Serum half-life of the tumor marker CA 125 during induction chemotherapy as a prognostic indicator for survival in ovarian carcinoma

Patients (n = 72) with newly diagnosed non-mucinous ovarian carcinomas, FIGO stages IIC-IV, and CA 125 levels raised when starting chemotherapy were followed both by serial serum CA 125 tumor marker determinations during induction chemotherapy and by second-look operation after 4-6 cycles of chemotherapy. Patients with complete response at the second-look operation (n = 19) had an estimated survival of 75% 59 months after the operation, compared with 22% in the 53 patients with persisting disease (p = 0.0004). Patients (n = 23) with a serum CA 125 half-life shorter than 16 days during induction chemotherapy had an estimated survival of 68% 59 months after the second-look operation as compared with 18% in 49 patients with a CA 125 half-life of more than 16 days (p = 0.003). Thus both second-look operation and serial CA 125 measurements fairly accurately predicted the patient survival, although the groups of patients identified by the two methods differed slightly. There was a strong correlation between the second-look results and the residual tumor after the primary operation. Interestingly, this association could not be found for tumor marker pattern, which could mean that this is an independent prognostic factor.     

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.     

晚期卵巢上皮性癌患者初次治疗过程中血清CA125水平变化与其预后的关系

目的 探讨晚期(Ⅲ～Ⅳ期)卵巢上皮性癌(卵巢癌)患者初次治疗过程中血清CA125水平变化与其预后的关系.方法 选择1998年1月-2003年12月间中山大学肿瘤防治中心妇瘤科收治的142例晚期卵巢癌患者,回顾性分析其初次治疗过程中血清CA125水平的变化,采用Kaplan-Meier法计算其累积生存率,并采用Cox风险比例回归模型分析血清CA125水平的变化对患者预后的影响.结果 根据患者治疗前血清CA125水平不同分为≤500、>500～1500和>1500 kU/L,其3年累积生存率(分别为64%、71%及64%)比较,差异无统计学意义(P>0.05).术后接受3个疗程化疗后,血清CA125水平降至正常(0～35 kU/L)的77例患者的3年及5年累积生存率分别为84%及56%,明显高于血清CA125水平仍为异常的48例患者(分别为42%、15%,P<0.01).多因素分析表明,残留灶直径(P<0.01)及3个疗程化疗后血清CA125水平(P<0.01)是影响晚期卵巢癌患者预后的独立的因素.进一步分层分析表明,接受了满意的肿瘤细胞减灭术(残留灶直径≤1 cm)的患者中,3个疗程化疗后血清CA125水平降至正常者的3年及5年累积生存率分别为88%、64%,明显高于化疗后血清CA125笛水平仍为异常者(分别为52%、18%,P<0.01);同样,接受了不满意的肿瘤细胞减灭术(残留灶直径>1 cm)的患者中,3个疗程化疗后血清CA125水平降至正常者的3年和5年累积生存率分别为74%、32%,明显高于化疗后血清CA125水平仍为异常者的33%、13%(P<0.01).结论 3个疗程化疗后血清CA125水平正常与否可预测晚期卵巢癌患者的预后,且无论初次手术是否为满意的肿瘤细胞减灭术,3个疗程化疗后血清CA125水平降至正常者较未降至正常者预后好.     

血清CA125半衰期判定卵巢上皮性癌预后的价值

目的 探讨血清ＣＡ１２５半衰期在卵巢上皮性癌中的预后价值。方法 回顾性分析３０例卵巢上皮性癌患者在化疗过程中血清ＣＡ１２５半衰期值（ｔ１／２）与生存时间的关系。结果 血清ＣＡ１２５半衰期值（ｔ１／２）≤２０天组的中位生存时间为３６个月，ｔ１／２〉２０天组中完全缓解率为２７．３％，两者存在极显著差异（ｐ＝０．００１）。多因素生存分析表明：ＣＡ１２５半衰期和细胞分级、残余瘤灶大小均是独立的预后因素。结     

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.     

The predictive and prognostic value of serum CA 125 half-life during paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma

