Immunoscintigraphy using CA 125 antibodies in the management of ovarian cancer

Summary Radioimmundetection (RID) using anti-CA 125 antibodies proved to be a valuable tool in the follow-up of metastasizing ovarian cancer. Sensitivity, specificity, and accuracy were high. RID had no clinical side effects. But some patients formed antibodies which interfered a) with the evaluation of the scintigram and b) with further measurement of CA 125 levels. We found 2 cm diameter metastases that were not detected by computed tomography. However, the heterogeneity of tumor metastases limits the sensitivity of this method. CA 125 serum levels, immunohistochemistry, and immunoscintigraphy did not always correlate. Monitoring serum levels of CA 125 was most valuable in clinical management of tumor spread and in the optimal use of RID.     

测定血清CA125水平在卵巢癌的临床意义

目的分析卵巢癌手术前后测定血清CA125水平的临床意义.方法采用回顾性分析方法,1994年1月～2000年8月我院收治的137例卵巢癌患者手术前后血清CA125水平结合病理、分期、分化、手术情况\治疗及预后等临床资料进行分析.结果在卵巢癌,术前血清CA125水平与病理类型及分期相关(P=0.006),术后2～4个月血清CA125水平与手术的癌细胞减灭程度相关(P=0.025),术后5～7个月血清CA125水平与是否坚持化疗相关(P=0.014),且为预测复发及生存时间的重要因素.术后血清CA125水平的升高可预测复发,其敏感性为87.5%,且通常较临床证实复发提前,平均为7.2个月.结论卵巢癌患者术前测定血清CA125水平可初步反映病理类型及分期,术后监测血清CA125水平可反映手术的肿瘤减灭程度,及时预测复发,并可判断预后.     

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.     

卵巢癌患者血清中TPS、CA125水平及其临床意义

目的 探讨卵巢癌患者血清TPS、CA125水平的临床应用价值。方法 分别检测15例卵巢良性肿瘤患者（良性对照组）和39例卵巢癌患者（卵巢癌组）初诊、治疗后以及15例卵巢癌复发患者血清TPS、CA125水平，统计结果进行比较。结果卵巢癌组血清TPS、CA125水平显著高于良性对照组（P〈0．01）；TPS对卵巢癌诊断的灵敏度和特异度为71．8％和86，7％，CA125为84．6％和86．7％，两者差异无显著性（P〉0．05）；治疗后患者血清TPS、CA125水平低于治疗前（P〈0．01、P〈0．05），而复发时TPS水平又显著高于治疗后（P〈0．05）。结论 血清TPS检测有助于卵巢癌诊断、疗效观察及预后判断，联合检测CA125可提高其临床应用价值。     

The role of cancer antigen 125 (CA 125) in the management of ovarian epithelial carcinomas

From June 1, 1984, to May 31, 1985, 98 cases of epithelial ovarian carcinomas were assessed and followed prospectively using a new murine monoclonal antibody OC 125 which detects the antigen CA 125. Serous tumors comprised 43.7% of cases, mucinous tumors 20.4%, endometrioid tumors 16%, and other epithelial tumors 19.4%. Tumors of low malignant potential and benign epithelial cystadenomas were not included. For this study the upper limit of normal for CA 125 was 20 U/ml. Thirty-six were new cases. In this group the initial CA 125 levels greater than 20 U/ml, greater than 35 U/ml, and greater than 65 U/ml were 97.2, 94.4, and 86.1%, respectively. When mucinous types were excluded the specificity rate did not change significantly. There was no significant difference in initial CA 125 levels between early stages I and II and late stages III and IV. No correlation between tumor bulk and the serum level of antigen was observed. The remaining 62 patients were being followed and in this group 50 were considered to be in remission. Six cases in the remission group had elevated CA 125 levels greater than 20 U/ml and 5 of these developed clinical recurrence. The correlation between the clinical status and concordant fluctuations in the serum levels of CA 125 in all histological types was 87.8 and 93.5% when 10 cases of mucinous tumors were excluded. The contingency coefficient was 0.746. Seven SLOs were performed. All had CA 125 levels less than 20 U/ml and the mean was 6.9 U/ml. Only 1 case was positive with microscopic disease. In our experience CA 125 was invaluable in the management and follow-up of patients with ovarian carcinoma especially for the early detection of recurrent disease and for the monitoring of patients on therapy.     

