Pre-op Diagnosis of Ovarian Cancer in Patients Presented with Adnexal Mass

Objective: 
To detect ovarian cancer in patients presented with adnexal mass using Risk of Malignancy Index (RMI) based on menopausal status, ultrasound findings and serum level of CA125.

Design: 
Prospective study

Setting: 
Al-Hussein University Hospital, Cairo-Egypt

Participants: 
One hundred and forty women, 30 years or older, admitted with adnexal mass between September 1998 and February 2002, for laparotomy.

Main Outcome Measures: 
The sensitivity, specificity and positive predictive value of RMI based on menopausal status, ultrasound findings and CA125 to diagnose ovarian cancer patients.

Results: 
Using a cut-off level of 190 to indicate malignancy, the RMI gave sensitivity of 86.67 %, specificity of 92.5 % and positive predictive value of 89.66 %.

Conclusion: 
The risk of malignancy index is able to correctly discriminate between malignant and benign adnexal mass. It is highly recommended to be introduced into clinical practice in Egypt to facilitate the selection of patients for primary surgery at an Gynecologic Oncology Unit.

Introduction:
Adnexal mass can represent a number of different benign and malignant conditions. Laparotomy is essential to establish the nature of adnexal mass. Ovarian cancer is the most lethal of genital malignancy and surgical staging is recommended by FIGO. Proper staging is the key to an accurate prognosis.(1) The amount of residual malignant tissue after primary surgery is among the best prognostic factors in ovarian cancer (2-4), however, many patients do not receive appropriate surgery at the time of surgical diagnosis (5, young).

The greatest opportunity to influence the natural history of ovarian cancer occurs at the initial laparotomy. Therefore, patients with ovarian malignancy should be referred to a special center for gynecologic oncology.

In practice, the diagnosis of ovarian cancer is often difficult to make preoperatively and inadequate surgical exploration by junior or inexperienced surgeon is a regular occurrence.  Sensitive and specific method for preoperative diagnosis of ovarian cancer would provide a rational basis for referral before diagnostic laparotomy. Patients with ovarian malignancy would thereby be ensured of the benefits of thorough surgical staging and cytoreduction by an experienced surgeon.

A method for better preoperative discrimination of patients with adnexal mass was introduced by Jacob et al (6)(RMI) based on the menopausal status, ultrasound findings and serum level of CA125, where, RMI=M X U X CA125, (M= menopausal status, U= Ultrasound score and CA125). This method was evaluated by others (7-9).

The purpose of this study was to apply RMI for patients presented with adnexal mass to examine the sensitivity, specificity and positive predictive value of the Risk of Malignancy Index in identifying patients with ovarian cancer among Egyptian women presented at Al-Hussein University Hospital, Cairo-Egypt.

Methods:  
Hundred forty patients with adnexal mass were eligible for this study between February 1997 and February 2002.

Preoperative serum CA125 level (IMX, Abbott Laboratories, USA), ultrasound findings and menopausal status were registered.

Ultrasound examination was performed vaginally using 6.5MHz transducer (Medison, Korea) and extended transabdominally when needed with 3.5 MHz transducer.

The presence of bilateral lesions, a multilocular cystic lesion, solid areas, ascites and intraabdominal metastases were reported. 

Postmenopausal status was defined as more than one year of amenorrhoea or age older than 50 years in women who had had a hysterectomy. Patients who did not meet these criteria were classified as premenopausal.

Based on the data obtained the Risk of Malignancy Index was calculated for each patient.

The calculation was based on a simple regression equation where total ultrasound score of 0 or 1 gave U=1 and a score >2 gave U=3.

Premenopausal status gave M=1 and postmenopausal M=2.

The serum level of CA125 was applied directly into the calculation and Risk of Malignancy Index was calculated as follows: RMI = U X M X CA125.

All statistical analysis was done in statistical package for social science, SPPS inc. version 5.1.

Chi-square tests were used to test difference in distribution of age, menopausal status and ultrasound score. The Man-Whitney U test was applied when testing differences in distribution of CA125 among women with benign and malignant adnexal mass. 

Sensitivity, Specificity, Positive Predictive value (PPV) and Negative predictive value (NPV) was calculated for CA125 and RMI in diagnosis of ovarian cancer.

Results: 
Out of 140 patients presented with adnexal mass, 60 (%) had malignant disease and 80 (%) benign pathology.

Benign Gynecological conditions included: functional cysts (n=30), simple serous cyst (n=16), Dermoid cyst (n=10), tubo-ovarian abscess (n=5), Endometriosis (n=8), Broad ligament fibroma (n=3), Hydrosalpinx (n=3), Mucinous cystadenoma (n=3),Ovarian fibroma (n=1) and tubercloma (n=1).  

Malignant tumors were: Serous cystadenocarcinoma (n=26), Mucinous cystadenocarcinoma (n=20), Endometrial adenocarcinoma (n=4), Borderline mucinous adenocarcinoma (n=2), Undifferentiated carcinoma (n=5), metastatic breast carcinoma (n=3).