OBJECTIVES: Serum CA 125 kinetics during early chemotherapy has a strong predictive and prognostic relevance for patients with advanced ovarian carcinoma who received a first-line platinum-based regimen, whereas the ability of serum CA 125 assay to reflect the response to paclitaxel-based chemotherapy has not yet been defined. The aim of the present paper is to calculate the serum CA 125 half-life during first-line paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma and to correlate this kinetic parameter with the response to treatment, progression-free survival and overall survival. METHODS: This retrospective investigation assessed 71 patients with stages IIc-IV ovarian carcinoma who underwent initial surgery followed by paclitaxel/platinum-based chemotherapy and who had serum CA 125 > 35 U/ml before the first cycle of chemotherapy. Only epithelial ovarian cancers were included. RESULTS: The 25%, 50%, and 75% quantiles of serum CA 125 half-life during early chemotherapy were 10, 14, and 20 days, respectively. Taking the value corresponding to the 50% quantile (i.e., 14 days) as cutoff limit, serum CA 125 half-life was an independent prognostic factor for the chance of achieving a complete response to treatment as well as for progression-free survival and overall survival. In detail, patients with serum antigen half-life <== 14 days had a 3.362 times as great probability to achieve a complete response and a 3.113 times as low probability to die when compared to those with a longer half-life. CONCLUSIONS: Serum CA 125 assay represents a reliable biochemical tool for the management of advanced ovarian carcinoma patients who receive a first-line paclitaxel/platinum-based chemotherapy.     

CA 125 for the monitoring of ovarian carcinoma during primary therapy

Thirty-one patients with ovarian cancer were monitored with the CA 125 antigenic determinant in the interval between cytoreductive surgery and the completion of subsequent chemotherapy. Distinct CA 125 assay trends have emerged from prospective serial monitoring. Among patients who were clinically and surgically free of disease after the completion of cytoreductive chemotherapy, the CA 125 assay always fell to levels under 35 U/mL within the first three months of cytoreductive chemotherapy, and stayed at low levels. Patients with partial cytoreduction operations had decreases in serum CA 125 levels only if there was a response to further therapy. The rate of fall of the CA 125 levels correlated with clinical outcome. All 13 patients with serum CA 125 above 35 U/mL after three months of treatment invariably had persistent tumors after subsequent chemotherapy, whereas in patients showing reduction of the CA 125 to levels below 35 U/mL, there were no surgically detectable tumors. Measurement of CA 125 during treatment might permit an early change to alternative and optimal forms of therapeutic management. The CA 125 level three months after treatment appears to be a critical predictor of response to therapy.     

The prognostic significance of the half-life of serum CA 125 in patients responding to chemotherapy for epithelial ovarian carcinoma

Various prognostic factors were studied in 29 patients with stage III or IV ovarian cancer who responded to initial chemotherapy after initial diagnostic surgery. The half-life of CA 125 in serum during initial chemotherapy was the most important prognostic indicator for survival (P less than 0.001) and the chance of achieving complete remission (P = 0.012). A CA 125 half-life of less than 20 days, 20-40 days and greater than 40 days appears to identify patients with a good, intermediate or poor prognosis, the two year actuarial survival being 76%, 48% and 0% respectively. The change of achieving a complete remission was 15% and 67% respectively for patients with a serum CA 125 half-life of greater than 20 or less than 20 days.     

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.     

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.     

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.     

Combined prognostic importance of CA 125, histopathologic grade and DNA-index in advanced ovarian cancer

PURPOSE: To analyse the possible prognostic importance of a combination of serum CA 125 levels, tumor cell DNA distribution and histopathologic grade in patients with epithelial ovarian cancer. METHOD: The study included 41 patients with ovarian cancer stages II-IV. CA 125 was measured before the start of chemotherapy and after every course. The DNA distribution was analysed by flow cytometry in biopsy specimens from the primary tumour. The histopathologic grading was performed according to WHO criteria. RESULTS: The CA 125 level was of major prognostic significance. All patients with an abnormal value (> 35 U/ml) after three courses died within 16 months. The DNA distribution did not add significant prognostic information, but the histopathologic grade was of significant prognostic importance as investigated by Cox analysis. CONCLUSION: CA 125 is an important prognostic marker in epithelial ovarian cancer. The value after three courses of chemotherapy is significant. The histopathologic grade adds further prognostic information.     

Evaluation of serum CA 125 levels in the monitoring of ovarian cancer

Serum CA 125 levels were evaluated in 227 patients with ovarian cancer. CA 125 levels were elevated in 86% of the patients. All histologic types, including mucinous tumors, were associated with raised CA 125 levels. There was a positive correlation with tumor burden and an inverse correlation with degree of differentiation. In patients undergoing radical operation an elevated CA 125 level was a bad prognostic index. Serial CA 125 measurements were assessable in 112 patients undergoing chemotherapy. Rising or falling levels correlated with disease in 92% of the cases. The CA 125 level increased before clinical progression with a median lead time of 3 months. Only patients who showed objective response to chemotherapy had a decrease in antigen levels of greater than or equal to 30% 4 weeks after the first course of chemotherapy and a normalization of CA 125 levels 3 months after initiation of chemotherapy. Rising levels were always associated with progression. These data suggest that CA 125 may aid in early identification of nonresponders. However, a normal CA 125 level does not exclude the presence of disease.     

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.     

