Ovarian cancer
What is it?
Epithelial carcinoma of the ovary (ovarian cancer) is a neoplasm arising from the epithelial cells of the female gonad and accounts for about 90% of all ovarian cancers. It accounts for 30% of cancers of the female genital tract and is the fourth leading cause of death from malignant neoplasia in women in industrialized countries.
The incidence of this disease in industrialized countries is increasing, at around 17 cases per 100,000 per year, with a mortality rate of 12/100,000 per year; in 60-70% of cases it exits at an advanced stage. Ovarian cancer affects approximately 1.5 people per 10,000 in Italy. In 2020, according to ISTAT data, there were more than 5,000 deaths from ovarian cancer in Italy.
Epithelial tumors of the ovary represent a heterogeneous group of neoplasms. Histologically, five main subtypes are recognized:
- high-grade serous carcinoma (70%), usually presenting in an advanced stage and with involvement of both ovaries;
- low-grade (< 5%) serous carcinoma, distinguished from the former by "low-grade" nuclear features and low mitotic index;
- mucinous carcinoma (3%), consisting of neoplastic cells resembling gastric, intestinal, or endocervical epithelium. The large size and unilaterality of the neoplasm are the main parameters to differentiate it from a metastasis;
- endometrioid carcinoma (10%), a low-grade adenocarcinoma associated with foci of ovarian or pelvic endometriosis;
- clear cell carcinoma (10%), usually occurring at an early stage and associated with endometriosis.
Further classification takes into account the pathogenetic mechanism and molecular alterations that support the genesis of these tumors. Two groups can be recognized:
- type I, with mutations on KRAS, BRAF, PTEN, PIK3CA, CTNNB1, and ARID1A, includes endometrioid, clear cell, mucinous, and low-grade serous carcinomas, emerging mainly from foci of atypical endometriosis;
- type II, with mutations on P53, mainly including high-grade serous carcinomas, which originate from the tubal epithelium and may be associated with mutation of BRCA genes.
Causes and risk factors
Risk factors for epithelial ovarian carcinoma include:
- advanced age: the risk of ovarian cancer increases with age. In fact, about half of ovarian cancers occur in women over the age of 60;
- family history of ovarian cancer;
- genetic factors: about 10% to 15% of ovarian cancers are due to genes that increase the likelihood of developing cancer (most commonly BRCA1/2 mutations);
- nulliparity (condition of the woman who has never given birth): multiparity and breastfeeding are considered protective factors for ovarian cancer;
- endometriosis: a condition characterized by the presence of ectopic endometrial tissue, that is, outside its normal site (uterus);
- overweight and obesity;
- early menarche and/or late menopause because the high number of ovulations subjects the ovary to greater cell turnover and thus to the risk of more DNA errors.
Which are the symptoms?
Ovarian cancer is a very insidious disease because it has nonspecific signs and symptoms such that early diagnosis is difficult. Symptomatology is generally represented by:
- asthenia;
- generalized abdominal pain, abdominal distension, gradual and continuous increase in abdominal girth, bloating and/or feeling full even after a light meal;
- nausea, diarrhea or constipation;
- unexplained weight loss or gain;
- inappetence;
- abnormal vaginal bleeding or menstrual changes;
- dyspareunia;
- dysuria or increased frequency of urination;
- lumbago.
Therefore, this symptomatology is often ascribed to less serious conditions such as weight gain, indigestion, or aging and thus very often underestimated.
How is it diagnosed?
The diagnostic process for ovarian cancer begins with the collection of a thorough personal and family history and subsequent gynecologic examination of the patient, which consists of vaginal and rectal exploration of the pelvis combined with abdominal palpation.
Transvaginal and abdominal ultrasound is the most widely used diagnostic test for diagnosis and/or confirmation of clinical suspicion of pelvic masses. In addition, it is important to assay serum markers such as CA125 and HE4. CEA and CA19.9 assay may be useful in differential diagnosis with gastrointestinal diseases.
If clinical suspicion is confirmed, the patient should undergo additional examinations aimed at tumor staging, that is, to check the spread of the tumor and the presence of any metastases:
- Chest X-ray or chest CT;
- CT abdomen-pelvis with and without contrast medium;
- MRI pelvis with and without contrast medium;
- total body PET scan.
Definitive diagnosis of ovarian carcinoma is made by histological examination after surgery.
Suggested exams
How is it treated?
Surgery represents the first line of treatment. Cytoreductive surgery (removal of macroscopically visible tumor) involves not only removal of uterus and adnexa, but also omentum (peritoneal formation) and other tissues/organs if affected by disease. Depending on the stage of the tumor, treatment after surgery includes chemotherapy with carboplatin and paclitaxel.
If primary cytoreductive surgery is not possible, a diagnostic laparoscopy is performed followed by neoadjuvant chemotherapy according to a standard schedule, followed by interval surgery and completion with an additional 3 cycles of chemotherapy.
In first-line treatment of cancer and relapse, there are also maintenance target drugs such as the monoclonal antibody Bevacizumab, which counteracts tumor neoangiogenesis, and inhibitors of PARP (olaparib, niraparib, and rucaparib), i.e., the protein involved in DNA repair processes. These are chosen on the basis of molecular diagnostic assessments and response to platinum-based chemotherapy treatment.
Radiation therapy is applied for palliative purposes for some metastatic sites.
Clinical trials for the treatment of ovarian cancer are also available in our center.
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Where do we treat it?
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