Ovarian cancer

Ovarian cancer is a malignant neoplasm that includes all malignant epithelial tumors of the ovary. These include primarily the serous / serous-papillary, endometrioid and mucinous tumors. Ovarian cancer usually occurs in old age. Symptoms often appear late and include abdominal discomfort in particular.

definition

The ovary is made up of different tissues: epithelium, germ cells, stroma and germ line tissue. Various benign and malignant tumors can develop from these. The term ovarian cancer encompasses all malignant epithelial tumors of the ovary. These include primarily the serous / serous-papillary, endometrioid and mucinous tumors. The serous / serous-papillary tumors are the most common. They are often located bilaterally.

Epidemiology

Ovarian cancer is the 6 most common tumor in women. Epithelial ovarian cancer usually occurs between the ages of 60 and 70. With genetic predisposition, it can also occur at a younger age (<30 years). These patients usually show a familial cluster.

The lifetime prevalence that a malignant tumor of the ovary occurs is 1-2%. Every year around 5500 women in Germany die of ovarian cancer.

causes of ovarian cancer

Certain factors lead to an increased risk of developing ovarian cancer. These include, for example, age, obesity or exposure to asbestos. Also a high number of ovulations, infertility, few pregnancies or endometriosisfavor the occurrence of ovarian cancer. There may also be hereditary risk factors. The best known and most common risk factor is the mutation of the BRCA1 / BRCA2 gene. It is estimated that around 5-10% of all ovarian cancers are caused by this mutation. If this is the case, the lifetime risk of developing ovarian cancer is around 20-40%. Further syndromes that are associated with an increased risk of ovarian cancer are, for example, the HNPCC syndrome (hereditary non-polyposis colorectal carcinoma syndrome) and the Peutz-Jeghers syndrome.

Protective factors include, for example, multiparity, a long period of breastfeeding, the use of ovulation inhibitors and tube ligation.

ovarian cancer pathogenesis

The various histological subtypes of ovarian cancer show different pathogenesis.

Serous low-grade carcinomas often show mutations of b-raf (rapidly accelerated fibrosarcoma) or k-ras (Kirsten rat sarcoma viral oncogene). Precursor lesions of these carcinomas are serous cystadenomas or borderline tumors (adenoma-carcinoma sequence). In contrast, the prognostically less favorable high-grade serous ovarian carcinomas are mostly based on mutations of the p53 tumor suppressor gene (in 95% of cases). They are the most common cancers of the ovary. They often show an association with the BRCA1 / 2 mutations.
Mucinous ovarian carcinomas often show an activating k-ras mutation or an amplification of the Her-2 / neu gene.

Endometrioid carcinomas usually have somatic mutations of ß-catenin and the tumor suppressor gene PTEN. Activation of the PIK-3CA signaling pathway can rarely be pathogenetically significant.

Clear cell ovarian carcinomas show molecular genetic inactivation of the tumor suppressor gene ARIDIA-1A, a deletion in the PTEN gene or an activation of the PIK-3CA signaling pathway.

Ovarian Cancer Symptoms

Ovarian cancer usually has no specific symptoms in its early stages. These usually only occur in advanced stages

ovarian cancer symptoms include:
abdominal complaints (e.g. nausea, bloating, changes in bowel habits, ascites, abdominal pain) but also dyspnoea in the presence of a pleural effusion and tumor cachexia. Menstrual cycle disorders and postmenopausal bleeding are also possible.

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Diagnosis

The diagnosis begins with the patient's medical history.

Early detection screening

Screening for the early detection of ovarian cancer is currently only recommended by the guideline for populations at risk. Genetic testing is to be offered to them. Due to the low effectiveness of the screening methods currently available (transvaginal ultrasound and Ca125) in terms of improving the prognosis, these high-risk patients should be informed about the possibility of a prophylactic operation (bilateral salpingo-oophorectomy).

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Primary diagnostics

The guideline recommends the initiation of diagnostic measures in patients over the age of 50 if the following symptoms persist: bloating, flatulence, unexplained abdominal pain or discomfort and an increase in the frequency of urination. A gynecological examination including a mirror and palpation examination and a transvaginal sonography should then be carried out. Transvaginal sonography is initially the imaging method of choice. Computed tomography or magnetic resonance tomography can be used for special questions. This is particularly the case for the differential diagnosis of a gastrointestinal primary tumor.

Staging

Ovarian carcinomas are classified according to the TNM and FIGO classification.
The histological grading of this tumor entity is carried out according to the WHO classification, but also according to the FIGO grading system, GOG grading system and the Silverberg grading system.
The TNM / FIGO classification is based on the local tumor spread (T), the lymph node involvement and the presence of a distant metastasis.

