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Ovarian Cancer

Table of Contents
1 Disease Overview
        1.1 Diagnosis
        1.2 Types
        1.3 Risk Factors and Prevention
        1.4 Screening
        1.5 History, Symptoms and Signs
        1.6 Diagnosis and Tumour Assessment
2 Staging
3 Stage Grouping
4 Treatment Modalities
        4.1 Surgery
        4.2 Radiation Therapy
        4.3 Chemotherapy Therapy
5 Follow-up
6 Pivotal Trials

Disease Overview

    In 2014, Statistics Canada estimated 2,700 new cases and 1,750 deaths, making ovarian cancer the leading cause of gynaecologic cancer death. Ovarian cancers account for 4% of cancers among females. Approximately 1 woman in 70 will develop ovarian cancer, with a mean age of 59.

Diagnosis

    For premenopausal women, most ovarian masses are functional cysts that typically decrease in size after several menstrual cycles. Conversely, in postmenopausal women, a palpable pelvic mass indicates the presence of malignant disease. Subsequent CT scans of the chest, abdomen, and pelvis can determine the spread of the tumour, but cannot confirm whether the disease is from an ovarian cancer primary. Definitive diagnosis of ovarian cancer is made by surgical exploration, with prognosis associated with the amount of residual tumours following surgical cytoreduction. For patients where optimal cytoreduction or surgery is not an option, a biopsy may be done to confirm a diagnosis.

    Ovarian cancer is a common cause of gynecologic tumour mortality.

Types

  • Epithelial ovarian cancer (EOC): This type of ovarian cancer comprises of 70% of all ovarian tumours. It is the sixth most common cancer in women. Symptoms are often vague or non-specific, often delaying diagnosis until disease is advanced.
  • Tumours of low malignant potential (LMP): These borderline tumours are an EOC subtype, and they comprise approximately 20% of all ovarian tumours. LMP tumours are less aggressive than typical EOCs, tend not to be invasive, and are mostly stage I at presentation.
  • Malignant germ cell tumours (GCT): This category includes dysgerminoma (the most common type), endodermal sinus tumour, malignant teratoma, embryonal carcinoma and choriocarcinoma. Ovarian GCTs are rare tumours that tend to grow rapidly and spread throughout the lymphatics.
  • Sex-cord stromal tumours: This category makes up less than 5% of all ovarian neoplasms and includes tumours of the sex cords, granulosa cells, Sertoli cells, Leydig cells, and combined Sertoli-Leydig cells. Their behaviour is less malignant than EOC.
  • Rare tumours: Rare ovarian tumours include small-cell carcinoma, mixed mesodermal sarcoma (carcinosarcoma) and metastatic tumours arising from a variety of sites.

Risk Factors and Prevention

    Epithelial ovarian cancer (EOC): Increasing age is one of the most influential risk factor for developing ovarian cancer, followed by family history.

    A woman with a first degree relative with ovarian cancer has a 5% lifetime risk for ovarian cancer. Caucasian race, a diet high in animal fat, and mutations in the BRCA-1, BRCA-2, and HNPCC genes is also a significant risk factor. Nulliparity or first birth after 35 , early menarche, and late menopause increases the risk of ovarian cancer as each factor is associated with uninterrupted periods of ovulation which increases the probability of genetic errors occurring during repair of ovary surface epithelium. Additionally, women ingesting oral contraceptives have a reduced risk of ovarian cancer by 50% over a 5 period use compared to women who are never-users.

    Risk is reduced with childbearing, combined oral contraceptive use for at least five years, tubal ligation, and bilateral oophorectomy.

Screening

  • Epithelial ovarian cancer (EOC): No screening program exists for ovarian cancer, although high-risk individuals should consider annual ultrasound and cancer antigen 125 (CA 125) level testing, prophylactic oophorectomy, or clinical trial participation, if available.
  • Malignant germ cell tumours (GCT): Many GCTs frequently produce markers that are useful at diagnosis, for monitoring response, and for follow-up.
    • Endodermal sinus tumours: α-fetoprotein
    • Choriocarcinoma and dysgerminomas: β-hCG
    • Dysgerminoma: lactate dehydrogenase and placental alkaline phosphatase.

