Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer

Serum CA 125 levels were measured preoperatively in 100 women undergoing diagnostic laparotomy for palpable adnexal masses. All 11 patients with frankly malignant nonmucinous ovarian carcinoma had serum CA 125 levels greater than 35 U/mL and nine of the 11 had serum CA 125 levels greater than 65 U/mL. If patients with mucinous and borderline lesions were included, serum CA 125 was greater than 35 U/mL in 11 of 18 and greater than 65 U/mL in nine of 18 patients. Among 14 individuals with pelvic masses and CA 125 greater than 65 U/mL, 13 had some form of gynecologic malignancy. These results suggest that CA 125 assay can be used as a diagnostic adjunct for discriminating benign from malignant pelvic masses.     

CA125 parameters in survivors and non-survivors with epithelial ovarian cancer

Abstract. Cruickshank DJ. CA125 parameters in survivors and non-survivors with epithelial ovarian cancer. Int J Gynecol Cancer 1991; 1 : 279–284.
The relationship between different CA125 parameters and survival in patients with epithelial ovarian cancer was investigated in a prospective study. This involved 161 patients of whom 64 died and 97 remained alive. The established prognostic factors of stage and residual disease were controlled for and the population characteristics (age, follow-up/survival duration, histologic subtype, grade) were comparable in the 'dead' and 'alive' groups. For patients with stage I and II disease preoperative serum CA125, pre-chemotherapy serum CA125, plateau serum CA125 and time to reach the plateau level were all higher in the non-survivors when compared with survivors. In contrast, preoperative serum CA125 and pre-chemotherapy serum CA125 were significantly higher in survivors with stage III and IV disease. A possible explanation for these results includes the suggestion that early- and late-stage ovarian cancer may be different 'diseases' with different natural histories rather than being a continuum. Alternatively, the tumor-associated antigen CA125 being a membrane glycoprotein may have a beneficial, perhaps immunologic role in advanced disease.     

Tumour-associated antigen CA 125 in patients with ovarian cancer

The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6-30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.     

Tumour-associated antigen CA 125 in patients with ovarian cancer

Summary. The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6–30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.     

CA 125 as an independent prognostic factor for survival in patients with epithelial ovarian cancer

Serum CA 125 levels (upper normal value less than 35 U/ml) determined before surgery and 3 months after surgery were evaluated as independent prognostic factors for survival in patients with epithelial ovarian carcinomas. In 163 women preoperative serum levels of CA 125 (p = 0.13) gave no additional information with regard to the relationship of survival prognosis to histologic grade (p = 0.04) and to the diameter of residual tumor mass (p = 0.03). In 132 patients serum CA 125 levels were also determined 3 months after surgery and reflected the effectiveness of the first two cycles of postoperative cytotoxic treatment. At that time CA 125 was the strongest independent prognostic factor for survival (p = 0.0006 Cox model), as compared with histologic grade (p = 0.06), International Federation of Gynecology and Obstetrics stage (p = 0.15), and diameter of residual tumor mass (p = 0.66). Therefore, we concluded that serum CA 125 levels determined 3 months after surgery can identify a high-risk population among patients with epithelial ovarian carcinomas for whom a more aggressive or more intensive treatment might be beneficial.     

Use of CA 125 to monitor patients with ovarian epithelial carcinomas

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.     

CA 125 in the follow-up of patients with ovarian cancer

Three hundred and ninety-five CA 125 serum values of 72 patients with ovarian cancer were correlated with the clinical status. With a threshold value of 35 U/ml we found true negative values in 85% and true positive values in 93%. No correlation between preoperative CA 125 values and tumor stage was noted at primary surgery. During follow-up, 17 women had marker values between 35 and 65 U/ml. Three out of 7 women in clinical remission showed a value greater than 65 U/ml at subsequent follow-up and developed recurrent disease. In 8 patients out of 20 re-laparotomies, tumors with a maximum diameter of greater than 2 cm were confirmed with a preoperative serum CA 125 concentration greater than 65 U/ml. Two out of 3 patients with a tumor diameter less than 2 cm at re-laparotomy revealed CA 125 serum concentrations less than 35 U/ml. A false positive CA 125 value was found in one patient without demonstrable active disease. The calculated doubling time of the CA 125 values ranged between 23 and 173 days; the median value was 67 +/- 47 days. After 6.2 +/- 1.3 doubling times death ensued.     

