**3. Histopathology**

Ovarian tumors are classified according to the World Health Organization (WHO) proposal for gynecological tumors. Ovarian cancer has high cellular heterogeneity, and most of the primary ovarian tumors can be integrated into three major groups, namely epithelial, sex cord and ovarian stroma, and germ cell tumors [2].

Although the ovarian epithelial surface represents only a small fraction of all ovarian cell types, EOC is the most common, corresponding to almost 60% of all ovarian tumors [19, 20]. According to the criteria proposed by the WHO in 2014, EOC can be divided into seven histological subcategories, namely serous, mucinous, endometrioid, clear cell, Brenner, seromucinous, and undifferentiated [2]. All the mentioned histological subtypes, except for the undifferentiated type, are further subdivided into benign, borderline, and malignant neoplasia, depending on the optical microscopy characteristics.

Sex cord and stroma tumors arise from the ovarian connective tissue, often responsible for hormone secretion. These tumors encompass a vast group of tumors, for which the subgroup of "pure" ovarian stromal tumor is the most frequent (9% of all OC), usually with benign behavior. Also in this group of tumors, granulosa cell tumors are associated with aggressive behavior and represent 1% of all OC. Regarding the germ subgroup, a mature cystic teratoma is very common (32% of all OC), although the remaining germ cell tumors, both benign and malignant, are rare, representing 3–5% of all OC cases [2, 21].

is still discussed, it has an impact in early disease stages not only to define FIGO staging but also to establish the need for adjuvant treatment, with a significant impact in survival [27, 28]. Blood dissemination is less frequent and usually occurs in advanced disease stages [23, 24].

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A considerable number of clinical-pathological factors have been implicated in OC prognosis. Disease stage, tumor size, histological subtype, differentiation degree, and residual tumor after surgery are considered as the classic prognostic factors. More specifically, the extent of residual disease after surgery is regarded as a major prognostic factor, shown to influence the chemotherapy response and survival [29–33]. Inclusively, a recent meta-analysis has shown that residual tumor is a more powerful prognostic determinant than FIGO stage [31]. The correct histological classification of EOC is also crucial, since it is an independent prognostic factor and provides a guideline for therapeutic management [8, 27]. Performance status (PS) and age are also important factors having an impact on the prognosis and, ultimately, in the

Numerous studies have been conducted to assess the clinical significance of molecular alterations in OC. However, so far, the obtained results do not allow a prognostic biomarker to be universally accepted, although the determination of *BRCA* germline mutations has been recently approved as a predictive biomarker for OC. Recently, the development and the application of new genomic technologies have allowed the description of molecular signatures integrated into prognostic and predictive models. In particular, the Cancer Genome Atlas Project (TCGA) has been critical in adding to our knowledge, as it has been used to confirm the importance of *BRCA* genes to serous OC patients survival, as well as being able to help to describe a transcriptional signature with prognostic relevance [34] (this will be investigated further in a separate chapter).

The therapeutic strategy for EOC is based on cytoreductive surgery and staging, followed by adjuvant chemotherapy with the duplet platinum/taxane [8, 20]. As mentioned above, the extent of surgery is a determinant for survival and response to chemotherapy, since these parameters vary significantly depending on the success (optimal or suboptimal) of the surgical procedure [33]. Systemic therapy with cytotoxic agents plays a fundamental role in the treatment of this neoplasia. Chemotherapy is generally recommended in the EOC, including early stages with histopathological criteria of poor prognosis (FIGOIA/IB G3, FIGO IC, FIGO II, or clear cell histology at any stage). However, stage IA or IB G1 or G2 tumor patients, if adequately staged (i.e., with peritoneal washings, assessment of the contralateral ovary and fallopian tube, pelvic and para-aortic node assessment and omentectomy), have a better prognosis and can be treated with surgery alone without the need for adjuvant chemotherapy [35–37] (**Figure 1**).

**5. Prognostic factors**

decision of medical treatment [27].

**6. Treatment**

**6.1. First-line treatment**
