CA 125 levels in the preoperative assessment of advanced-stage uterine cancer

doi:10.1067/mob.2003.304

American Journal of Obstetrics and Gynecology

Volume 188, Issue 5, May 2003, Pages 1195-1197

https://doi.org/10.1067/mob.2003.304 Get rights and content

Abstract

Objective: The purpose of this study was too evaluate preoperative levels of CA 125 in for the prediction of advanced uterine cancer. Study Design: We conducted a retrospective analysis of the correlation of preoperative CA 125 with grade, depth of invasion, lymph vascular space involvement, lymph node status, and stage. Results: High CA 125 levels correlated with advanced-stage (P <.0001) and positive (P <.0001) lymph node status. High levels of CA 125 also correlated with the deepest myometrial invasion, the presence of lymph vascular space involvement, and the highest grade. Receiver-operator characteristic curves demonstrated that depth of invasion, lymph vascular space involvement, and grade accurately predicted advanced-stage disease 73%, 77% and 80% of the time, respectively. CA 125 levels, however, correctly predicted advanced stage 94% of the time. The sensitivity and specificity of a CA 125 cutoff level of 37 IU/mL were 95% and 90%, respectively, with a positive predictive value of 78% and a negative predictive value of 97%. Conclusion: CA 125 appears to be a significant independent predictor of positive lymph node status and the extrauterine spread of disease. (Am J Obstet Gynecol 2003;188:1195-7.)

Section snippets

Methods

This study was conducted as a retrospective chart review of patients who were treated for primary uterine cancer in the Division of Gynecologic Oncology at Westchester Medical Center. We identified those patients who had CA 125 levels drawn as part of their preoperative evaluation and who were treated between June 2000 and March 2002. All patients underwent surgical staging, which included pelvic and para-aortic lymphadenectomy. International Federation of Gynecologists and Obstetricians stage

Results

There were a total of 65 patients. The median age was 61 years. CA 125 levels ranged from 3.6 IU/mL to 1077.1 IU/mL (median, 173 IU/mL). The distribution of patients according to stage was as follows: stage I, 40 patients; stage II, 6 patients; stage III, 14 patients; and stage IV, 5 patients.

Higher CA 125 levels correlated with advanced stage (P <.0001). The mean CA 125 level in the early stage (I and II) was 42.7 IU/mL; the mean CA 125 level in the advanced stage (III and IV) was 346.9 IU/mL

Comment

The use of grade, depth of myometrial invasion, and LVSI in the determination of the need for pelvic and para-aortic lymphadenectomy had been well documented. Creasman et al¹ demonstrated that, in the presence of the highest grade and the deepest myometrial invasion, pelvic lymph node metastases were predicted only 34% of the time.

The performance of an intraoperative lymph node evaluation depends on the presence of such criteria as grade 3 lesions, grade 2 tumors that are >2 cm in diameter,

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Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma
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Elevations of CA-125 were first described in patients with recurrent and advanced endometrial cancer by Niloff et al. [11] in 1984. A number of studies have since shown that elevated pre-operative serum CA-125 correlate with extra-uterine tumor spread [12–15]. Furthermore, patients with pre-operative serum CA-125 elevation showed reduced actuarial survival in at least one study [16].
To evaluate the usefulness of pre-operative serum CA-125 in the management of women diagnosed with uterine papillary serous carcinoma (UPSC). We hypothesized that elevated pre-operative levels of serum CA-125 correlate with higher disease stage and poorer prognosis.
Patients diagnosed with UPSC and managed in our institution were identified over a period of 10 years, 1995 to 2005. All required information were extracted from their records. The nonparametric test applied for comparison of data included Kruskal Wallis H-test and Man–Whitney U-test. The χ² test and Spearman correlation test were used to examine the association of serum CA-125 with different parameters. Receiver operator characteristic curves (ROC) were used to quantify marker performance. Recurrence and survival were analyzed using Kaplan–Meier method. Multivariate analyses were performed with a Cox proportional regression method.
A total of 41 patients met the study criteria. Mean pre-operative serum CA-125 levels were significantly higher in patients with stage IV (1150 ± 1297 U/mL), compared with stage III (181 ± 232 U/mL; P < 0.001), stage II (22 ± 9; P < 0.001), and stage I (14 ± 1; P < 0.001). CA-125 correlated strongly with stage (r = 0.68, P < 0.001). On the ROC, a cut-off of 35 IU/mL provided the best sensitivity and specificity (78% vs. 100% respectively) for extra-uterine disease. Disease free survival (DFS) and overall survival (OS) were longer in patients with CA-125 < 35 U/mL compared with CA-125 ≥ 35 U/mL [median DFS not reached during study vs. 21.2 months (P = 0.009), and median OS not reached during study vs. 25 months, (P = 0.0001) respectively]. Multivariate regression model showed CA-125 as the only variable associated with survival (P = 0.05).
Pre-operative serum CA-125 levels correlate with stage of disease in patients with UPSC. This may be important for management planning, prognostication and counseling in these women.
Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus
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The most commonly used tumor marker as an aid in the clinical management of endometrial cancer is CA125. A number of studies involving patients with uterine cancer have shown that serum CA125 levels correlated with advanced stage disease and with the presence of extrauterine disease, such as lymphatic and peritoneal metastases [8,21]. Another study reports that only 10% of patients with stages I and II disease have elevated CA125 levels [22].
Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus.
Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%.
Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125.
HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.
Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma
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More recently, the potential utility of CA125 measurement has been evaluated in endometrial cancer patients. Several investigators have found that preoperative CA125 elevation in endometrial cancer patients is associated with pathologic risk factors such as high grade, deep myometrial invasion, lymphovascular involvement, extra-uterine disease, and nodal metastases [18–23]. In addition, preoperative CA125 elevation is associated with reduced actuarial survival in at least one study [24].
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Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate the relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of the prognostic factors identified by univariate analysis.
Preoperative CA125 was significantly associated with the presence of extrauterine disease (P < 0.001), deep myometrial invasion (P < 0.001), and serous histology of the epithelial component (P = 0.005). Using univariate survival analysis, stage (HR = 1.808, P = 0.004), postoperative CA125 level (HR = 9.855, P < 0.001), and estrogen receptor positivity (HR = 0.314, P = 0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR = 5.725, P = 0.009).
Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS.
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^☆: Reprint requests: Helen Jhang, MD, University OB/GYN, PC, 19 Bradhurst Ave, Suite 2700, Hawthorne, NY 10532.

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Residents' Papers GynecologyCA 125 levels in the preoperative assessment of advanced-stage uterine cancer☆

Abstract

Section snippets

Methods

Results

Comment

Gynecol Oncol

Gynecol Oncol

Am J Obstet Gynecol

Surgical pathologic spread patterns of endometrial cancer: a Gynecologic Oncology Group study

Cancer

Preoperative selection of patients with low stage endometrial cancer at high risk for pelvic lymph node metastases

Int J Gynecol Cancer

Residents' Papers Gynecology
CA 125 levels in the preoperative assessment of advanced-stage uterine cancer☆