CA 125 in the follow-up of patients with ovarian cancer

The value of CA 125 measurement in the diagnosis and follow-up of ovarian cancer was studied in 102 patients. The CA 125 levels were elevated in 88% (322/365) of samples from 82 patients with clinical evidence of disease and in 14% (56/403) of samples from 58 patients without clinical evidence. Preoperative levels were elevated in 84% (44/52) of the patients, and in 100% of those with stage III and IV disease. In patients with non-mucinous tumors the preoperative levels were elevated in 95% of cases (38/40). CA 125 levels were significantly correlated with the course of disease in 88% (36/41) of patients whose tumor regressed, and in 87% (20/23) of those whose tumor progressed. Before second-look surgery of 48 patients, the sensitivity of the CA 125 test was 35% and the specificity was 86%. The results suggest that, although far from infallible, CA 125 is a useful marker for ovarian cancer. It is useful for monitoring the course of chemotherapy, but normal levels do not rule out the possibility of persistent or recurrent disease.     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

CA 125 in monitoring chemotherapy of the patients with ovarian cancer

Changes in CA 125 antigen concentration and serum half-life were determined in 63 women with ovarian carcinoma during chemotherapy following various types of surgery. Concentration of CA 125 in serum correlated with the degree of clinical advancement of the tumor, 20.00 and 688.84 U per ml at stages I, II, and IV, respectively, and with remaining tumor mass, despite chemotherapy, serum CA 125 level rose after exploratory surgery. Estimation of CA 125 levels proved less useful in the mucinous type of ovarian carcinoma. The treatment scheme including Cisplatinum reduced CA 125 levels most effectively correlated with good clinical response to the therapy. Testing the half-life time appeared to provide a good prognostic index, 6.25 +/- 2.08 days after radical surgery and 44.87 +/- 26.5 days after probatory laparotomy.     

Serum CA 125 in epithelial ovarian cancer. A longitudinal study

Summary. Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level >35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels < 35 U/ml, whereas all the patients with no change or with a progressive disease had levels >35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (>35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.     

Potential markers that complement expression of CA125 in epithelial ovarian cancer

BACKGROUND: When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection. METHODS: From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. RESULTS: Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1. CONCLUSIONS: At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.     

CA125 kinetic parameters predict optimal cytoreduction in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy

ObjectiveTo evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS).MethodsThe present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS.ResultsOne hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97–0.99], p = 0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56–7.10] (p = 0.0008).ConclusionOur data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS.     

CA 125 regression: a model for epithelial ovarian cancer response

The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method.     

Stage- and CA125–related survival in patients with epithelial ovarian cancer treated at a cancer center

Abstract.   Board RE, Bruijns CTPH, Pronk AE, Ryder WDJ, Wilkinson PM, Welch R, Shanks JH, Connolly G, Slade RJ, Reynolds K, Kitchener HC, Jayson GC. Stage- and CA125–related survival in patients with epithelial ovarian cancer treated at a cancer center. Int J Gynecol Cancer 2006; 16(Suppl. 1): 18–24.
Current accepted prognostic indicators in ovarian cancer include performance status, surgical (FIGO) staging, and residual disease after operation. Here we present data from a prospective analysis of patients with ovarian cancer treated at the Christie Hospital. We confirm the independent prognostic effects of FIGO staging, performance status, and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance ( P = 0.02). We present survival data and show that the 3-year, cancer-specific survival for stage I disease is 90%. We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging. Further clinical trials are needed to test whether combinations of surgical, histologic, biochemical, and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required.     

CA125 in peritoneal fluid of ovarian cancer patients.

