Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.     

The utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer

The objective of this study was to evaluate the ability of a preoperative serum CA125 to predict whether optimal debulking (OD) could be achieved for patients with stage III and IV epithelial ovarian cancer (EOC). The records of consecutive patients who underwent primary surgery for EOC at Indiana University Hospital between January 1997 and January 2003 were reviewed. Eligibility criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. The Medcalc software statistical package was used to generate a receiver-operating characteristic (ROC) curve. Two hundred and eighty-nine cases of stage III/IV EOC were identified, of which 164 met the eligibility criteria. Serum CA125 /=75% of the time. Conversely, OD was achieved in /=4500. The area under the ROC curve for CA125 was .670. The OD rate for those with and without ascites was 49% and 79%, respectively (P < 0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.686. We conclude that preoperative serum CA125 did not reliably predict OD in patients with stage III-IV EOC.     

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。     

RETRACTED: A study to evaluate the utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer

OBJECTIVE: To determine the ability of a preoperative serum CA125 to predict optimal primary tumor cytoreduction in patients with stage III and IV epithelial ovarian cancer (EOC). MATERIALS AND METHODS: The records of patients with advanced stage who underwent primary surgery for EOC at Tehran University, Vali-Asr Hospital between 2000 and 2002 were reviewed. Inclusion criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. Without optimal cytoreduction was determined using the receiver operator curve (ROC). RESULTS: One hundred and twenty cases of advanced stage EOC were identified, of which 90 cases of stage III/IV met our inclusion criteria. Serum CA125 < or = 400 was identified with OD > or = 75% of the time. Conversely, optimal cytoreduction was performed in < or = 40% of patients with CA125 > or =4000. The area under the ROC curve for CA125 was 0.680. The optimal cytoreduction rate for those with and without ascites was 38% and 77%, respectively (P<0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.696. CONCLUSION: We conclude that CA125 level did not reliably predict optimal cytoreduction in patients with stage III-IV EOC.     

CA 125 regression after two cycles of neoadjuvant chemotherapy as prognostic factor in patients with advanced ovarian cancer and primary peritoneal serous cancer who underwent interval surgical cytoreduction

OBJECTIVES: The aim of our study was to assess the prognostic role of CA 125 regression during neoadjuvant chemotherapy (NAC) in patients with ovarian cancer (OC) or primary peritoneal serous carcinoma (PPSC) that underwent interval debulking surgery (IOC). MATERIAL AND METHODS: Thirty one patients with advanced OC or PPSC (FIGO stage IIIC and IV) who underwent initial exploratory surgery, followed by NAC containing platinum analogs, have been analyzed, retrospectively. We have used a regression coefficient (RCA 125), which was calculated as following: log10 (CA 125 level measured after two cycles of NAC/baseline CA 125) for statistical analysis. The median value of RCA 125 reached -0.788 and has been used to dichotomize. Optimal IOC has been performed in 67.74% (21/31) patients, suboptimal in 25.81% (8/31) patients and 6.45% (2/31) of patients did not undergo IOC due to the progression of the disease. RESULTS: We have noted significant correspondence between time to progression and RCA 125 in univariate analysis, which we have also confirmed in multivariate analysis (HR 0.27; 95% CI, 0.15-0.96; p = 0.0178). Similarly, we have observed significant relationship between overall survival, RCA 125 and extension IOC in univariate analysis. Multivariate analysis confirmed that RCA 125 was independent prognostic factor, HR-0.18 (95% CI, 0.07-0.56; p = 0.004). In case of patients with high RCA 125, a greater rate of optimal debulking cytoreduction (p = 0.0278, U = 50.0) has been observed. CONCLUSIONS: RCA 125 after two courses of NAC appears to be an important prognostic factor in patients with OC or PPSC, who underwent IOC High RCA 125 during NAC seems to be a good predictive factor in order to achieve optimal IOC.     

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

Objective

To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery.

Methods

Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated.

Results

The 124 enrolled patients had a median age of 62 years (range, 35–79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR] = 1.94, p = 0.003), residual cancer at the end of surgery ≥ 1 cm (HR = 3.78, p < 0.001), and histological grade 0–1 (HR = 1.65, p = 0.03) were independent predictors of decreased OS. Grade 0–1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio = 8.42, p = 0.003).

Conclusions

Residual disease of ≥ 1 cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.     

Preoperative CA-125 level as a predictor of non optimal cytoreduction of advanced epithelial ovarian cancer

BACKGROUND: Suboptimal cytoreduction of advanced ovarian cancer is related to initial tumor bulk which correlates with CA125 level. METHODS: Retrospective record study of 40 patients with stage III ovarian cancer. The ability of a CA125 threshold level of 500 U/mL to predict suboptimal cytoreduction was determined. RESULTS: Twenty-four (60%) of the patients were optimally cytoreduced. At the CA125 cut off level of 500 U/mL the sensitivity for predicting suboptimal debulking was 62% and specificity was 83%. Above a CA 125 level of 1500 U/mL none of the patients were optimally cytoreduced. CONCLUSIONS: More data are needed to determine the CA125 cut off level at which the standard approach of initial laparotomy and cytoreduction may be modified.     

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.     

