Ovarian cancer is not a single disease, but represents a heterogeneous group of diseases both clinically, pathologically, and molecularly. It is the second deadliest cancer in women worldwide, after cervical cancer.

Are there risk factors I can avoid to reduce my chance of getting sick?

“Infertility, estrogen therapy and obesity are risk factors, and these are responsible with the data so far for the increase in the incidence of ovarian cancer in developed countries. On the contrary, the use of contraceptives especially for long periods and breastfeeding seem to protect the female organism from the disease.

Childbearing, early menopause, and tubal ligation are associated with a decreased risk of endometrioid carcinoma as well as ovarian clear cell carcinoma, while endometriosis is associated with an increased risk of these types. Serous and poorly differentiated ovarian cancers are moderately associated with childbearing and hormone therapy in postmenopausal women, and are more strongly associated with a hereditary history of ovarian cancer.

More specifically, patients who carry gametic mutations of the BRCA1/2 genes have a 16-65% increased risk of ovarian cancer mainly of high-grade serous type. Women with mutations in DNA repair genes (mismatch repair genes-Lynch syndrome) have a 10%-12% lifetime risk of developing ovarian cancer,” explains Ms. Eleni Aravantinou – Fatorou MD, MSc Pathologist OncologistMetropolitan Hospital.

Can I have a preventive test for ovarian cancer? What are the symptoms?

“Unfortunately, there is no preventive method for ovarian cancer to date. Cancer antigen 125 (CA-125) measurement is not recommended in the healthy population. An elevated CA-125 value is not diagnostic of ovarian cancer, as it can be elevated in other conditions, both malignant and benign (for example, endometriosis and ovarian cysts). CA-125 is elevated in about half of women with stage I ovarian cancer. In contrast, it is elevated in about 85% of women with advanced ovarian cancer.

Most women are diagnosed after the presence of symptoms, which usually occur in advanced stages. The most common symptoms include abdominal pain, constipation, diarrhea, frequent urination, vaginal bleeding, abdominal distention, and fatigue. At a more advanced stage, ascites and abdominal masses lead to nausea, anorexia, indigestion and early satiety,” says the expert.

Pathoanatomical Classification: Ovarian cancer is not one disease, but many.

In 2020 the World Health Organization based on histopathology, immunohistochemistry and molecular analysis recognized five distinct subtypes of malignant epithelial ovarian cancer: highly malignant serous ovarian carcinoma which constitutes 70% of cases, endometrioid carcinoma (10%), clear cell carcinoma (6%-10%), low malignant serous carcinoma (5%) and mucinous carcinoma (3%-4%) as well as some rarer types. “Each subtype is a separate disease with a different onset, pathogenesis, clinical features and prognosis. This complex sub-categorization has an impact on the individualized treatment that will follow and shows the necessity of the diagnosis by an experienced pathologist”, he emphasizes.

How is early disease treated?

“Surgical resection is the treatment of choice in early ovarian cancer. The aim of the surgery is to rule out the disease and correct staging by removing pelvic and paraaortic lymph nodes in highly malignant histology. The probability of lymph node involvement in low-grade ovarian endometrioid carcinoma is <1%, and therefore lymphadenectomy in these cases can be avoided. In young low-stage and high-risk women, a more limited fertility-preserving surgery could be discussed. Complementary chemotherapy based on platinum is given according to stage and histological type and improves the overall survival and the time until the relapse of the patients" points out Mrs. Aravantinou-Fatorou.

How is advanced ovarian cancer treated?

“In advanced disease the goal of surgery is to achieve complete or optimal cytoreduction. The timing of surgical cytoreduction versus chemotherapy is still debated. Decisions must be made by oncology boards at specialized centers. The best common practice in patients with stage III-IV disease is primary cytoreductive surgery if the patient is physically fit for surgery and complete resection appears feasible, followed by systemic therapy. Primary cytoreductive surgery is also recommended in patients with less chemosensitive subtypes (such as poorly differentiated serous or mucinous carcinoma).

Systemic chemotherapy is indicated for all patients with advanced ovarian cancer. The chemotherapy of choice includes 6 cycles of paclitaxel and carboplatin. The addition of bevacizumab, an antiangiogenic monoclonal antibody, to chemotherapy and later as maintenance therapy showed a benefit in time to relapse, while a benefit in overall survival was shown only for high-risk patients. The introduction of PARP inhibitors (olaparib, niraparib, rucaparib, which play a role in DNA repair) as maintenance therapy greatly improved time to relapse, patients’ quality of life and overall survival,” he explains and continues:

“All patients with advanced ovarian cancer should undergo two tests: screening for mutations in the BRCA 1/2 genes and screening for HRD status, which are prognostic indicators for the disease and predictive of the treatments administered. Over 50% of high-grade serous ovarian cancers are HRD positive, including 15%–20% of cases with gametic (ie, inherited) mutations of the BRCA 1/2 genes. Somatic BRCA 1/2 mutations are usually due to epigenetic changes and are frequently involved in the remaining percentage of HRD positive ovarian cancers. Why do we care about this information about our patients? Because based on these data we will decide the optimal maintenance therapy, which includes PARP inhibitors as monotherapy, bevacizumab as monotherapy and the combination of bevacizumab with PARP inhibitors.

Regarding patients with low-grade serous ovarian cancer who express a high concentration of estrogen and progesterone receptors, it appears from retrospective studies that hormonal therapy has a place as a maintenance treatment.

“Significant progress has been made in recent years in ovarian cancer with the addition of the above innovative treatments. However, despite high response rates to first-line therapy 70% of patients will relapse within the first three years. We need to try more to improve the chance of a cure. Some early results from the combination of chemotherapy, anti-angiogenic agent, PARP inhibitors and immunotherapy are promising in this difficult disease. We await the results of the combination, but also the entry of new drugs, conjugated molecules with new, smarter modes of action that we hope will stop the course of advanced ovarian cancer,” concludes Ms. Aravantinou – Fatorou.