OVARIAN CANCER TREATMENT IN GERMANY

• Ovarian cancer affects predominantly women in the postmenopausal or perimenopausal stage; the risk is increased by inability to bear children, delayed childbearing, early onset of menstruation, delayed menopause and certain genetic markers.

• Early symptoms (for example, dyspepsia, bloating, early satiety, gas pains, back pain) are non-specific.

• If cancer is suspected, ultrasonography is performed, tumour markers (for example, CA 125) are measured and the tumour is staged surgically.

• Screening asymptomatic women with ultrasonography and/or CA 125 is not informative unless the likelihood of a BRCA mutation is high.

• As a rule, treatment consists of hysterectomy, bilateral salpingo-oophorectomy and chemotherapy (for example, with carboplatin and paclitaxel).

In patients with BRCA1 or BRCA2 gene mutations, the risk of ovarian cancer and, to a lesser extent, of breast cancer is reduced if prophylactic bilateral salpingo-oophorectomy is performed once childbearing is complete. With this approach the cancer risk is lower than with surveillance. Patients with mutations in the BRCA1 or BRCA2 genes should be referred to a gynaecological oncologist for counselling.

Tumour markers

Tumour markers, including the beta subunit of human chorionic gonadotropin (beta-hCG), LDH, alpha-fetoprotein, inhibin and CA 125, are usually measured in younger patients, who are at higher risk of non-epithelial tumours (for example, germ cell or stromal tumours). In perimenopausal and postmenopausal patients only CA 125 is measured, because epithelial tumours predominate in women of this age group with ovarian cancer. In 80% of cases of advanced epithelial ovarian cancer the CA 125 value is elevated, but a slight increase may also occur in endometriosis, pelvic inflammatory disease, pregnancy, fibroids, peritoneal inflammation or non-ovarian peritoneal cancer. A mixed solid or cystic mass in the pelvis in a postmenopausal woman, particularly with an elevated CA 125, is suggestive of ovarian cancer.

Biopsy

Routine biopsy is not recommended except when the patient is a candidate for surgery. In these rare cases, the specimen is obtained by aspiration biopsy (for tumours) or needle aspiration (for ascitic fluid).

If ultrasonography suggests that a mass is benign, histological examination is not required; the ultrasound scan should be repeated after 6 weeks. Such benign masses include benign cystic teratomas (dermoid cysts), follicular cysts and endometriomas.

Asymptomatic women at average risk should undergo a screening gynaecological examination every 1-3 years between the ages of 18 and 40, and annually thereafter. Although data from large clinical studies show that CA 125 has high specificity (up to 99.9% in one study), its sensitivity is moderate (71% in one study) and its positive predictive value is low; CA 125 is therefore not recommended as a screening test for asymptomatic women at average risk. Women without symptoms are screened using ultrasonography and serological measurement of the tumour marker CA 125, which in some cases helps to detect ovarian cancer but does not improve treatment outcomes, even in high-risk subgroups (including women with BRCA gene mutations). Nevertheless, screening for BRCA gene abnormalities is recommended if the family history includes:

• ovarian cancer diagnosed in a first-degree relative before the age of 40;

• breast cancer and ovarian cancer diagnosed in a single first-degree relative, with one of the cancers diagnosed before the age of 50;

• two cases of ovarian cancer in first- and second-degree relatives on the same side of the family;

• two cases of ovarian cancer and one case of breast cancer in first- and second-degree relatives on the same side of the family;

• one case of breast cancer and one case of ovarian cancer in first- or second-degree relatives on the same side of the family, where the breast cancer was diagnosed before the age of 40 and the ovarian cancer before the age of 50;

• two cases of breast cancer in first- and second-degree relatives on the same side of the family, diagnosed before the age of 50;

• two cases of breast cancer in first- and second-degree relatives on the same side of the family, one of them diagnosed before the age of 40.

If a woman of Ashkenazi Jewish descent has a family history of one case of ovarian cancer diagnosed before the age of 50, consideration should be given to screening for abnormalities in the gene BRCA.

When cancer is suspected and once the diagnosis is confirmed, staging is carried out surgically.
If early-stage cancer is suspected, staging may be performed by laparoscopy or robot-assisted laparoscopic surgery. Otherwise, a midline laparotomy is required to access the upper abdomen. All peritoneal surfaces, the right and left hemidiaphragm and all abdominal and pelvic organs are inspected and palpated. Fluid is sampled from the pelvis, the paracolic gutters and the diaphragm, and multiple peritoneal biopsies are taken from the central and lateral parts of the pelvis and the abdominal cavity. In early-stage cancer the omentum is removed and biopsies are taken from the pelvic and para-aortic lymph nodes.

Cancers are also graded histologically from 1 (least aggressive) to 3 (most aggressive). The most recent classifications distinguish epithelial ovarian cancer as low-grade (grade 1) or high-grade (grade 2 or 3).

Five-year survival with treatment:

• Stage I: 70 - 100%

• Stage II: 50 - 70%

• Stage III: 20 - 50%

• Stage IV: 10 - 20%

The prognosis is less favourable with a higher tumour grade and in cases where it is not possible to remove all visibly affected tissue surgically; the prognosis is most favourable if the affected area can be reduced to < 1 cm in diameter or, ideally, to microscopic residual disease (cytoreductive surgery). At stages III and IV the recurrence rate is approximately 70%.