The presence of CA125 was assessed in peritoneal fluid from 70 patients with ovarian cancer and 32 control patients. The follow-up period ranged from 39 to 89 months (median, 56 months). The cutoff for normal peritoneal fluid CA125 levels was determined to be 250 U/ml. A positive correlation between the serum and peritoneal fluid CA125 levels was observed (P less than 0.001). Peritoneal fluid levels were higher than serum levels in all patients. Patients with evidence of active ovarian cancer showed higher peritoneal fluid CA125 levels than the control patients (P less than 0.001). Peritoneal fluid CA125 levels correlated inversely with survival (P = 0.004). The peritoneal fluid CA125 levels were higher in patients with bulky tumor than in those with small (less than 1 cm) tumors (P less than 0.001). Eight out of twenty-six patients with active cancer and available peritoneal cytology had a negative peritoneal cytology. Three of these patients showed elevated peritoneal fluid levels. Three patients out of twenty-four showed elevated peritoneal fluid CA125 levels at second-look laparotomy. These 3 patients had negative biopsies at second-look surgery, but relapsed during the observation period. At second-look laparotomy an elevated peritoneal fluid CA125 level may imply a bad prognosis, but a normal level does not exclude the presence of disease.     

Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer

Serum CA 125 levels and surgical findings were prospectively compared in 96 secondary laparotomies performed on patients with epithelial ovarian cancer. All patients had documentation of an elevated CA 125 level (greater than 35 U/ml) at a time when ovarian cancer was present, and thus the tumors were known to be "marker positive." Operation was performed in 45 patients who were clinically free of disease and in 51 patients in whom there was clinical evidence of disease. At the time of operation, 29 patients had normal CA 125 levels; persistent disease was documented in 18 (62%) of these. Of the patients with normal CA 125 levels at the time of operation, those with persistent disease had a significantly higher mean CA 125 level (16.9) than those with no disease detected (8.8, p = 0.001). At exploration, cancer was found in 84 patients. There was a correlation between the maximum diameter of the largest residual tumor mass and the accuracy of the CA 125 level as follows: microscopic to 1 cm disease, 55% accuracy; greater than 1 to 5 cm disease, 80% accuracy; greater than 5 cm disease, 92% accuracy (p = 0.013). There was no correlation of CA 125 accuracy with the patient's age, number of months from initial diagnosis, tumor stage, grade, or cell type, or the highest-ever level of CA 125. Of the 84 patients with tumor found at exploration, 66 had elevated CA 125 levels, yielding a sensitivity of 78.5%. There were 12 patients with no tumor found at exploration; 11 of these had normal CA 125 levels. The one patient who had an elevated CA 125 level subsequently had a recurrence; the corrected specificity is thus 100%. An elevated CA 125 level is an accurate predictor of persistent disease. Most of these patients will have gross tumor present. The accuracy of the CA 125 level in detecting disease is related to the amount of tumor present. In our population, the predictive value of an elevated CA 125 level was 100%; the predictive value of a normal CA 125 level was 38%.     

Cancer antigen CA 125 in ovarian cancer

AIM: To estimate the diagnostic and prognostic value, pathological and clinical correlation of cancer antigen 125 (CA125) in ovarian cancer (OC). Retrospective analysis was done of 350 patients who were operated for OC in years 1990-2001 in Gynecology Clinic MU of Gdansk. We analyzed those before primary operation (PO) and second look laparotomy (SLL). Chi 2 and t-Student tests were used. RESULTS: Before PO 18% OC patients had CA125 less than 35 and 43.8% more than 600 U/ml, for benign tumors it was 59.9 and 1.1 respectively (p < 0.001). 56.2% with complete remission and 43.8% with progress disease in SLL had normal values of antigen before the operation. There were 32 patients who had CA125 > 600 before SLL and all of those had progress disease. The positive and negative predictive value of CA125 before SLL were 0.94 and 0.56 respectively. Cytoreduction with no macroscopic disease was achieved in 45% of patients with CA125 < 600 U/ml before PO, and it was 19.2% for those with antigen > 600 (p = 0.001). We looked for differences of CA125 levels depending on clinical and pathological data. According to our results only histology (p = 0.02) and clinical stage (p = 0.02) influenced CA 125 levels. CONCLUSIONS: There is a good correlation between elevated levels of CA125 and state of the disease in SLL, and we consider SLL as obligatory to perform as there is a low negative predictive value of CA125. The CA125 before primary operation has prognostic significance to possibility of optimal cytoreduction.