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 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.     

The prognostic value of serum CA 125 in patients with advanced ovarian carcinoma: an analysis of 573 patients by the Medical Research Council Working Party on Gynaecological Cancer

A number of studies have suggested that serum CA 125 levels may be an important prognostic factor for survival of patients with ovarian carcinoma. We investigated, in a large group of patients from 11 UK centers, which combination of CA 125 measurements provided the best prognostic index, and whether the predictive power could be improved by the addition of other factors. Analysis of the data from 248 patients showed that the absolute value of the third CA 125 sample was the single most important factor for predicting progression at 12 months, with the addition of residual bulk only slightly improving the predictive power. Seventy-four patients had CA 125> 70, and of these 57% were correctly predicted to progress or die within 12 months, but 43% remained alive and progression free. The best predictor for progression produced a false positive rate of 19%. We therefore conclude that prognostic information based upon CA 125 measurements up to the start of the third course of initial chemotherapy is not accurate enough to be used to manage individual patients.     

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.     

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.     

The prognostic value of pretherapeutic tetranectin and CA-125 in patients with relapse of ovarian cancer

OBJECTIVE: The aim of the study was to examine the prognostic values of, respectively, tetranectin (TN) and CA-125 measured in serum from patients presenting with relapse of ovarian cancer (OC). METHODS: TN and CA-125 were measured in serum samples from 75 patients with relapse of OC before the start of second-line chemotherapy. The endpoint used was death of OC. The variables were analyzed by univariate life table analysis and multivariate Cox analysis. RESULTS: A significantly shortened survival was found for patients with low serum TN values compared to patients with serum TN levels above one of the cutoff levels. The survivals are illustrated by life tables. No prognostic function was found for CA-125. TN and relapse 相似文献   

A CA125 score as a prognostic index in patients with ovarian cancer

Summary Due to its high specificity (90%) and sensitivity (86%) measurement of CA125 has become well-established in patients with epithelial ovarian cancer. We have formulated a CA125 prognostic score and examined its validity as an additional prognosis index. This score is composed of two CA125 values (one determined preoperatively and one 1 month after operation). CA125 serum levels of 0–64 IU/ml received 1 point, levels of 65–299 IU/ml were given 2 points, and those >300 IU/ml were given 3 points. These points are added to produce the CA125 prognostic score. Statistical comparison demonstrated that patients with scores of 2 or 3 had a significantly (P=0.0005) better prognosis than patients with scores of 4, 5 or 6. The classical prognostics features such as the FIGO stage, residual tumor mass and ascites were found to correlate with the CA125 prognostic score.     

Early CA-125 fluctuations in patients with recurrent ovarian cancer receiving chemotherapy

The objective of this study was to analyze retrospective populations with recurrent ovarian cancer to assess differences in CA-125 patterns during chemotherapy. The populations included all patients treated between January 1994 and January 2004, who received liposomal doxorubicin and topotecan, and all patients treated between July 1997 and June 2001, who received carboplatin. Prognostic variables were abstracted from the medical records. Eighty-nine patients received liposomal doxorubicin and topotecan therapy and 21 received carboplatin; of these, 59 (liposomal doxorubicin), 60 (topotecan), and 17 (carboplatin) patients had evaluable CA-125 patterns. Patients given liposomal doxorubicin were more likely to have received only one or two cycles of therapy (37/89 [42%]) than patients receiving either carboplatin (5/21 [24%]) or topotecan (20/89[22%]). In cycle 1, CA-125 increases in patients were carboplatin, 4/17 (24%); liposomal doxorubicin, 41/59 (69%); and topotecan, 11/60 (18%). In cycle 2, CA-125 increases were carboplatin, 2/16 (13%); liposomal doxorubicin, 19/37 (51%); and topotecan, 9/50 (18%). In cycle 3, CA-125 increases were carboplatin, 0/12 (0%); liposomal doxorubicin, 7/23 (30%); and topotecan, 6/38 (16%). Of patients having any CA-125 decrease and given two or more cycles, fewer declines were seen in those given liposomal doxorubicin precycle 2 (18/35[51%]) than in those given carboplatin (13/16[81%]) or topotecan (49/56[88%]). The most prominent delay in CA-125 decline was in patients given liposomal doxorubicin compared with those given topotecan or carboplatin. In the entire population, only 3 of 107 (2.8%) patients demonstrated first CA-125 decline precycle 4. Discontinuation of therapy solely on the basis of early CA-125 increase (precycle 3), particularly with liposomal doxorubicin chemotherapy, may exclude some patients who will benefit from continued therapy.     

