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.     

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.     

CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients

OBJECTIVE: To evaluate immune responses and clinical outcomes for combined oregovomab and chemotherapy treatment of patients with recurrent ovarian cancer. METHODS: Patients with advanced recurrent ovarian cancer were administered oregovomab over 12 weeks before chemotherapy, then optionally concurrent with chemotherapy x 2. Antibody responses, including human anti-mouse antibody (HAMA), anti-idiotypic antibody (Ab2) and anti-CA125, were assessed by ELISA; T-cell responses to CA125, autologous tumor and oregovomab by interferon (IFN)-gamma enzyme-linked immunoSPOT (ELISPOT) were also evaluated. Clinical outcomes were recorded. RESULTS: Twenty patients were enrolled; median follow-up was 15.8 months. Oregovomab was well tolerated and did not produce drug-related serious adverse reactions. In 15/19 (79%) patients, robust treatment-emergent humoral responses were observed to the constant (HAMA) and variable region (Ab2) of oregovomab, and 2/19 (11%) patients developed anti-CA125 antibodies. Significant increases in T-cell responses were measured in 7/18 (39%) patients in response to CA125, in 5/8 (63%) patients in response to autologous tumor and in 9/18 (50%) patients in response to oregovomab. Immune responses appeared by week 12 (four doses) and were generally maintained or augmented in patients continuing combined treatment with oregovomab and chemotherapy. Median survival was 70.4 weeks (4.6-141.6 weeks), and the median progression-free interval was 11 weeks (2.6-114.6 weeks). Patients who mounted a T-cell response to CA125 and/or autologous tumor showed significantly improved survival (median not reached vs. 51.9 weeks, P = 0.002) compared to patients who did not. CONCLUSIONS: Oregovomab was well tolerated and induced multiple antigen-specific immune responses, maintained during concomitant chemotherapy. A significant survival benefit was observed in patients mounting a T-cell response to CA125 and/or autologous tumor.     

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.     

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.     

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.     

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.     

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.     

Value of CA 125 as a marker of ovarian cancer.

Elevated CA 125 level was noted in 0.2-5.9% healthy women, 2.2-27.8% patients with benign ovarian cysts, and approximately 80% patients with nonmucinous ovarian cancer. In the early stages of cancer, CA 125 level was lower than in the disseminated process (with tendency to higher levels in cases of accompanying exudates to body cavities). The level was found to correlate with the mass of tumor, extent of surgery and response to chemotherapy. Maintenance or increase in CA 125 level after three months of chemotherapy was found to indicate ineffectiveness of the treatment, suggesting a more aggressive therapeutic strategy. The estimation of CA 125 half life after the first two courses of chemotherapy was noted to be a good prognostic factor (9.2 to 10.73 days in patients with total remission, and 22.6 to 44.87 days in patients with progression). The monitoring of ovarian cancer courses using CA 125 level estimations in the serum facilitated decisions at to the timing of the second-look operation; elevated level of the marker was found to indicate that the latter was superfluous. Elevated CA 125 level proceeded clinical diagnosis of relapse by 3 to 6 months, but only in the patients who at earlier stages of the treatment also showed abnormal levels of the marker. The monitoring of patients with complete remission who showed normal CA 125 level throughout the treatment was found useless.     

血清CA125水平测定在预测卵巢上皮性癌复发和预后中的价值

目的 分析卵巢上皮性癌(卵巢癌)患者在初次治疗的不同阶段血清CA125水平与卵巢癌复发和预后的关系.方法 收集2002年1月-2005年12月间浙江大学医学院附属妇产科医院经病理检查证实的151例原发性卵巢癌患者的临床病理资料并进行随访,分析初次治疗的不同阶段血清CA125水平与临床病理参数、2年复发率和5年复发率、5年生存率及无瘤生存期和总生存期的相关性.结果 卵巢癌患者术前血清CA125水平、化疗3个疗程结束时CA125是否降为正常与大多数预后相关的临床病理参数相关,包括分期、病理分级、腹水量、残留病灶大小、复发类型、2年复发率、5年复发率及5年生存率(P均＜0.05).术前及化疗3个疗程结束时血清CA125水平与无瘤生存期和总生存期呈显著性相关(P均＜0.01).但未见手术前后CA125下降幅度与复发和预后的相关性(P均＞0.05).结论 术前及化疗3个疗程结束时血清CA125水平可用于预测卵巢癌的复发和预后.     

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.     

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.     

Interest of CA 125 level in management of ovarian cancer

CA 125 is the most sensitive and the most used marker in the management of ovarian cancer at various stages of the disease. CA 125 is used at the time of diagnosis of the disease, to evaluate the possibility of complete resection during surgery, to estimate sensibility for adjuvant or neo-adjuvant chemotherapy and for diagnosis of recurrences. CA 125 has a diagnostic and therapeutic value and could be of help during therapeutic evaluation. CA 125 has been the topic of many studies for optimizing the management of epithelial ovarian cancers. Mandatory before any ovarian surgery, serum CA 125 levels is a help for the determination of the appropriate surgery. It appears to be a help in choosing therapeutic strategy, to predict optimal surgery and also global and progression-free survival. Low preoperative rates, half-life and fast normalization of CA 125 during the adjuvant chemotherapy are correlated with an optimal surgery and a better global and progression-free survival. The normal range of CA 125 is a strong predictive factor for disease recurrence even if its role in survival has not yet been determined. The dosage of CA 125 and its dynamic interpretation is an indispensable approach to the diagnosis, therapeutics and follow-up of ovarian cancer. Simple serum CA 125 concentration is a very important prognostic and predictive factor for a personalized care.     

血清CA125预测卵巢上皮癌治疗后复发的Meta分析

目的:系统评价血清CA125对卵巢上皮癌综合治疗(手术+化疗)后复发的诊断价值。方法:计算机检索Pub Med、EMBASE、Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CJFD)、中国科技期刊数据库(CSJD)、中国知网(CNKI)数据库,检验医学专业数据库:IFCC循证实验医学数据库、Medion、CRDdatabase、Bandlier Knowledge library等;灰色文献检索:中国学术会议论文库(CACP)、ISTP,检索期限自建库至2015年12月31日。收集有关血清CA125诊断卵巢上皮癌综合治疗后复发的前瞻性或回顾性队列研究。使用诊断性试验准确性质量评价工具(QUADAS)评价文献质量并提取数据,采用Meta-Disc1.4版软件进行Meta分析。结果:共纳入33篇文献,共2188例患者。Meta分析结果显示,血清CA125对卵巢上皮癌治疗后复发的诊断优势比DOR为11.77(95%Cl为7.16~19.37),灵敏度为67%(95%Cl为65%~70%),特异度为83%(95%Cl为80%~85%),阳性似然比为3.83(95%Cl为2.70~5.43),阴性似然比为0.41(95%Cl为0.35~0.49)。结论:血清CA125阴性排除"卵巢癌复发"的价值较大,而阳性诊断"卵巢癌复发"的价值有待进一步确证。     

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.     

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.     

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.