Table 1: TNM / FIGO classification of ovarian cancer

For further information, please refer to the AWMF guidelines.

therapy

Operational measures

Operative staging in early ovarian cancer

The guideline recommends adhering to the following surgical steps for optimal surgical staging of early ovarian cancer (FIGO stages I to IIA):

After performing a longitudinal laparotomy, an inspection and palpation of the entire abdominal cavity and a peritoneal cytology are performed. The next steps are the removal of biopsies from all suspicious areas and the removal of peritoneal biopsies from inconspicuous regions. This should be followed by an extirpation of the adnexa on both sides and a hysterectomy with an extraperitoneal procedure if necessary. In addition, an omentectomy should be performed at least infracolically, an appendectomy (for mucinous and unclear tumor type) and a bilateral pelvic and para-aortic lymphadenectomy.

Staging in early ovarian cancer is particularly important so that any further tumor manifestations that may be present can be discovered in order to be able to carry out any necessary changes to the subsequent systemic therapy. Up to 30% of patients with supposedly early ovarian cancer have occult lymph node metastases and are therefore classified as FIGO III. Compared to patients with incomplete staging, complete staging resulted in better progression-free survival and overall survival.

Surgical therapy for advanced ovarian cancer

Ovarian cancer should be completely resected as part of the primary surgery. The best results are usually achieved by gynecological oncologists who specialize in these operations. Epithelial ovarian carcinoma spreads intraperitoneally throughout the abdomen from the pelvis to the diaphragm. For this reason, a multivisceral resection may be required in advanced ovarian cancer if it enables a complete resection, an obstruction (e.g. of the intestine) to be removed and there are no contraindications for the extensive operation.

The guideline also recommends that patients with advanced ovarian cancer undergo debulking surgery and then undergo chemotherapy. It is recommended to refrain from neoadjuvant chemotherapy due to the worsening prognosis.

Systemic primary therapy

The guideline recommends performing adjuvant carboplatinous chemotherapy over six cycles from stage IC or IA / IB and grade 3. From stage IAG2, IBG1 / 2, patients can be offered chemotherapy.

Patients with advanced ovarian cancer (IIb-IV) should be offered first-line chemotherapy consisting of carboplatin AUC 5 and paclitaxel 175 mg / m2 over six cycles every 3 weeks. It is also possible to have an additional treatment with bevacizumab.

Tumor follow-up

Follow-up care for ovarian cancer serves on the one hand to identify a possible relapse, but also to identify and treat therapy-associated side effects, rehabilitative measures, psychosocial care and reintegration of the patients. It also aims to improve the quality of life. The guideline recommends that follow-up care should include a detailed medical history, a physical exam including a gynecological mirror and palpation exam, a rectal exam, and a vaginal sonography.

For further information, please refer to the AWMF guidelines.

forecast

Since ovarian carcinomas do not attract attention with symptoms until late, approx. 75% of ovarian carcinomas are only diagnosed at an advanced stage. The relative 5-year survival rate (5JÜR) is around 40% across all stages. In stage I the 5JÜR is highest at approx. 85-95% and then decreases rapidly in stage IV. Here the 5JÜR is only approx. 15-20%. The tumor stage at initial diagnosis is therefore one of the most important prognostic factors for ovarian cancer.

It has been shown that the prognosis improves if a complete intra-abdominal resection is performed in ovarian cancer. In general, it can be said that the quality of therapy with adherence to the therapy standards determines the prognosis. Another independent prognostic factor in studies was the age and general condition of the patients. The histological subtype of the tumor also has an influence on the prognosis for ovarian cancer. A better prognosis for serous-papillary and endometrioid carcinomas compared to clear-cell and mucinous tumors could be shown. The clear-cell and mucinous tumors also respond less well to platinum-based chemotherapy.
Another prognostic factor is the histological grading. Good differentiation is associated with a better prognosis and vice versa.

prophylaxis

The most effective measure to reduce the risk of disease and mortality in hereditary ovarian cancer is bilateral salpingo-oophorectomy. This can reduce the risk of illness by 80 to> 90%. The risk of breast cancer in these patients can also be reduced by the operation, albeit to a lesser extent. The guideline recommends offering this operation to high-risk patients with a proven BRCA1 / 2 mutation after family planning has been completed, but only after the age of 40 or 5 years before the youngest woman in the family developed ovarian cancer.

Hints

If ovarian cancer occurs at a young age or if the disease occurs in families, a genetic predisposition must be considered, in particular the BRCA1 / 2 mutation. This not only increases the risk of developing ovarian cancer , but also the risk of developing breast cancer .