Analysis of failures in patients with stage I ovarian cancer: an Italian multicenter study

Gadducci A, Sartori E, Maggino T, Zola P, Landoni F, Fanucchi A, Stegher C, Alessi C, Buttitta F, Bergamino C. Analysis of failures in patients with stage I ovarian cancer: An Italian multicenter study. Int J GynecolCancer 1997; 7: 445–450.
The objective of this retrospective multicenter study was to assess the rates, times, sites, and risk factors for recurrences in 224 patients with surgical stage I ovarian cancer. Postoperative adjuvant treatment was given to 153 of these patients. One hundred and eighty-two (81.3%) patients are currently alive with no clinical evidence of disease after a median time of 84 months (range, 4–191 months) from surgery, whereas 39 (17.4%) developed recurrent disease after a median time of 29 months (range, 5–112 months). The relapse involved the pelvis in 21 (53.8%) cases, abdomen in 19 (48.7%), pelvic and/or para-aortic lymph nodes in 5 (12.8%), and distant sites in 5 (12.8%). The risk of recurrence was significantly related to FIGO substage ( P < 0.0001) and tumor grade ( P < 0.0001), but not to histological subtype. However, the recurrence rate was lower in mucinous carcinomas (6/52, 11.5%) and higher in clear cell carcinomas (5/14,35.7%). By log-rank test the disease-free survival was significantly related to FIGO substage ( P = 0.0006) and grade ( P = 0.0001). Cox proportional hazard model showed that grade was the only independent prognostic variable for disease-free survival, with a risk ratio for relapse of 2.831 (95% CI, 1.120–6.624) for grade 2 and 7.725 (95% CI, 3.290–18.140) for grade 3, compared to grade 1. In conclusion, tumor grade is the strongest predictor of recurrence in stage I ovarian cancer.     

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     

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.     

CA125 regression in ovarian cancer patients treated with intravenous versus intraperitoneal platinum-based chemotherapy: a gynecologic oncology group study

Objective

CA125 is a non-specific marker of peritoneal irritation which has the potential for false elevation during intraperitoneal treatment. The purpose of this study is to identify the rate of CA125 regression during intraperitoneal (IP) versus intravenous (IV) chemotherapy for ovarian cancer.

Methods

GOG 114, a randomized control trial evaluating IP and IV treatment, includes an intensive CA125 measurement schema with weekly CA125 levels until ≤ 35 units/ml for both IP- and IV-treated patients. Rate of CA125 normalization, median CA125 values for each treatment cycle, as well as clinical and pathologic features were compared between the treatment groups. Baseline CA125 levels and rate of CA125 decline were evaluated with respect to overall survival.

Results

CA125 data were available for 223 patients who received IV cisplatin/paclitaxel and for 231 patients who received IV carboplatin followed by IP cisplatin/paclitaxel. Standard prognostic criteria and baseline CA125 values were similar between the treatment groups. For treatment cycles in which IP-treatment was administered, there was no statistically significant difference in CA125 levels between IV- and IP-treated patients. The rate of CA125 normalization was similar between IV- and IP-treated patients (p = 0.55). Patients with low pre-chemotherapy CA125 levels which rapidly declined during treatment demonstrated a survival advantage (p < 0.0001).

Conclusions

No difference in CA125 decline was identified between IP- and IV-treated patients undergoing a weekly CA125 monitoring schedule. This data supports the utilization of standard CA125 response criteria in the therapeutic monitoring for patients receiving IP treatment.     

CA125在卵巢癌诊断中的应用困境与突破

CA125是应用最广泛的卵巢癌血清标志物。但近年来发现其诊断特异度较低,不少良性疾病患者及妊娠期或月经期妇女血清CA125也明显升高。这一状况给卵巢癌术前诊断及人群筛查带来诸多困扰。鉴于CA125分子是一种高度糖基化的黏蛋白,其糖基化修饰在卵巢癌中具有明显的特征结构,近期研究证实被特征性糖链所修饰的CA125亚型将有助于提高卵巢癌诊断准确度,有望突破上述困境。     

Tumor tissue CA125 in ovarian carcinoma patients with normal serum levels

A good correlation between elevated serum CA125 and its immunolocalization in ovarian tumor tissue has been reported. This study was undertaken in order to assess the presence of CA125 in tumor tissue obtained from ovarian carcinoma patients with normal serum levels. Eleven such ovarian carcinoma patients (nine of them serous) were identified. In seven the level was normal prior to the initial operation, and in four, prior to a positive second-look operation. Immunohistochemical staining of paraffin sections for CA125 was positive in seven of the tumor tissue samples. Tumor tissue of most ovarian carcinoma patients with a preoperative normal serum CA125 contains the antigen, but an undetermined mechanism prevents elevated serum levels.     

