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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 27-30

Prognostic Value of Pretreatment CA 125 in Patients of Ovarian Carcinoma


1 Senior Resident, Dept. of Gynecological Oncology, IGIMS, India
2 Additional Professor, Dept. of Gynecological Oncology, IGIMS, India
3 Additional Professor, Dept. of Pathology, IGIMS, India
4 Associate Professor, Dept. of RCC, IGIMS, India
5 Assistant Professor, Dept. of Surgical oncology, IGIMS, India
6 Assistant Professor, Dept. of Community Medicine, IGIMS, India

Date of Web Publication20-Nov-2020

Correspondence Address:
Sangeeta Pankaj
Additional professor, Dept. of Gynecological Oncology, IGIMS, Patna
India
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Source of Support: None, Conflict of Interest: None


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  Abstract 


Introduction: In patients with epithelial ovarian cancer (EOC) , the volume of residual tumour after debulking is the prognostic factor for survival. We examined the relationship between postoperative decline in serum cancer antigen(CA125) and residual disease after cytoreductive surgery and evaluate post operative changes in serum CA125 levels as predictor for disease-specific survival.
Material and methods: This retrospective study consisted of evaluation of serum CA125 in 173 patients with EOC treated with cytoreductive surgery, either primary or secondary surgery after neoadjuvant treatment between June 2015 and Jan 2018 in a tertiary care centre of Bihar. Preoperative and postoperative CA125 value were recorded and simultaneous diagnosis of histological subtype, clinical stage and differentiation grade of the tumour (n=173) were studied in order to determine the prognostic value of CA125.
Result: We found irresectable mass in 58 EOC patients out of which 56(96.55%) had preoperative CA125 >500 [p <0.001]. A postoperative decline in serum CA125 level of ?80% was associated with complete primary cytoreduction (p=0.035). On analyses there was favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction [p < 0.001].
Conclusion: The current retrospective study suggests that the preoperative CA125 value determine the resectability of ovarian mass and also post operative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent cytoreductive surgery for EOC.

Keywords: CA125 Antigen, Epithelial ovarian cancer, Prognosis, Residual, Survival


How to cite this article:
Kumari J, Pankaj S, Kumari A, Kumari A, Nazneen S, Choudhary V, Devi S, Kumar M, Kumar S. Prognostic Value of Pretreatment CA 125 in Patients of Ovarian Carcinoma. J Indira Gandhi Inst Med Sci 2019;5:27-30

How to cite this URL:
Kumari J, Pankaj S, Kumari A, Kumari A, Nazneen S, Choudhary V, Devi S, Kumar M, Kumar S. Prognostic Value of Pretreatment CA 125 in Patients of Ovarian Carcinoma. J Indira Gandhi Inst Med Sci [serial online] 2019 [cited 2021 Feb 25];5:27-30. Available from: http://www.jigims.co.in/text.asp?2019/5/1/27/301072




  Introduction: Top


Epithelial ovarian carcinoma (EOC) is the most lethal genital tract tumour, with more than 150,000 deaths worldwide.[1] Approximately 75% of patients diagnosed with epithelial ovarian cancer have advanced stage disease[2], resulting in 5- year survival rates of just 17%-36%.[3] In India age- standardised incidence rate of ovarian cancer is 4.9 and age standard mortality rate is 3.6 according to GLOBOCON 2012. It is the most frequently encountered cause of gynaecological cancer death, and the fifth leading cause of cancer deaths in developing countries.[4] Management of advanced stage ovarian cancer consists of surgical cytoreduction and postoperative chemotherapy or neoadjuvant chemotherapy followed by interval debulking. Serial measurements of CA125 are routinely used to monitor tumour response during chemotherapy, survival being correlated with CA125 decline.[5] In surgery the volume of the residual tumor after debulking is known as the most important prognostic factor for survival.[6],[7] However, the definition of residual disease is subjective, as any estimate of residual tumour volume is based on the surgeons intraoperative assessment. Two studies exploring the clinical significance of changes in serum CA125 levels during the post-operative period report that a reduction of ≥80% immediately after surgery is an independent prognostic factor for progression-free survival (PFS).[8] However, studies examining the correlation between the change in post-operative serum CA125 levels and the extent of disease after surgery report conflicting results.[9],[10],[11]

