**5. Prognostic factors**

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

Ovarian cancer staging is surgical, being performed according to the International Federation of Gynecology and Obstetrics (FIGO) criteria [22]. CT or magnetic resonance imaging scans, although of limited impact for OC early diagnosis, allow to establish a surgery plan and to determine tumor irresectability criteria for 70–90% of all patients. The ability to detect peritoneal implants in both exams depends upon their location, size, and the presence of ascites. However, CT is the imaging modality of choice for OC staging, since it is indispensable for the preoperative evaluation to optimize maximal cytoreduction surgery or to help in the decision

Ovarian cancer dissemination can occur through all known propagation routes, i.e., lymphatic, hematogenic, transcavitary, and contiguous. The transcavitary course is undoubtedly the most clinically relevant and, in the vast majority of cases, has an impact on the patient prognosis [23, 24]. The dissemination to the peritoneal cavity is an early phenomenon in the natural history of the disease, since the malignant cells follow the peritoneal fluid, flow concerning intra-abdominal pressure variations. Ovarian cells are characterized as anchoragedependent cells, meaning that they could only survive when adherent to the extracellular matrix or in contact with neighbor cells. However, when OC cells exfoliate into the peritoneal cavity, they can avoid anoikis (apoptosis process triggered by the loss of binding to the extracellular matrix) and survive even when isolated. Cancer cells in this state can survive and disseminate into the peritoneum, depositing accordingly to the passive flow distribution of peritoneal fluid, predominantly into the paracolic gutters, diaphragmatic surfaces, liver capsule, intestine surface, and omentum. The adhesion of malignant cells to the peritoneum precedes the local invasion and the secondary metastasis, namely to the pleural cavity by the transdiaphragmatic pores (Stage IV) [25]. The transcavitary route seems to be related to the OC cells predilection for the abdominal cavity (homing) rather than the deposition in other organs such as liver, lungs, brain, or bone (rarely in these latter two locations). The dissemination by contiguity is also important and of particular interest for organs like fallopian tubes, uterus, contralateral appendix and bladder, rectum, and pouch of Douglas. The iatrogenic route by contiguity, for example, to the abdominal wall is less frequent. Lymphatic dissemination is frequently observed when the disease is confined to the ovary, being found in almost 15% of FIGO I–II cases [26]. In fact, for a proper FIGO staging, lymphadenectomy is required, and the removal of bulky lymph nodes should be performed to achieve complete macroscopic resection. Although the systematic lymphadenectomy in advanced OC surgical management

malignant, are rare, representing 3–5% of all OC cases [2, 21].

**4. Staging**

of neoadjuvant chemotherapy.

60 Ovarian Cancer - From Pathogenesis to Treatment

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 decision of medical treatment [27].

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).