CA125 decline in ovarian cancer patients treated with intravenous versus intraperitoneal platinum-based chemotherapy

ObjectivesTo compare the slope of CA125 decline in patients with optimally debulked epithelial ovarian cancer achieving a response to intravenous (IV) versus intraperitoneal (IP) platinum-based chemotherapy. The secondary objectives are to determine if the time to normal CA125 levels and time to nadir of CA125 differ between the groups.MethodsPatients with primary stage III, optimally cytoreduced ovarian cancer were stratified as to whether platinum and taxane chemotherapy was administered entirely IV (IV group), or whether it was given IV and IP (IP group). Inclusion criteria included an elevated CA125 prior to surgery or first cycle chemotherapy and at least 1 month follow-up after completion of chemotherapy. All patients had a complete or partial response. In addition, IP patients had to have received at least 1 cycle of IP chemotherapy. Because of the large range of CA125 levels, raw CA125 values were natural log transformed and compared using repeated measures analysis of variance (ANOVA).Results53 patients met inclusion criteria, 36 in the IV arm and 17 in the IP arm. The median number of chemotherapy cycles was 6 in both groups; the range was 5–9 in the IP arm and 6–10 in the IV arm. The median CA125 prior to surgery was 888 (range 45–5940) in the IP group and 1081 (range 58–19,440) in the IV group, p = 0.55. After surgery but prior to chemotherapy, the median CA125 was 175.5 in the IP arm (range 10.8–4035) versus 233.5 (range 16.5–6890) in the IV arm, p = 0.43. The median time to normalization of CA125 for the IP group was half the time of the IV group, 0.75 months (range 0 to 4.5) versus 1.5 months (range 0 to 6.25), p = 0.15. The time to nadir was slightly faster in the IP arm as compared to the IV arm, 4.5 months (2–10.5) versus 6 months (2–14), p = 0.13. The CA125 slopes were parallel, indicating that the CA125 levels declined at the same rate in both groups. However, the patients treated with IP chemotherapy had significantly lower CA125 levels over all the cycles, p = 0.02.ConclusionsContrary to the assumption that IP chemotherapy elevates CA125 levels due to peritoneal irritation, these results show a trend towards faster time to CA125 normalization and nadir, and significantly lower CA125 levels during therapy for patients responding to IP chemotherapy compared with patients responding to IV therapy.     

新辅助化疗在晚期卵巢上皮性癌综合治疗中的临床研究

目的探讨新辅助化疗(NACT)在晚期卵巢上皮性癌(卵巢癌)治疗中的临床意义。方法回顾性分析四川省肿瘤医院1999年1月至2008年12月收治的晚期卵巢癌(FIGOⅢ、Ⅳ期)患者161例,其中73例接受新辅助化疗+手术治疗+化疗(研究组),88例行初次肿瘤细胞减灭术+化疗(传统组)。结果研究组肿瘤手术切除率(即理想减瘤率)77.1%,传统组为56.8%,差异有统计学意义(P=0.012)。研究组术中失血量、术中输血量、术中补液量、腹水量和手术时间与传统组比较,差异均有统计学意义(P<0.05)。研究组平均无进展生存期(PFS)和总体生存期(OS)分别为22.7(7～63.5)个月和33.5(13.8～92.3)个月,传统组分别为21.7(4.3～61.2)个月和32.1(12.4～114.9)个月,两组比较差异无统计学意义(分别为P=0.082和P=0.293)。研究组和传统组5年生存率分别为17.8%和11.4%,差异无统计学意义(P=0.503)。结论行新辅助化疗+手术治疗+化疗治疗晚期卵巢上皮性癌的PFS、OS与仅行初次肿瘤细胞减灭术+化疗相似,但前者能明显提高肿瘤的手术切除率、减少术中出血量,同时并没有增加手术的并发症。     

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.     

Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis

OBJECTIVE: To determine the overall survival and relative effect of multiple prognostic variables in cohorts of patients with advanced-stage ovarian cancer treated with platinum-based neoadjuvant chemotherapy in lieu of primary cytoreductive surgery. METHODS: Twenty-two cohorts of patients with Stage III and IV ovarian cancer (835 patients) were identified from articles in MEDLINE (1989-2005). Linear regression models, with weighted correlation calculations, were used to assess the effect on median survival time of the proportion of each cohort undergoing maximum interval cytoreduction, proportion of patients with Stage IV disease, median number of pre-operative chemotherapy cycles, median age, and year of publication. RESULTS: The mean weighted median overall survival time for all cohorts was 24.5 months. The weighted mean proportion of patients in each cohort undergoing maximal interval cytoreduction was 65.0%. Each 10% increase in maximal cytoreduction was associated with a 1.9 month increase in median survival time (p=0.027). Median overall survival was positively correlated with platinum-taxane chemotherapy (p<0.001) and increasing year of publication (p=0.004) and negatively correlated with the proportion of Stage IV disease (p=0.002). Each incremental increase in pre-operative chemotherapy cycles was associated with a decrease in median survival time of 4.1 months (p=0.046). CONCLUSIONS: Neoadjuvant chemotherapy in lieu of primary cytoreduction is associated with inferior overall survival compared to initial surgery. Increasing percent maximal cytoreduction is positively associated with median cohort survival; however, the negative survival effect of increasing number of chemotherapy cycles prior to interval surgery suggests that definitive operative intervention should be undertaken as early in the treatment program as possible.     

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.     

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.     

Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer

Objective

This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level.

Methods

We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group.

Results

The NAC group had more FIGO stage IV disease (P < 0.001) and higher CA-125 levels (P < 0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P < 0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis (P = 0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (> 2000 U/ml; HR 0.62, P = 0.037).

Conclusion

Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer.     

Impact of neoadjuvant chemotherapy cycles prior to interval surgery in patients with advanced epithelial ovarian cancer

Objectives

Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients.

Methods

Data from EOC patients (stages IIIC–IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (< 4 = group B1; > 4 = group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed.

Results

367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p < 0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p < 0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p < 0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p < 0.001)) with an independent impact from disease stage and WHO performance status.

Conclusions

Patients with advanced EOC receiving complete IDS after more than 4 cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.     

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.