Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the ovary

Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20 (90%) samples (median 66, range 5–272 U ml⁻¹). Preoperative serum CA 125 levels did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated in seven of nine (78%) with serous tumors (median 131, range 5–272 U ml⁻¹) and in all 11 with mucinous tumors (median 62, range 41–157 U ml⁻¹). There was no significant difference in the CA 125 levels between these two histologic types. Postoperative serum CA 125 levels, measured 3–6 weeks after primary laparotomy, were significantly lower than the preoperative ones ( P < 0.001). No difference in the postoperative CA 125 levels was found between those with and those without residual disease after surgery. Postoperative serum CA 125 levels were elevated in eight of 60 (13%) without residual tumor. None of these had relapsed at the time of analysis (26–87 months after surgery). Serum CA 125 levels tended to correlate with disease evolution during chemotherapy. Two with disease remissions had falling levels, one with stable disease had falling level and one with disease progression had rising level. Serum CA 125 samples were obtained before second-look laparotomy in seven patients. Two with negative findings at second-look had normal levels. Of five with positive findings at laparotomy only two had elevated serum CA 125 levels. Disease relapse was associated with elevated serum CA 125 levels in only one of six patients.     

What should be the cut-off level of serum CA125 to evaluate the disease status before second-look laparotomy in epithelial ovarian carcinoma?

To assess the predictive value of serum CA125 level prior to second-look laparotomy in epithelial ovarian carcinoma, 45 patients who were clinically or radiologically tumor-free prior to a second-look laparotomy were studied. Serum CA125 levels were measured 10 days prior to the operation, and were compared with the surgico-pathological results. Twenty-eight (62%) patients were found to have tumor at surgery. The serum CA125 levels were  35 U ml⁻¹ (42%) patients. Tumors were found in 14 (74%) of these 19 patients. Although a serum CA125 level  35 U ml⁻¹ was a strong predictor of the presence of an intraperitoneal tumor, a level <35 U ml⁻¹ was not predictive of a tumor-free state. When the cut-off level was accepted as 20 U ml⁻¹, 28 patients (62%) were found to have elevated CA125 level. The sensitivity, the specificity, the positive and negative predictive value and the false negative ratio were calculated as 79%, 65%, 79%, 65% and 21% respectively. The threshold value for a raised CA125 level was considered and a lower level of 20 U ml⁻¹ was suggested as a cut-off level prior to second-look laparotomy in evaluating patients with known epithelial ovarian cancer.     

Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study

The present retrospective study assessed the prognostic value of serum CA125 assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the time of relapse, serum CA125 levels ranged from 7 to 7000 U ml⁻¹. The 25%, 50% and 75% quantiles of CA125 levels were 76, 178 and 339 U ml⁻¹, respectively. Antigen values were >35 U ml⁻¹ in 67 (91.8%) of the 73 patients. Median time to recurrence was 16 months (range, 4–62 months). Serum CA125 levels at relapse were not related to site of recurrence, time to recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. Sixty patients received salvage chemotherapy at relapse. In these patients survival after recurrence was significantly related to time to recurrence ( 6 months vs < 6 months, P  = 0.0371; 12 months vs >12 months, P  = 0.0014; 16 months vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off value for the antigen: 35, 76, 178 and 339 U ml⁻¹ ), site of recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. In conclusion, time to recurrence was the only variable predictive of further survival in patients undergoing salvage chemotherapy for recurrent ovarian cancer, whereas serum CA125 level at relapse had no prognostic relevance.     

Preoperative discrimination between ovarian carcinoma, non-ovarian gynecological malignancy and benign adnexal masses using serum levels of CA125 and the polymorphic epithelial mucin antigens CASA, OSA and MSA