Whole-body positron emission tomography and tumor marker CA125 for detection of recurrence in epithelial ovarian cancer

Abstract.   Murakami M, Miyamoto T, Iida T, Tsukada H, Watanabe M, Shida M, Maeda H, Nasu S, Yasuda S, Yasuda M, Ide M. Whole-body positron emission tomography and tumor marker CA125 for detection of recurrence in epithelial ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 99–107.
We evaluated the clinical role of the combination of positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and tumor marker CA125, in the detection of recurrence after initial therapy for epithelial ovarian cancer. The indication is the cases that cannot be confirmed the recurrence by conventional imaging modalities. Ninety patients underwent PET and computed tomography, including the measurement of specific tumor markers. FDG-PET confirmed recurrence in 46 patients (51%), and the recurrent site was confirmed by PET alone in 17 (37%). PET had high sensitivity for detecting both intraperitoneal and retroperitoneal metastases (93.9 and 92.9%, respectively). PET imaging was able to detect normal-sized metastases in the lymph nodes in 14 (50%) of the 28 patients with retroperitoneal metastasis. PET could show 87.5% positive rate of recurrent patients with asymptomatic rise of CA125 who had no sign of recurrence by conventional imaging methods. Of the 46 recurrent patients, 41 (89%) had specific elevated titers of CA125 at the first treatment. PET imaging was able to detect recurrence at relatively low titers (a median 68 U/mL) of CA125. In 8 (19.5%) of these 41 patients, recurrence with normal CA125 levels could be confirmed only by PET. The sensitivity of the combination of PET and CA125 was 97.8% with only one false-negative case. The combination of FDG-PET and CA125 titer is useful for the accurate detection of recurrence.     

CA125 surveillance increases optimal resectability at secondary cytoreductive surgery for recurrent epithelial ovarian cancer

Objective

Recent data suggest that serial CA125 surveillance following remission in asymptomatic patients with epithelial ovarian cancer (EOC) does not impact overall survival. However, earlier detection of recurrence may influence resectability at secondary cytoreductive surgery (SCS). We hypothesized that a shorter time interval between CA125 elevation and SCS correlates with a higher likelihood of optimal resection among eligible patients.

Methods

We identified patients with recurrent epithelial ovarian cancer who underwent SCS from 1995 to 2009 at our institution. All patients initially underwent primary cytoreductive surgery followed by platinum-based chemotherapy. CA125 elevation was considered the first value two-times the patient's nadir level. Our “study interval” was the time between CA125 elevation and SCS. Optimal SCS was defined as microscopic residual disease (≤ 0.5 cm). Our analysis compared patients who underwent optimal vs. suboptimal SCS.

Results

Seventy-four patients who underwent SCS for recurrent EOC met inclusion criteria. Median disease-free interval prior to SCS was 19 vs. 12 months for the optimal and suboptimal SCS groups. More patients undergoing suboptimal SCS had ascites (21% vs. 2%, p = 0.01) and carcinomatosis (42% vs. 5%, p < 0.0001). Patients who underwent optimal SCS went to the operating room 5.3 vs. 16.4 weeks (HR 1.03, 95% CI 1.01-1.06, p = 0.04) from the time of their CA125 elevation. Optimal SCS was associated with a longer overall survival (47 vs. 23 months, p < 0.0001).

Conclusions

Each week delay after first CA125 elevation correlated with a 3% increased chance of suboptimal resection at SCS. Serial CA125 surveillance for early detection of recurrence may increase rates of optimal SCS and potentially influence overall survival.     

Screening for ovarian cancer using serum CA125 and vaginal examination: report on 2550 females

This study was undertaken to assess the effectiveness of using serum CA125 and vaginal examination as a screening test for ovarian cancer in apparently healthy females. Two thousand five hundred and fifty healthy females aged 40 and over were recruited to participate in a screening study involving a questionnaire, serum CA125 measurement and vaginal examination. Females with either an elevated CA125 level or abnormal vaginal examination had a pelvic ultrasound performed as a secondary procedure. The positive predictive values of an elevated serum CA125 level, and a combination of CA125 level measurement and vaginal examination for ovarian cancer, were 1/100 and 1/3, respectively. The specificities of serum CA125 levels, vaginal examination and both in combination were 96.1%, 98.5% and 99.9%, respectively. In postmenopausal females the positive predictive values were improved with CA125 measurement alone, giving a positive predictive value of 1/24. Seventeen females underwent operative procedure as a result of the screening—only one of these was for an ovarian cancer. The combination of serum CA125 measurement and vaginal examination is not an effective screening test in the general population, although in postmenopausal females it does achieve acceptable specificities and positive predictive values.