Prognostic value of CA 125 in advanced ovarian cancer

CA 125 was measured during early chemotherapy in 121 patients with FIGO stage III or IV ovarian cancer to investigate if the antigen could be used as a prognostic parameter. CA 125 was determined before the start of chemotherapy and 1 month after the first, second, and third course. The antigen level before the start of chemotherapy held no prognostic information. CA 125 was a significant prognostic parameter in all three courses but its correlation with survival improved with the number of courses. Patients with high marker levels (greater than 100 U/ml) 1 month after the third course had a median survival of 7 months. This should be compared with a 50% 5-year survival in patients who had 10 U/ml or less and a median survival of 22 months among patients with intermediate CA 125 levels. Cox regression analysis of the covariation between survival, CA 125, and five variables (age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor) showed that the CA 125 value was the most significant prognostic parameter. As a consequence of this study, chemotherapy of patients with high CA 125 levels 1 month after the third course may be discontinued and replaced by palliative therapy if other curative regimens are not available.     

Normal serum CA125 half-life and normal serum nadir CA125 level in patients with ovarian cancers

The normal serum CA125 half-life and distribution of the normal serum nadir CA125 value in patients with epithelial ovarian carcinoma (EOC) have not been determined yet. Among patients with EOC, 41 patients met the inclusion criteria of the present study: the patients that underwent complete cytoreductive surgery and six cycles of platinum-containing chemotherapy, and who had no recurrent disease more than five years. Serum CA125 half-life (T1/2) during primary surgery and primary chemotherapy was calculated and serum nadir CA125 level was evaluated by logarithmic-transformed serum CA125. Median value of nadir CA125 was 7 U/ml (range 3-20 U/ml), and the mean ln (serum nadir CA125) was 1.96 +/- 0.45. Mean T1/2 was 10.4 days in all patients, and T1/2 value was associated with the preoperative serum levels of CA125. Predicted slope of CA125 regression curve was also influenced by the preoperative CA125 value. The present study provides fundamental information with regard to normal half-life time and normal nadir of CA125 in EOC patients.     

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 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.     

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.     

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.     

Longitudinal study of CEA and CA125 in ovarian cancer

Carcinoembrionic antigen (CEA) and cancer antigen 125 (Ca125) levels were measured at regular intervals over a 24-month period in 19 patients with proven ovarian cancers. In 91.5% of the cases with recurrent or progressive disease, Ca125 levels were increased whereas only 34% of these patients had increased CEA levels. Furthermore, reduction of the tumoral mass was associated with a decrease of Ca125 levels in all patients. It is proposed that determination of Ca125 levels in ovarian cancer might provide a valuable prognostic tool for the assessment of the evolution of the disease.     

Serum CA 125 levels and survival in advanced ovarian cancer

We made a retrospective analysis of 85 patients with elevated serum CA 125 after surgery for ovarian cancer. Absolute CA 125 serum levels were a poor guide to prognosis. However, the ratio between the serum CA 125 after the first, second, or third course of treatment and the postoperative value was an excellent guide to prognosis. These were also independent and stable in the Cox Regression analysis.     

Chemotherapy-induced changes of CA 125 in patients with epithelial ovarian cancer

OBJECTIVES: CA 125 is a tumor marker widely used to diagnose, monitor, and follow-up women with epithelial ovarian cancer, as the marker is well related to the amount of vital tumor cells. However, CA 125 before the operation or during the first 2 courses of chemotherapy does not provide enough information concerning survival to serve as a prognostic marker. The present investigation was inspired by studies describing a paradoxical increase of tumor markers (CEA, CA 125, and CA 15-3) in the days after chemotherapy of women with breast cancer. If CA 125 increases within days after chemotherapy, the increase may be caused by death of the cancer cells. It was therefore speculated if a CA 125 spike may serve as an early prognostic parameter. The aim of the present investigation was to evaluate if CA 125 increases within days after the first course of chemotherapy of women with ovarian cancer. PATIENTS: Twenty women with epithelial ovarian cancer were included in the study. CA 125 was measured in each woman on day 0 (the day of, but before initiation of chemotherapy) and 1, 3, 5, 7, 9, and 14 days after chemotherapy. RESULTS: One woman was excluded due to normal CA 125 values. The remaining 19 patients displayed a significant decrease in CA 125 during the 14-day period after chemotherapy. CONCLUSION: In the present study, no chemotherapy-induced increase of CA 125 within the first 14 days after chemotherapy could be demonstrated.