Serum levels of the tumor associated antigens CA125, CASA, OSA and MSA were determined preoperatively in a non-consecutive series of patients with: invasive epithelial ovarian cancer (OC, n = 87), ovarian tumors of low malignant potential (LMP, n = 9), benign adnexal masses (BAM, n = 48) and other peritoneal and pelvic malignancies ( n = 48). In addition, serum levels of CASA, OSA, and MSA were determined in 3477 asymptomatic well women. Ninety-eight percent of the asymptomatic women had CASA levels < 6.0 U ml⁻¹, OSA levels < 5.5 U ml⁻¹ and MSA levels < 80.0 U ml⁻¹. Serum CA125 levels were> 35 U ml⁻¹ in 89% of OC, in 44% of LMP, and in 23% of BAM. Serum CASA levels were> 6.0 U ml⁻¹ in 58% of OC, in 0% of LMP, and in 0% of BAM. Serum OSA levels were> 5.5 U ml⁻¹ in 61% of OC in 0% of LMP and in 4% of BAM. Serum MSA levels were> 80.0 U ml⁻¹ in 56% of OC, in 11% of LMP, and in 10% of BAM. When cut-off levels were set to exclude all patients with BAM, the best discrimination from OC using a single assay was achieved using CASA (58%). However, a combination of CASA and CA125 gave positive levels in 69% of OC at levels which precluded BAM. All markers were also elevated in some colon cancers, cervical cancers, uterine cancers and other peritoneal malignancies. A combination of CA125 and CASA levels, obtained preoperatively may assist the general gynecologist in avoiding potentially difficult oncologic surgery.     

An assessment of peritoneal lavage fluid CA125 as a tumor marker in epithelial ovarian cancer

Abstract. Redman CWE, Blackledge G, Luesley DM, Lawton FG, Kelly K, Chan KK. An assessment of peritoneal lavage fluid CA125 as a tumor marker in epithelial ovarian cancer, Int J Gynecol Cancer 1991; 1: 215–222.
CA125 levels in peritoneal lavage fluid (PLF) has been evaluated as a tumor marker in EOC. PLF samples were obtained by performing peritoneal lavage with 1L 0.9% saline, usually via temporary percutaneous cannulae. The study group comprised 87 EOC and 40 control patients; in controls, peritoneal lavage was performed at laparoscopy. Repeated access was associated with significant problems which curtails the potential of IP monitoring. Overall 25% of peritoneal lavage attempts were unsuccessful. A normal upper limit of 60 U ml⁻¹ was established for PLF CA125. In patients with postoperative disease, pre-treatment PLF and serum CA125 (using a cut-off point of 30 U ml⁻¹) levels were elevated in 66 and 87% of cases, respectively. PLF CA125 had a stronger association with the presence of ascites than with the amount of residual disease. PLF CA125 levels correlated with observed response in 71% of 51 patients with evaluable response, which was not significantly less than the 83% observed for serum CA125. Serial measurement demonstrated that rising PLF CA125 levels can predict relapse but that serum CA125 was at least as good in this respect. PLF CA125 is not a more sensitive tumor marker than its serum counterpart and will contribute little to the management of EOC.     

CA125 expression at clinical diagnosis by ovarian carcinoma not detected through antecedent serum CA125 screening

At the time of clinical presentation with ovarian carcinoma, 85% of women have an elevated serum level of the CA125 antigen, but the duration of the preclinical phase of expression of CA125 is unknown. From the database of The Royal London Hospital ovarian cancer screening project, 19 women were identified who had a serum CA125 level <30 IU ml⁻¹, measured between 2 and 24 months prior to their clinical diagnosis of ovarian cancer. Histological sections of tumor removed from these women were reviewed. In 17 cases tumor tissue was immunocytochemically stained for CA125 expression. Tumor blocks of 40 women presenting clinically with ovarian cancer with known preoperative CA125 levels were also stained for CA125 expression. The serum CA125 level at the time of diagnosis was available in six of the 19 screening study cases, four of which had levels> 30 IU ml⁻¹. In five of the 13 cases with unknown serum CA125 levels, ovarian tumor tissue expressed CA125. Among the 40 controls, 24 tumors expressed CA125 and all 24 had a serum level greater than 47 IU ml⁻¹. An annual screening test using serum levels of CA125 at a cut-off of 30 IU ml⁻¹, cannot detect all cases of ovarian cancer that express the antigen at the time of clinical diagnosis. The development of a panel of complementary tumor markers will be necessary to provide a test with a higher sensitivity for the detection of preclinical ovarian cancer.     

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 in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence

Summary. Pre-operative serum CA 125 levels were elevated (>35U/ ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (< 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1–17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of < 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.     

