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Ovarian cancer (diagnosis (Symptoms are most commonly seen with advanced…
Ovarian cancer
diagnosis
- Symptoms are most commonly seen with advanced disease
- Symptoms of all stages include abdominal or pelvic pain, constipation, diarrhoea, urinary frequency, vaginal bleeding, abdominal distension and fatigue.
- In advanced ovarian cancer, ascites and abdominal masses lead to increased abdominal girth, bloating, nausea, anorexia, dyspepsia. Extension of disease across the diaphragm to the pleural cavities can produce pleural effusions and the development of respiratory symptoms. Patients may become aware of an abdominal or nodal mass either in the inguinal region, axillae or the supraclavicular fossa
- Following a full clinical assessment, measurement of serum CA 125 is routinely used to aid diagnosis. However, its utility to detect early disease is questionable as it is elevated only in about 50% of patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I disease.
- In advanced disease, CA 125 is elevated in about 85% of patients.
- It is not specific for ovarian cancer and raised CA 125 levels may be found in nongynaecological malignancies (e.g. breast, lung, colon and pancreatic cancer) and benign disease (e.g endometriosis, pelvic inflammatory disease and ovarian cysts).
- Ultrasonography of the abdomen and pelvis is usually the first imaging investigation recommended for women in whom ovarian cancer is suspected
- Transvaginal ultrasonography has improved the visualisation of ovarian structures, thus improving the differentiation of malignant versus benign conditions
- Computed tomography (CT) scans are routinely used to determine the extent of disease and to aid in surgical planning.
- Imaging of the chest with CT or chest X-ray should be done to look for pleural effusions and disease above the diaphragm. A pleural effusion cannot be regarded as malignant and indicative of FIGO stage IV disease without confirmation of positive cytology.
- Magnetic resonance imaging (MRI) scans do not form part of routine investigations.
treatment
- The aim of surgery for early ovarian cancer is to resect the tumour and to undertake adequate staging.
- Adequate, non-fertility-sparing surgery should consist of peritoneal washings, ideally taken before manipulation of the tumour, bilateral salpingo-oophorectomy, hysterectomy, multiple peritoneal biopsies of all abdominal fields, at least infracolic omentectomy, appendectomy in case of mucinous histology and pelvic and para-aortic lymph node dissection up to the renal veins.
- Patients with stage IA or stage IC with unilateral ovarian involvement and favourable histology, that is mucinous, serous, endometrioid or mixed histology and grade 1 or 2, would be amenable to organ-preserving surgery, but only in combination with complete surgical staging.
- This would include a lymphadenectomy to exclude more advanced disease.
- In large retrospective analyses, women with G3 disease or stage IC with clear-cell histology had a higher risk of recurrence.
chemotherapy
- Standard chemotherapy consists of a combination of paclitaxel 175 mg/m2 and carboplatin AUC 6-5, both administered intravenously every 3 weeks
- Usually six cycles of treatment are given
- For those patients who develop an allergy to or do not tolerate paclitaxel, the combination of docetaxel-carboplatin or pegylated liposomal doxorubicin (PLD)-carboplatin can be considered an alternative, based on two randomised clinical trials that showed similar efficacy
- Alternative schedules of administration of paclitaxel and platinum chemotherapy have included intraperitoneal delivery and dose-dense regimens.
targeted therapy
- Angiogenesis is an important component driving the growth of ovarian cancer.
- Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor at 15 mg/kg, with carboplatin and paclitaxel and for ≤15 months or until progression.
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Pathology
- Epithelial carcinoma is the most common histologic type and serous is the most common subtype. Primary fallopian tubal cancer and peritoneal serous carcinoma have been considered rare malignancies.
subtypes
- Serous, endometrioid, clear cell, mucinous, Brenner (transitional cell), mixed epithelial tumours, undifferentiated, unclassified
Grade
- GX: Grade cannot be assessed (undetermined grade)
- G1: Well differentiated (low grade)
- G2: Moderately differentiated (intermediate grade
- G3: Poorly differentiated( high grade)
- G4: Undifferentiated (high grade)
Molecular pathogenesis*
- recognised as a heterogeneous disease, and in the last few years a dualistic model for the pathogenesis of this disease has emerged which divides epithelial tumours into type 1 and type 2 ovarian carcinomas.
- Type 1 cancers tend to be low-grade and indolent tumours and include low-grade serous, endometrioid, mucinous, clear-cell and malignant Brenner tumours.
- These tumours are characterised by mutations of KRAS, BRAF, ERBB2, PTEN, PIK3CA and ARID1A and are relatively genetically stable.
- These mutations occur early in the evolution of type 1 ovarian tumours and are also observed in borderline tumours and endometriosis.
- Type 2 tumours are very frequently associated with TP53 mutations. Approximately 20% of these tumours also carried a BRCA1/2 mutation due to a combination of germline and somatic mutations .
Risk factors
- Age, (verage age at diagnosis in the US is 63 years old.),
- Reproductive and hormonal factors: increased in women with infertility and reduced in those who take oral contraceptives or are multiparous.
- Endometriosis: associated with some histologic subtypes of EOC ( increased risk of clear cell, endometrioid, and low-grade serous EOC)
- Intrauterine device, smoking,
- Family history: BRCA 1 and BRCA 2
- Lynch syndrome (hereditary nonpolyposis colon cancer)
- Polycystic ovarian syndrome
- Women with hereditary ovarian cancer tend to develop the disease ∼10 years earlier than women with non-hereditary ovarian cancer.
staging
- FIGO staging remains the most powerful indicator of prognosis ( read about it)
- Ovarian cancer is the second most common gynecologic malignancy in developed countries
- In developing countries, it is the third most common gynecologic malignancy (cervical cancer is the most common)