Statistically significant differences were found between the groups with benign and malignant pathology as far as age, menopausal status, ultrasound score and serum level of CA125 were concerned (table 1). Distribution of patients according to CA125 levels and MRI is shown in figures 1 and 2.

Sensitivity, specificity, positive predictive value and negative predictive value for CA125 and RMI are shown in table 2.

The best performance was obtained for serum CA125 level of 55 U/ml (sensitivity96.67 %, specificity 96.77 % and PPV 96.77 %) and for RMI a cut-off value of 190 gave the best performance with sensitivity of 86.67 %, specificity of 92.5 % and PPV of 89.66%.  The performance of CA125 and RMI is shown in the receiver-operator characteristic curve (figure3).

Discussion:
The accuracy of diagnostic tests used to evaluate an adnexal mass is of great concern to practicing gynecologists. In the pre-operative assessment of adnexal mass, the major diagnostic tools are still clinical impression and ultrasound examination. However, due to limitation of clinical impression and sonographic finding to predict ovarian malignancy, it is not surprising that gynecologists may detect an unsuspected ovarian malignancy intraoperatively. Often an improper incision is made, the bowel is not adequately prepared or the surgeon is confronted with the need to perform an unplanned cytoredctive surgery.

A scoring system that predict ovarian malignancy can improve the chance of better preoperative counseling, better preoperative preparation and where appropriate referring the patients to a specialized center.

Subsequent to introduction of RMI (6) the same research group had re-evaluated their diagnostic method in a new group of patients admitted for pelvic masses and confirmed the sensitivity and specificity of RMI and its priority compared to the individual criteria (7).

In this study menopausal status had a sensitivity of 71% and specificity of 87% while ultrasound score had a sensitivity of 70% and specificity of 82%. The serum levels of CA125 were similar to those reported in other studies in differentiation between benign and malignant ovarian mass (21,22).

The main limit of CA125 is that it may be high in benign disease such as ovarian cysts, endometriosis and pelvic infection. The combination of serum CA125 with menopausal status (22), other tumor markers (15) and ultrasound parameters (23) increases the discriminating power of the method for the two types of ovarian pathology.

The RMI developed by Jacobs et al (6) for distinguishing benign and malignant pelvic masses pre-operatively at a cut-off level of 200 had a sensitivity of 85.4% and a specificity of 96.9%, Davis et al (7) found a sensitivity of 87% and specificity of 89% for this index. In this study RMI at a cut-off 190 gave sensitivity of % and specificity of %, however, Tingulstad et al (8) found a sensitivity of 71% and specificity of 96% for This RMI and found a sensitivity of 80% and specificity of 92% for their RMI2 at cut-off level of 200, also Mogante et al (9) found a sensitivity of 81% and specificity of 90% using their RMI2 with cut-off level of 125.

At lower cut off values the sensitivity increases at the expense of specificity, while at a higher cut off values the specificity increases at the expense of sensitivity and more benign cases will be referred as malignant. So the decision of the cut off value (action line) will balance the sensitivity and specificity on one side and the local resources and availability of the specialists on the other side. When there is limitation of referral for specialist care because of distant resources, the RMI can be increased with some degree of sacrifices in sensitivity to achieve a higher level of specificity.

Conclusion: 
The risk of malignancy index provides a quantitative assessment of the risk of malignancy and can be used to discriminate between benign and malignant disease. Its application in clinical practice would provide a rational basis for specialist referral of patients with malignant disease before diagnostic surgery.

Table 1
Distribution of age, menopausal status, ultrasound score and serum CA125 in 140 women with benign (n=80) and malignant (n=60) adnexal mass.
Values are given as n (%)

30-44

45-55

>55

35 (43.75)

38 (47.5%)

7 (8.75%)

3 (5%)

18 (30%)

39 (65%)

X 2

X 2

X 2

<0.001*

Premenopause

Postmenopause

62 (77.5)

18(22.5)

18 (30)

42 (70)

X 2

X 2

<0.003*

1

3

74 (92.5)

6 (7.5)

12 (20)

48 (80)

X 2

X 2

<0.001*

Minimum

Maximum

Mean

8

161

29.7

24

752

357

U test

<0.001*

*Significant

Table 2
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CA125 levels and RMI

30
35
40
50
55
160

100
96.77
96.67
96.67
96.7
86.7

83.87
90
93.55
93.55
96.77
96.77

85.71
90.91
93.55
93.55
96.67
96.3

100
96.43
96.67
96.67
96.67
88.24

91.8
93.44
95.08
95.08
96.77
91.8

30
35
40
50
70
80
160
190
230

100
96.67
96.67
93.33
90
86.67
86.67
86.67
66.67

70
75
80
82.5
85
87.5
90
92.5
100

71.43
74.36
78.38
80
81.82
83.87
86.67
89.66
100

100
96.7
96.97
94.29
91.89
89.74
90
90.24
80

82.86
84.29
87.14
87.14
87.14
87.14
88.57
90
85.71

Figure 1 Distribution of CA125 among benign and malignant cases.

Figure 2 Distribution of RMI among benign and malignant cases

Figure 3. Receiver operator characteristics curve of CA125 and RMI in discrimination between benign and malignant adnexal mass

References:

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