RISK OF MALIGNANCY INDEX IN PREOPERATIVE EVALUATION OF CLINICALLY RESTRICTED OVARIAN CANCER

Ovarian cancer remains the third most frequent gynecological neoplasm and corresponds to the highest mortality rate in developed countries. In Brazil, according to Datasus files, the incidence of malignant ovarian tumors was reported to be 3.6 per 100,000 women in 1998, resulting in 1830 deaths in the same year. A worse prognosis is correlated with late diagnosis. Up to 70% of the cases are detected at advanced stages, with increased ovarian disease, in which the mortality rate reaches 70% within two years and 90% within five years, which has encouraged research into ovarian cancer screening methods.

Ovarian tumors are presented as adnexal masses which give rise to a number of different benign and malignant conditions. The accurate diagnosis of an adnexal mass is a challenge for the gynecologist, because of its bizarre and atypical behaviour.

Preoperative diagnostic procedures that are able to distinguish whether an ovarian neoplasm is malignant or benign, could be useful in planning optimized treatment. Until now, the standard strategy for differential diagnosis has been exploratory laparotomy. On the other hand, detailed analysis of the origin of the pelvic mass has encouraged the use of minimal invasive surgery, such as laparoscopy or mini-laparotomy, in selected cases a preoperative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic masses to an oncological unit for appropriate therapy and optimized debulking.

Several diagnostic methods for pelvic masses have been reported, such as abdominal and transvaginal ultrasonography, three-dimensional ultrasound, color Doppler ultrasonography and tumor markers However, none of these methods used individually has shown significantly better performance in detecting malignant tumors from clinically restricted ovarian masses. The development of a mathematical formula using a logistic model, incorporating menopausal status, the serum level of a glycoprotein called CA 125 (which is considered to be a tumor marker) and ultrasound findings in a score system, has been described in the literature in the form of different malignancy indexes. These indexes were calculated using a simplified regression equation obtained from the product of the ultrasound findings score, the menopausal status score and the absolute value of CA 125 serum levels. Jacobs et al. originally developed the risk-of-malignancy index in 1990 and it is termed the risk-of-malignancy index #1. Tingulstad et al. developed a risk-ofmalignancy index in 1996, known as risk-of malignancy index #2 and in 1999 they modified it to form the risk-of-malignancy index #3. The difference between the three indices lies in the different scorings of ultrasound findings and menopausal status.14-16 All indices presented a significantly better performance in diagnosing malignancy than did each predictor taken separately. These indices were tested by Morgante et al.18 on another population with evident malignant criteria in the ultrasonography, such as hepatic or distant metastasis, and they found that the risk-of-malignancy index #2 performed better for detecting ovarian malignancy.

In women without evidence of advanced stage ovarian cancer, the current risk-of malignancy index is useful in clinical practice for differentiating malignant from benign pelvic masses, as compared to each individual component measured separately. In the present population, this index was more accurate in comparison with the best individual predictor and CA 125 serum level. No increase in the accuracy was observed when analyzing patients' ages, tumor measurements or bilaterally. The validity of the index depends on the proportions of malignant neoplasm and benign processes and the proportions of initial and advanced stages.

Although the previous indices were applied to cases in more advanced stages, quite possibly the best application for the index could be for those cases without ultrasonographic evidence of malignancy. This occurs because the risk-of-malignancy index system translates the morphological description of pelvic mass into objective numerical data, reducing the bias attributable to the examiner's subjectivity. The recent development of ultrasound techniques and the better characterization of malignant masses by this method have led to better performance by ultrasound as a predictor of malignancy, especially in those cases with hepatic, intraabdominal or neighboring organ metastases. Ascites associated with pelvic masses is a recognized sign of malignancy. Some cases of rare non-neoplastic conditions are also associated with ascites. Despite this, no association was found between ascites and malignancy in this study, in a univariate analysis.

In the present study, the malignant ovarian neoplasm group consisted mainly of early invasive or borderline tumors (67%). Among the advanced tumors, the majority of the stage III cases were so classified due to lymph node invasion. None of the cases presented clear preoperative evidence of metastasis. Borderline tumors and benign processes can be treated in a general hospital by gynecologists, although invasive neoplasia, particularly advanced invasive cases, merits appropriate therapy by highly skilled surgical teams in specific oncology centers. The risk-of-malignancy index facilitates the selection of cases for referral to an oncological unit and also helps the surgeon to choose the surgical approach. For example: a premenopausal 35-year-old woman with a solid well-defined wall tumor and a CA 125 serum level of 45 U/ml presents a risk-of-malignancy index of 45. At the cut-off point of 150, the tumor can be considered as benign and the false-negative probability is around 21%.

However, the probability at the cut-off point of 100 is 16%. A tumor with the same characteristics, in a postmenopausal 65-year-old woman, with a CA 125 level of 97 U/ml has a risk-of-malignancy index of 291. At the cutoff point of 150, this tumor can be considered as malignant with a false-positive probability of around 21%, and at the cut-off point of 200 this tumor is still considered as malignant, with

a false-positive probability of 14%.

CONCLUSION

In conclusion, the risk-of- malignancy index is apparently able to identify the probability of malignant pelvic masses, by incorporating serum CA 125 serum levels, ultrasound morphology and menopausal status, performed individually in women with ovarian masses. The main purpose of this study was the evaluation of a risk-of-malignancy index defined in a selected population of apparently early lesions. This index is a simple score system which can be applied directly to clinical practice and might be of value in the preoperative assessment of the adnexal mass.

It showed itself useful in referring patients with advanced neoplasia to a more complex healthcare unit, although it does not seem to show prognostic value. However, the performance of the present index must be evaluated in other studies, using a validation sample from a similar population.

REFFERENCE

1.      Jose Carlos CT, Sophie Francois MD, Anibal Faundes, et. al. 2002. Risk-of-Malignancy Index  in preoperative evaluation of clinically restricted ovarian cancer. Sao Paolo Med J/Rev Pau Med 2002; 120(3): 72-6

2.      Surawute L, Siriwan T, Sumonmal M, et. al. 2005. Comparison of Ultrasound score, CA 125, Menopausal Status, and Risk of Malignancy Index in Differentiating between benigna and Borderline or Malignant Ovarian Tumors. J Med Assoc Thai Vol. 88 Suppll. 2 2005