CA 125 measurements in ovarian cancer patients during their first postoperative week

Cancer antigen 125 (CA 125) was measured in 17 patients with ovarian carcinoma before their primary operation and during the first week after surgery. The purpose was to correlate the change in the antigen level with the patient's survival. Before surgery normal (16–30 U ml⁻¹ CA 125 values were measured in four patients and 13 had increased (75–11.356 U ml⁻¹) antigen concentrations. After surgery the marker increased to 104–931% of the preoperative level in five patients. In 12 patients the post-operative antigen level decreased to 20–96% of the preoperative level. In seven of these patients CA 125 increased without exceeding the preoperative level, after the initial postoperative fall. Thus, the CA 125 level during the first week after primary operation of ovarian cancer patients seems to be influenced by other variable factors besides a reduced amount of tumor tissue. Therefore, an investigation of the correlation between the change in the CA 125 concentration within the first week after surgery and the survival of the patient cannot be performed for the time being.     

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.     

Monitoring patients with ovarian carcinoma: the relationship of serum CA125 levels to CT scanning

Abstract. The serial levels of the serum tumor marker CA125 were compared with the results of concurrent abdominopelvic CT scans throughout the clinical course of 65 patients undergoing treatment for advanced epithelial ovarian carcinoma at this institution. Twenty-three of these patients subsequently underwent a second laparotomy following chemotherapy, and the pathological findings were correlated with the preoperative results of both the serum CA125 levels and CT scan appearances in order to establish the relative accuracies of the two tests in the diagnosis of residual disease. Initially, all patients had an elevated CA125 level (< 400 units ml^-1) which fell to normal following treatment in all cases. Seventy-five percent of patients showed continuing evidence of disease on CT grounds when both clinical examination and serum CA125 levels had normalized during or following treatment. Patients whose maximum response was PR on CT criteria relapsed faster than those achieving CR, showing CT to be a useful indicator of residual disease when the CA125 level has normalized after chemotherapy. Comparing the CT results and CA125 levels after second-look surgery in 23 patients showed CT to have a sensitivity of 85% and specificity of 42%; CA125 had a sensitivity of 50% with a specificity of 100%. Using this data, a protocol for monitoring patients undergoing treatment and follow-up for ovarian carcinoma is suggested.     

CA 125 in serum and tumor from patients with uterine sarcoma

Serial serum samples of 33 patients with primary sarcoma of the uterus were analyzed for CA 125 and frozen tissue sections of tumor from 23 patients were tested for this antigen. Before treatment, 12 of 30 evaluable patients showed serum CA 125 levels> 16 Uml⁻¹ (40%). There was no relationship between serum CA 125 level and the histologic subtype. Patients with serum CA 125> 16 Uml⁻¹ showed extrauterine tumor sites in 67% of the cases versus 33% in patients with normal CA 125 determinations ( P = 0.026). In (FIGO) stages I and II, elevated serum CA 125 levels prior to surgery were associated with a poor prognosis ( P = 0.043). Patients with recurrent or progressive disease demonstrated serum CA 125 levels> 16 Uml⁻¹ in 14 of the 20 cases (70%). Sarcoma cells were completely negative for CA 125, whereas positivity was observed in the epithelial component of mixed Müllerian tumors. The source of the elevated serum CA 125 levels in patients with uterine sarcoma may be stimulated mesothelial cells.     

The effect of abdominal surgery on the serum concentration of the tumour-associated antigen CA 125

Summary. The CA 125 assay is used to monitor the course of disease in women with adenocarcinoma of the genital tract. We measured serum CA 125 levels longitudinally in three different groups of patients who had normal scrum CA 125 levels (16 U/ml) before extensive intraperitoneal abdominal surgery (group 1, second-look laparotomy in 28 women with ovarian cancer; group 2, radical hysterectomy in 42 patients with cervical cancer; group 3,13 men and one woman who had aortic surgery for atherosclerotic occlusive disease or aneurysm formation). Following surgery, rising serum CA 125 levels were observed in 69 out of the 84 patients (82%), irrespective of the primary diagnosis, type of operation or sex. The highest levels were found during the second week after the operation (range 3–336 U/ml) and decreased gradually thereafter, to become normal at 8 weeks after surgery. It was concluded that abdominal surgery interferes with the specificity of CA 125 as a tumour marker during the early postoperative period.     