卵巢上皮性癌新辅助化疗后血清CA125水平下降至一半所需的时间与手术切净率及预后的关系

目的 探讨卵巢上皮性癌新辅助化疗后血清CA125,水平下降至一半所需的时间（即CA15的T1/2）与手术切净率及预后的关系。方法 回顾性分析39例行新辅助化疗的卵巢上皮性癌患者,以化疗后CA125的T1/2长短分组,分为T1/2〈20d组和T1/2≥20d组,比较两组间的手术切净率及预后。结果 新辅助化疗后T1/2≥120d组的手术切净率明显低于T1/2〈20d组（分别为29％和80％,P〈0．01）。T1/2≥20d组的中位生存时间为21.2个月,明显低于T1/2〈20d组的37．6个月（P〈0．05）;两组累计生存率比较,差异有统计学意义（P〈0．01）。多因素分析提示,血清CA125的T1/2及术后残留灶直径是卵巢上皮性癌患者新辅助化疗后影响其预后的独立因素。结论 卵巢上皮性癌新辅助化疗后,血清CA125的T1/2长短有助于术前判断手术切净情况,并且是影响此类患者预后的独立因素。     

Ovarian cancer: the prognostic value of the serum half-life of CA125 during induction chemotherapy

Eighty-five patients with epithelial ovarian cancer were studied to assess the prognostic value of the prechemotherapy serum concentration of CA125 and its half-life during induction therapy. The endpoints of the analysis were progression rate and time to progression. The prechemotherapy CA125 level had no prognostic value (P = 0.36) if the patients were stratified for tumor size. The half-life of CA125, however, was an independent prognostic variable (P = 0.01). Patients with a half-life of 20 days and more had a 3.2 times higher progression rate and a significantly shorter median time to progression of only 11 months, as compared to 43 months for patients with a half-life of less than 20 days.     

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.     

Prognostic value of serial CA125 measurements during chemotherapy for patients with advanced ovarian cancer

Serum CA125 concentrations measured before and during chemotherapy may provide additional information for prognostic assessment of patients with epithelial ovarian cancer (EOC), and enable discrimination between patients who are likely to benefit from further therapy and those who will not. Medical records of 40 patients with advanced EOC, treated at the Department of Obstetrics and Gynecology of the University Hospital Nijmegen between July 1984 and April 1993, were examined. All patients had primary cytoreductive surgery followed by platinum-based chemotherapy. Serum samples were obtained before surgery and during chemotherapy. Follow-up information and patient and tumor characteristics were abstracted from medical records until December 1, 1994. By using multivariate Cox proportional hazards models for disease-free and overall survival it was evaluated whether outcome prediction was improved by inclusion of serum CA125 quantitations.
  Only FIGO stage and extent of residual tumor were significant independent prognostic factors before the start of chemotherapy. When such regression models were constructed after subsequent courses of chemotherapy, serum CA125 measurements conducted after each of the first three chemotherapy courses improved the prediction of disease-free survival. Prediction of overall survival was improved by inclusion of serum CA125 measurements after courses 1–6. Inclusion of serum CA125 measurements during chemotherapy improved prognostic assessment of patients with advanced EOC.     

CA125 regression during neoadjuvant chemotherapy as an independent prognostic factor for survival in patients with advanced ovarian serous adenocarcinoma

OBJECTIVE: The associations of the CA125 regression rate with initial response to chemotherapy and prognosis remain unclear. We examined the association between CA125 regression in neoadjuvant chemotherapy (NAC) and prognosis. METHODS: Fifty patients with advanced ovarian cancer (TNM classification TIIIc or M1) who received initial NAC and did not undergo significant cytoreductive surgery were selected for the retrospective analysis, after excluding clear cell carcinoma and mucinous adenocarcinoma putative to be cisplatin-resistant. For each patient, regression coefficient was calculated using all the CA125 levels measured from the day of NAC as day 0 until the day of normalization of CA125 level (<35 IU/ml) or the day of standard surgery. Responder was defined as a regression coefficient of -0.039 or greater (33 cases) and nonresponder as a regression coefficient less than -0.039 (17 cases). RESULTS: The 3-year survival rate for all 50 cases was 59.3%. When stratified by regression coefficient of CA125 levels, the 3-year survival was 70.5% in responders and 43.3% in nonresponders. Univariate analysis identified the regression coefficient of CA125 as a significant prognostic factor for overall survival (P = 0.012; log lank test). Residual tumor at standard surgery after NAC and absolute CA125 level were not significant prognostic factors. CONCLUSIONS: Based on the CA125 regression rate, it is possible to stratify TIIIc or M1 ovarian serous adenocarcinoma cases into those with a good prognosis of survival and those with poor prognosis. Regression coefficient of CA125 level greater than -0.039 predicts good 3-year survival after subsequent radical surgeries.     

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.