of CA125, a surface glycoprotein associated with m¨ullerian epithelial tissues, is elevated in about 80% of patients with epithelial ovarian cancers, particularly those with nonmucinous tumors (245–247). The levels frequently become undetectable after the initial surgical resection and one or two cycles of chemotherapy. Carcinoembryonic antigen (CEA) levels are often elevated in patients with ovarian cancer, and the test is too nonspecific and insensitive to be used in the management of these patients, apart from patients with a mucinous cancer of the ovary (48).
Levels of CA125 were correlated with findings at second-look operations. Elevated levels are useful in predicting the presence of disease, but negative levels are an insensitive determinant of the absence of disease. In a prospective study, the predictive value of a positive test was 100%; if the level of CA125 was elevated (>35 U/mL), disease was always detectable in patients at the second-look procedure (245). The predictive value of a negative test was only 56%; if the level was less than 35 U/mL, disease was present in 44% of the patients at the time of the second-look surgery. A literature review suggests that an elevated CA125 level predicts persistent disease at second-look surgery in 97% of the cases, but the CA125 level is not sensitive enough to exclude subclinical disease in many patients (246).
Serum CA125 levels can be used during chemotherapy to follow those patients whose levels were positive at the initiation of therapy (245). The change in level correlates with response.
Those patients with persistently elevated levels after three cycles of treatment probably have persistent disease. When levels rise after treatment, almost invariably treatment has failed, and continuation of the current regimen is futile. A retrospective study determined that a doubling of the CA125 level from its nadir in those patients with a persistently elevated level accurately predicts disease progression (247).
Radiologic tests assess response in patients with measurable lesions at the start of therapy. In patients who have no or minimal residual disease following cytoreductive surgery, the value of these tests is limited, but they may be useful in follow-up, especially to document the site of recurrence. Ascites can be readily detected, but quite large omental metastases can be missed on CT scan in patients with recurrent disease (248). If liver enzyme levels are abnormal, the liver can be evaluated with a CT scan or ultrasonography. A positive CT scan and fine-needle aspiration (FNA) cytology indicating tumor persistence could document persistent or recurrent disease, but the false-negative rate of a CT scan is about 45% (249). Positron-emission tomography (PET) alone, or with CT imaging, may help detect relapse, although the relative value of adding PET is not established. There appears to be a higher false-positive rate with PET compared with CT (106,107). MRI can be used as an alternative to CT in patients with allergies to the contrast medium (105).
Secondary cytoreduction may be defined as an attempt at cytoreductive surgery at some stage following completion of first-line chemotherapy (250–253). Patients with progressive disease on chemotherapy are not suitable candidates for secondary cytoreduction, but patients with recurrent disease are occasionally candidates for surgical excision of their disease. Tumor resection under these circumstances should be restricted to those who have a disease-free interval of at least 12, but preferably 24, months or those in whom it is expected that all macroscopic disease can be resected, regardless of the disease-free interval (250–258). Complete resection is possible when there are only one or two isolated recurrences in patients without diffuse carcinomatosis (258).