The objectives of the present study were

  1. To determine the resectibilty of mass according to preoperative CA125 level.
  2. To investigate the relationship between the postoperative decline in serum CA125 levels and the residual tumor volume after cytoreductive surgery in patients with advanced stage epithelial ovarian cancer, and
  3. To determine the value of post-operative changes in CA125 levels for predicting disease-specific survival.



  Material and Method: Top


Design and selection of patients

This retrospective study was carried out in a tertiary care centre of Bihar, from June 2015 to Jan 2018. The medical records of patients with epithelial ovarian cancer of any age group who were treated with cytoreductive surgery either primarily or followed by neoadjuvant chemotherapy in the department were taken. Primary debulking surgery was the treatment of choice for patients with advanced stage ovarian cancer. When complete or at least optimal (≤1 cm) tumor resection could not be possible based on imaging and patient's performance status, treatment with neoadjuvant chemotherapy followed by interval debulking surgery was chosen. Patients were included if the pre- and postoperative serum CA125 levels were documented. Patients were excluded if no data were available regarding pre- and/or postoperative CA125 levels or surgery outcome.

Serum levels of CA125 were determined by chemiluminescent enzyme immunoassay (Immunolite OM-MA, Siemens Healthcare), considering CA125 values higher than 35 U/mL as abnormal.


  Data Collection: Top


Age of the patients, tumor characteristics at primary diagnosis (tumor histology and grade, FIGO stage), data of the surgery (intra-operative volume of ascites, extensiveness of surgery, residual disease after primary surgery as documented by the surgeon); pre- and postoperative serum CA125 level; type of chemotherapy; and follow-up data were taken.

Perioperative changes in CA125 levels

Correlation of preoperative serum CA125 with resectibility of ovarian mass were determined by this data. Perioperative changes in serum CA125 levels were calculated as difference between pre- and postoperative values. To determine the effect of surgery on serum CA125 levels, pre- and postoperative measurements were performed as close to the date of surgery as possible and before the initiation of adjuvant chemotherapy. If more than one serum CA125 level was documented before surgery, the value closest to the date of surgery was used for analyses. When more than one postoperative CA125 value was retrieved from the records, the value obtained immediately before the initiation of adjuvant chemotherapy was used. In addition, the percentage reduction in the serum CA125 level was calculated for each patient. The study population was then categorized into three groups based on changes in serum CA125 levels: ≥80% reduction; 50%-79% reduction; and <50% reduction. Fifteen patients in whom the serum CA125 level increased postoperatively were included in the latter category.


  Statistic Analysis: Top


The statistical methods used to analysis the data include number, percentage, mean, geometric mean (CI, confidence interval), The chi-squared test was used to compare relative reductions in CA125 levels according to the three categories outlined above (≥80%, 50%-79% and <50% reductions). To calculate disease-specific survival, the follow-up time in months was calculated for each patient as follows: the time from the date of primary cytoreductive surgery to the time of cancer-related death (event cases), or the time of the last recorded follow-up visit or death from other cause (censored observations), which ever occurred first. The protocol of the study was approved by the Ethical Committees


  Result: Top


187 patients with ovarian cancer who operated from June 2015 to January 2018 in a tertiary care centre of Bihar, were included in the study. Medical record of post operative CA125 of all these patients were available. 14 patients were lost to follow up and they were excluded from survival analysis and 173 patients were included in the study. The geometric mean of the preoperative CA125 concentration was 650 U/mL (95% CI 504-837 U/mL) and the median time from preoperative CA125 sampling to primary surgery was 11 days (range 0-20 days). The median time from surgery to postoperative serum CA125 measurement was 16 days (range 5-34 days) with a geometric mean of 197 U/mL (95% CI 159-243 U/mL).

