**2. Clinics and diagnosis**

inexistence of an effective screening method and to the aggressive biology of this tumor with

The geographic variability in OC incidence is considerable, being frankly higher in developed countries with rates surpassing 7.5/100,000 women. The highest continental rate is registered in Europe, where 65,584 new OC cases were observed. In opposite, the lowest continental values were registered in African regions, with incidence rates below 5/100,000 women [1]. Concerning mortality, for women with less than 75 years, the average risk of dying from OC is twice as high in more than less-developed regions. Inclusively, for developed countries, OC stands as the fifth most lethal cancer among women [1]. In Europe, in 2012, 42,749 deaths were observed, which corresponds to more than 25% of all worldwide OC deaths [3, 4]. Among the gynecological tumors, OC is the leading cause of death even being only the third most com-

Nevertheless, the numerous attempts to characterize the ovarian carcinogenesis and etiology, age is considered as a major determinant for OC development: there is an increased disease

Beyond age, an important risk factor for OC is the familiar history. Although the germline mutations in genes that predispose to OC are relatively rare in the general population, they are responsible for approximately 10–20% of all cases [6, 7]. The critical genes involved in hereditary OC are *BRCA1* and *BRCA2*, associated with hereditary breast/ovarian cancer syndrome. The risk of spontaneous OC development, throughout life, is around 1.7%, while the heritage of germline mutations that alter *BRCA1* gene function confers a cumulative risk from 40 to 60%, mainly to serous carcinoma. The presence of pathogenic mutations in *BRCA2* gene lowers the risk for about a half (10–30%). OC hereditary women tend to develop the disease

Moreover, reproductive and endocrine factors seem to be important, whereby the nulliparity, early menarche (<12 years), late menopause (>52 years), endometriosis, polycystic ovary syndrome, and the recent exposure to hormone replacement treatment might be associated with a higher risk to develop OC [11–14]. Therefore, some behaviors and lifestyles were associated with a decrease in OC incidence, namely breastfeeding, multiparity, and the oral contraceptives use [11, 13]. Surgical procedures such as tubal ligation, hysterectomy with salpingectomy, and oophorectomy correlate with a lower incidence of this tumor but are mainly reserved for women with higher disease risk, after the completion of familiar

Standard treatment of epithelial ovarian cancer (EOC) is based on cytoreductive surgery, followed by platinum-based first-line chemotherapy. This neoplasia is considered chemosensitive, yielding 40–60% of complete responses rates for advanced disease stages. Despite the apparent efficacy of treatment, up to 75% of patients will relapse and become candidates for second-line chemotherapy. As a result, the high percentage of late-stage diagnosis and the occurrence of tumor recurrence limit the treatment efficacy, and the overall 5-year survival

In the clinical practice, several pathological factors are considered prognostic for EOC patients, and many efforts are made to identify those that will improve patient's stratification and be

the ability to disseminate.

58 Ovarian Cancer - From Pathogenesis to Treatment

planning.

rate remains only around 45%.

mon, preceded by cervical and endometrial cancers [2–4].

risk after the menopause, being 63 the median age at diagnosis [5].

nearly 10 years earlier than women with sporadic OC [8–10].

Upon the detection of an adnexal mass suspected of malignancy, the diagnostic approach should be based on a careful clinical history that should include the overall physical examination, as well as gynecological, rectal, and abdominal evaluation. After the clinical evaluation, additional diagnostic and biochemical tests should be requested, judiciously and objectively, to aid in the differential diagnosis of a pelvic mass. Among the complementary diagnostic tests, transvaginal ultrasonography (TVU) and CA125 tumor marker determination are mandatory [8, 12, 15]. Other markers are also used in the diagnostic investigation for suspected EOC cases, such as CEA and CA19.9.

In the suspicion of ovarian neoplasia, abdominal-pelvic computed tomography (CT) should be requested to confirm and characterize the presence of lesions, to evaluate the tumor extension, to identify unresectable disease, and to exclude nonovarian metastatic disease. Nevertheless, the EOC diagnosis is surgical as only the anatomopathological exam confirms the definitive diagnosis. Diagnostic radiologically guided aspiration/biopsy or laparoscopy should be requested, whenever neoadjuvant chemotherapy is being considered [8, 16].

Late disease diagnosis explains, in part, the high mortality rate of these patients [12, 17]. Over the past 25 years, there has been little improvement in the survival rate, being around 37% in the early 1970 and 44% in 2000, despite the advances in the medical treatment [18]. However, the currently available tests lack adequate sensitivity and specificity, promoting a noneffective screening strategy. Prospective studies have shown that the combined use of serum CA125 and TVU improved the specificity of the tests and allowed the detection of a number of OC cases in the preclinical phase (this is discussed in detail in another chapter).