History, Symptoms and Signs

    Epithelial Ovarian Cancer presents with a broad range of vague and non-specific, but primarily, abdominal or pelvic symptoms which may include bloating, discomfort, constipation, indigestion, vaginal bleeding, shortness of breath, and fatigue. The patient may feel an abdominal mass. TMP may have a similar presentation, or identification of an asymptomatic tumour may be an incidental finding. Patients with malignant GCTs may present with abdominal pain or distension, vaginal bleeding or fever.

Diagnosis and Tumour Assessment

    Ultrasound is the most helpful initial investigation in a patient with a pelvic mass. Routine investigations include hematology, chemistry panel, and CA125 testing. Chest X-rays are recommended, and CT scans can detect metastases and provide an indication of tumour operability. Ovarian histopathology provides a definitive diagnosis. Tumour markers may be elevated in GCT.


Staging

    Surgery for staging and tumour cytoreduction plays a key role in the management of epithelial ovarian cancer. It determines prognosis and management. Important prognostic factors include stage of disease, optimal vs suboptimal cytoreduction, tumour grade (particularly for stage I cancers), poor risk histology such as clear cell and mucinous cancers, patient age, and performance status.


Stage Grouping


Treatment Modalities

    Similar to testicular cancer, germ cell tumour of the ovary is curative with systemic therapy using platinum-based regimens.

Surgery

    Surgery has usually been the first step in staging and treating epithelial ovarian cancer. Surgery is the definitive treatment for Stage IA or IB, grade I or II ovarian cancer with excellent survival (90%) and no further adjuvant therapy is required. However for high risk, early stage ovarian cancer, adjuvant chemotherapy with platinum-based agents and taxanes prolongs survival, and is recommended after surgical resection.

Radiation Therapy

    The role of radiation in early stage ovarian cancer is not indicated or recommended. Advanced cancers are often treated by chemotherapy, radiotherapy, or both, after the initial debulking surgery.

Chemotherapy Therapy

    Platinum and taxane-based chemotherapy is standard treatment for advanced ovarian cancer; either before or after surgery. Given before surgery, chemotherapy reduces the size of the tumor, making it easier to remove. After surgery, chemotherapy is used to destroy any remaining cancer cells.

For chemotherapy regimens, refer to: http://www.cancercareontario.com/


Follow-up

    Specific follow-up recommendations are based on the tumour type, stage at diagnosis, surgical outcome, and response to chemotherapy, if used. Regular follow-up is, however, necessary, and generally includes clinical examination, hematology and chemistry panels, imaging, and evaluation of tumour markers (if elevated initially).

  • Tumours of low malignant potential (LMP): Clinical examination and CA 125 levels; annual ultrasound may be appropriate if either or both ovaries are present.
  • Sex-cord stromal tumours: Granulosa cell tumours may secrete inhibin, which can be used as a tumour marker.

    Detailed follow-up schedules for disease-free patients depend on histopathologic diagnosis and disease stage. Goals of follow-up include: early recognition and treatment of potentially curable recurrences or a second primary; identification of symptoms related to metastatic disease, followed by appropriate work up and prompt treatments; and identification and management of treatment related complications, i.e. increased risk of cardiovascular disease in long term survivors related to chemotherapy, radiation and tobacco use, early menopause, pulmonary toxicity, anxiety etc., or increased risk of other cancers due to chemotherapy.

    Survivors with germ cell tumours of the ovary as in testicular cancers need specialized follow-up and close attention to monitoring and prevention of late effects of cancer therapy. Physicians should also encourage healthy lifestyles and provide survivors with provision of ongoing psychosocial support. Generally, history and physical examination and assays of markers alpha FP, beta HCG (for germ cell tumours) and LDH, CA125 are performed frequently and supplemented with periodic abdominal and CT scans and other tests as indicated.


Pivotal Trials

William P. et al. Cyclophosphamide and Cisplatin Compared with Paclitaxel and Cisplatin in Patients with Stage III and Stage IV Ovarian Cancer. N. Engl J Med., 1996