Decline in serum CA125 levels and residual tumor volume after primary surgery

The majority of patients experienced a decline in serum CA125 levels after surgery. Comparisons showed that pre- and postoperative serum CA125 levels were both significantly higher in the group of patients with an inadequate outcome of surgery. This was shown in [Table 4]. The height of the serum CA125 levels in the latter group were decreasing linearly across those with optimal and complete cytoreduction (p=0.034 and <0.001 for pre- and postoperative values, respectively). However, the absolute decline in serum CA125 levels was similar between the three groups (p=0.289). Adjusting for potential confounders did not significantly alter these results. When relative decline in serum CA125 levels were cross- tabulated with surgical outcome, a significant trend towards greater declines in those with a better surgical outcome was found (p=0.035).
Table 4: Distribution of patients according to perioperative relative change in CA125 levels and the amount of residual tumor.

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Most of the patients (65.89%) were of serous cystadenocarcinoma and in all these patients CA125 level were raised. Poorly differentiated carcinoma , papillary adenocarcinoma and endometroid adenocarcinoma were also found and they all had raised CA125 level. In 96.53 % cases we found raised CA125. This implies the importance of CA 125 in the diagnosis of ovarian cancer with higher sensitivity.

Most of the patients (53.75%) were of higher stage (III/IV) out of these 95.7% patients had CA125>500. [Table 3] Distribution of patients according to resectability of mass and serum CA125
Table 3: Distribution of patients according to resectability of mass and serum CA125

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[Table 2] and [Table 3] showed that CA125 level can predict the stage of cancer and also resectability of tumour prior to operation (p 0.0067).
Table 1: Distribution of ovarian mass patients having abnormal CA125 level according to their histopathology

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Table 2: Showed rela onship between severity of abnormal level CA125 and stage of ovarian cancer (OC)

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  Discussion: Top


In the study perioperative changes in serum CA125 level is an early biomarker for predicting disease-specific survival in patients that have undergone cytoreductive surgery. After controlling for known prognostic factors, the relationship between changes in perioperative serum CA125 levels and disease-specific survival had greater prognostic value than the level of residual disease after primary surgery.

These findings are in agreement with those reported by others. Yoo et al.[12] reported that a ≥75% decline in serum CA125 levels was an independent prognostic factor for progression-free survival. Zivanovic et al.[13] combined the decline of serum CA125 with the result of debulking surgery and showed that optimally debulked patients in the “high decline” group (≥80% reduction in CA125 levels) were at lower risk of recurrence than patients with a smaller decline. The multivariate analysis performed by Zivanovic et al.[13] also showed that disease-specific survival had greater prognostic value than the level of residual disease after primary surgery, although they placed little emphasis on this in their report.

Our study confirmed the results of previous reports showing that the outcome of debulking surgery is correlated with disease specific survival.[6],[7] Complete debulking surgery showed an improved disease specific survival when compared to inadequate debulking (p=0.003). Although not significant, optimal debulking was also related to improved survival (p=0.201) when compared to inadequate debulking. When correlating the changes in perioperative CA125 levels and the outcome of surgery, we found a linear association between the categories of relative perioperative CA125 decline and the outcome of surgery (p=0.035).

The present study has several limitations. The first is its retrospective nature. A second is that number of patients included in the study was less. A third is that some patients was excluded due to a lack of data regarding CA125 levels. A fourth is that serum CA125 levels were measured in different postoperative weeks (range 0-5 weeks), which may have influenced the rate of postoperative decline.

Indeed, the peritoneum normally forms a barrier to CA125 transport, and incision of the peritoneum leads to the release of CA125 into the peritoneal fluid. Thus, peritoneal trauma may cause CA125 release, and manipulation of the tumor during surgery may lead to increased shedding of CA125 into the circulation as remaining barriers between tumor and surrounding tissue are disturbed. The removal of tumors and ascites from patients with ovarian cancer leads to a reduction in serum CA125 levels, whereas peritoneal trauma caused by the surgical procedure does the opposite.[4] Evidence suggests that postoperative CA125 levels increase after incision and healing of the peritoneum via de novo synthesis.[14] This increase may mask any decline in perioperative CA125 levels after the removal of tumor tissue and ultimately cause an increase in serum postoperative CA125 levels.

