Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma

doi:10.1016/j.ygyno.2008.05.027

Gynecologic Oncology

Volume 110, Issue 3, September 2008, Pages 293-298

https://doi.org/10.1016/j.ygyno.2008.05.027 Get rights and content

Abstract

Objective

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.

Methods

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.

Results

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).

Conclusion

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.

Introduction

Uterine papillary serous carcinoma (UPSC) is an aggressive endometrial neoplasm that resembles ovarian serous carcinoma morphologically; the tumor has complex papillary architecture, is accompanied by marked nuclear atypia and psammoma bodies may be present in approximately 60% of cases. It represents less than 10% of endometrial carcinomas but accounts for over 50% of all relapses and deaths caused by this disease [1], [2], [3]. Unlike typical endometrioid adenocarcinomas of the endometrium, these tumors have a higher propensity for lymphovascular space invasion, and present frequently with involvement of cervical tissue, broad ligament, fallopian tubes, ovaries, peritoneal surfaces of the pelvis and abdomen, metastasis to the liver, brain, and skin [3]; mimicking the usual distribution of ovarian papillary serous cancer. Patients with UPSC have a poor 5-year overall survival of only 18–27% [4], [5]. At the time of presentation, approximately 60 to 70% of women with UPSC will have disease spread outside of the uterus [3], [6], and even in cases apparently confined to the uterus, 31–80% of patients develop recurrent disease [7]. Survival of patients with stages I–II UPSC (35–50%), is remarkably different from those patients with stages III–IV disease, 0–15% [8]. A test that distinguishes between these stages will help in management planning, prognostication and counseling.

The tumor-associated antigen CA-125 has played a role in monitoring of treatment, detection of recurrence and as a prognostic marker in women with epithelial ovarian carcinoma [9], [10]. 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], [13], [14], [15]. Furthermore, patients with pre-operative serum CA-125 elevation showed reduced actuarial survival in at least one study [16]. However, all these studies included different types of histology. To our knowledge, none of the previous studies in the literature have evaluated the potential clinical implications of pre-operative serum CA-125 solely in patients diagnosed with UPSC.

We hypothesized that pre-operative serum CA-125 levels would correlate with disease stage and have an impact on prognosis in patients diagnosed with UPSC.

Section snippets

Patients and methods

Between January 1995 and December 2005, 54 patients with a histologically verified USPC were identified from our Cancer Registry database who have had primary surgery at our institution. In every case, the surgery was performed by a gynecologic oncologist. Staging surgery was in accordance with FIGO adopted system and included peritoneal washing for cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy. This study was approved by our

Results

The demographic and histopathologic characteristics of the 41 patients who were included in the final analysis are presented in Table 1. Ages ranged from 46 to 87 years, with a median age of 68 years. Of the 41 patients, 12 (29.3%) had stage I disease, 2 (4.9%) had stage II disease, 15 (36.5%) had stage III disease and 12 (29.3%) had stage IV disease. Fourteen percent of the tumors were grade 1, 46% grade 2 and 39% grade 3. Complete surgical staging including washing cytology, total abdominal

Discussion

The tumor antigen, CA-125, was first introduced by Bast in 1981 [17]. Since then, it has been evaluated for ovarian cancer screening [18], [19], [20], diagnosis [21], [22], [23], and post-treatment monitoring [24], [25], [26], [27]. The current body of literature does not support the use of CA-125 as a screening tool for ovarian cancer in routine populations but it helps in diagnosis and has become an established method of monitoring response to treatment, as well as disease

Conflict of interest statement

The authors have no conflicts of interest to declare.

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Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients and methods

Results

Discussion

Conflict of interest statement

Gynecol. Oncol.

Best Pract Res

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Ann Oncol

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Obstet. Gynecol.

J. Clin. Epidemiol.

Ann Oncol

Am. J. Obstet. Gynecol.

Gynecol. Oncol.

Am. J. Obstet. Gynecol.

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol Oncol

Mod Pathol