Rationale
Ovarian cancer is the most common cause of death for the gynaecological malignancies. It is highly curable in the early stages (> 90%) but fatal in advanced stages despite modern therapy. It commonly produces a detectable serum tumour marker (CA125) and is also detectable with ultrasound, an imaging test that does not use ionising radiation.
Arguments against screening include that the progression of disease from the ovary to regional and distant disease is not well understood. The diagnostic tests after a positive screening tests are very invasive (at least laparoscopy). CT scanning is completely ineffective as a screening test.
Modern tests have not proven successful for population based screening in trials due to poor sensitivity and specificity of CA125 in early stages of the disease.
Screening remains an important component of care for patients at elevated risk of ovarian cancer due to familial history or germline mutations. The lifelong risk of ovarian cancer is:
- BRCA1: 40-50%
- BRCA2: 20-25%
- Lynch Syndrome: 10%
- Average person: 2%
Evidence
CA125
Multiple randomised studies have established that the positive predictive value of CA125 is about 3% - that is, for every women with a positive CA125, 33 would undergo an unnecessary laparoscopy. This is not thought to be beneficial.
Ultrasound
Ultrasound has been evaluated in several population cohorts. When used a screening test, it rarely picks up early stage disease.
Screening Questionnaire
Given the vague symptoms associated with ovarian cancer, it has been proposed that patients undergo a screening questionnaire to determine their risk of disease. Alone, this test has low sensitivity and specificity and its role in screening is questionable.
Combination
Combining the above tests may improve the overall sensitivity and specificity. This was evaluated in the PLCO trial which randomised patients to annual CA125 and transvaginal ultrasound versus usual care. This demonstrated both an increased number of diagnoses of ovarian cancer and no impact on ovarian cancer mortality, suggesting overdiagnosis. Additionally, a large number of women underwent surgical procedures for false-positive results, and about 1/6 had complications from their surgery.
Summary
Ovarian cancer screening in the general population has proven futile with currently available tests. The main problem is the low sensitivity and positive predictive value, particularly for the early stage tumours.
Targeted Screening Programs
Screening in high risk women should potentially reduce the numbers of false positive tests due to the higher incidence. However, studies of screening in these populations have also been disappointing, with numerous cancers arising despite screening. There have been no randomised studies evaluating screening in these populations. Therefore, patients should:
- Have oophrectomy (or hysterectomy/oophrectomy) at completion of childbearing
- Undergo screening from the age of 25 in an attempt to detect malignancy early