CA125 is not the best prognostic variable, but it remains an important marker in managing the diagnosis, treatment and follow up of epithelial ovarian cancer patients (EOC). Our study suggested that perioperative decline of CA125 level was the most significant prognostic factor for predicting progress - free survival and overall survival in advanced EOC. It is important for follow up of EOC.
  Conclusion: Top


Volume of residual tumor after debulking is known as the most important prognostic factor for survival, but its intraoperative assessment is subjective. We have identified a relationship between the perioperative relative change in CA125 levels and the amount of residual tumor remaining after primary cytoreductive surgery. Less residual tumor was associated with a greater relative decline in serum CA125 levels. Perioperative changes in serum CA125 levels were also associated with disease-specific survival and were a stronger predictor than the estimated amount of cytoreduction at surgery. A decline of ≥80% resulted in an almost 4-fold increase in survival to all patients with advanced stage epithelial ovarian cancer.

The current retrospective study suggests that the preoperative CA125 value determines the resectability of ovarian mass and also post operative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent cytoreductive surgery for EOC.



 
  References Top

1.
WHO. Global health observatory data repository. Number of deaths: world by cause.2014.  Back to cited text no. 1
    
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.  Back to cited text no. 2
    
3.
Baldwin LA, Huang B, Miller RW, Tucker T, Goodrich ST, Podzielinski I, et al. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol. 2012;120:612-618.  Back to cited text no. 3
    
4.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29.  Back to cited text no. 4
    
5.
Soletormos G, Duffy MJ, Othman Abu Hassan S, Verheijen RH, Tholander B, Bast RC, Jr, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European group on tumor markers. Int J Gynecol Cancer. 2016;26:43-51.  Back to cited text no. 5
    
6.
Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev. 2011;(8):CD007565.  Back to cited text no. 6
    
7.
Chang SJ, Bristow RE. Evolution of surgical treatment paradigms for advanced-stage ovarian cancer: redefining ‘optimal’ residual disease. GynecolOncol. 2012;125:483-492.  Back to cited text no. 7
    
8.
Salani R, Backes FJ, Fung MF, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204(6);466-478.  Back to cited text no. 8
    
9.
Morgan RJ, Alvarez RD, Armstrong DK, et al. Ovarian Cancer, version 2.2013. J NatlComprCancNetw. 2013;11:1199-1209.  Back to cited text no. 9
    
10.
Armstrong A, Otvos B, Singh S, Debernardo R. Evaluation of the cost of CA-125 measurement, physical exam, and imaging in the diagnosis of recurrent ovarian cancer. GynecolOncol. 2013;131:503- 507.  Back to cited text no. 10
    
11.
Ramsey SD, Ganz PA, Shankaran V, et al. Addressing the American healthcare cost crisis: role of the oncology community. J Natl Cancer Inst. 2013;105(23):1777-1781.  Back to cited text no. 11
    
12.
Yoo SC, Yoon JH, Lyu MO, Kim WY, Chang SJ, Chang KH, et al. Significance of postoperative CA-125 decline after cytoreductive surgery in stage IIIC/IV ovarian cancer. J Gynecol Oncol. 2008;19:169-172.  Back to cited text no. 12
    
13.
Zivanovic O, Sima CS, Iasonos A, Bell-McGuinn KM, Sabbatini PJ, Leitao MM, et al. Exploratory analysis of serum CA-125 response to surgery and the risk of relapse in patients with FIGO stage IIIC ovarian cancer. Gynecol Oncol. 2009;115:209-214.  Back to cited text no. 13
    
14.
Pelissier A, Bonneau C, Chereau E. et al. CA125 kinetic parameters predict optimal cytoreduction in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy. Gynecol Oncol. 2014; 135(3);542-6.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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