Serum CA 125 levels in epithelial ovarian cancer: relation with findings at second-look operations and their role in the detection of tumour recurrence

Pre-operative serum CA 125 levels were elevated (greater than 35 U/ml) in 44 of 46 (96%) patients with epithelial ovarian cancer. Their serum CA 125 levels ranged from 36 to 8670 U/ml and a correlation with tumour stage was found. Also, during progressive disease, 49 of 53 patients showed elevated levels. At the time of second-look operations, elevated serum CA 125 levels indicated the presence of tumour. However, the presence of small tumour residues (less than 2 cm) and of microscopically detectable tumour in biopsies were not associated with raised CA 125 levels, only a few patients (2 of 13 and 2 of 17, respectively) showed levels higher than 35 U/ml before the second-look operation. Rising levels preceded the clinical discovery of a relapse in 15 of the 22 patients with a median lead time of 3.5 months (1-17 months), and in three patients rising levels were found at the time the tumour recurrence was detected. It is concluded that CA 125, despite its general usefulness, is unable to detect tumour nodules of less than 2 cm in size, but it proved to be a sensitive and early indicator of tumour recurrence and progression.     

Serum levels of CA 125 and histological findings at second-look laparotomy in ovarian carcinoma

In a prospective study, the serum levels of CA 125 were estimated at regular intervals in 139 patients with ovarian carcinoma. Seventy-two of 78 patients with a second-look laparotomy had elevated CA 125 levels initially. The main aim of our investigation was the correlation of CA 125 levels with the histological findings at second-look laparotomy. A total of 26 patients were free from tumor. In each case CA 125 lay within the normal range. From the 46 patients where residual tumor was found, CA 125 levels were elevated in 23 cases, so that in 23 women with residual tumor, false negative levels were found. There were no false positive CA 125 levels. In all women with raised tumor marker levels at the time of the second-look laparotomy, tumor was found despite the often negative clinical or technical preoperative screening. A negative tumor marker at the time of the second look does not exclude residual tumor. For histological proof of complete remission, a second-look operation is imperative. If the CA 125 level is raised, the relevance of the planned second-look laparotomy is open to discussion.     

The effect of abdominal surgery on the serum concentration of the tumour-associated antigen CA 125

The CA 125 assay is used to monitor the course of disease in women with adenocarcinoma of the genital tract. We measured serum CA 125 levels longitudinally in three different groups of patients who had normal serum CA 125 levels (less than or equal to 16 U/ml) before extensive intraperitoneal abdominal surgery (group 1, second-look laparotomy in 28 women with ovarian cancer; group 2, radical hysterectomy in 42 patients with cervical cancer; group 3, 13 men and one woman who had aortic surgery for atherosclerotic occlusive disease or aneurysm formation). Following surgery, rising serum CA 125 levels were observed in 69 out of the 84 patients (82%), irrespective of the primary diagnosis, type of operation or sex. The highest levels were found during the second week after the operation (range 3-336 U/ml) and decreased gradually thereafter, to become normal at 8 weeks after surgery. It was concluded that abdominal surgery interferes with the specificity of CA 125 as a tumour marker during the early postoperative period.     

The prognostic implications of low serum CA 125 levels prior to the second-look operation for stage III and IV epithelial ovarian cancer.

Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml.     

CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers

Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers.     

Serum CA 125 in acute pelvic inflammatory disease

Summary. Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15–3, AFP or β₂-micro-globulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.     

Serial measurement of CA 125 in patients with primary carcinoma of the fallopian tube

Serial assay of serum CA 125 was carried out in five patients with advanced primary carcinoma of the fallopian tube. Pretreatmental levels of these patients were elevated, ranging from 145 to 535 U/ml (305 +/- 140.1, mean +/- SD). All patients showed rapid decreases in response to treatment; however, reelevations were noted in two patients concomitant with recurrence. In the remaining three patients, who are alive with no evidence of recurrence at 52, 29, and 21 months, serum CA 125 levels remained below 5 U/ml after remission. These results suggest that CA 125 is useful in monitoring patients with primary carcinoma of the fallopian tube.