B25. Tumor markers of malignant ovarian cancer. Diagnosis and treatment of borderline ovarian cancer.

Tumour markers

Tumour markers in ovarian cancer are not used for diagnosis but rather for preoperative evaluation and follow-up. They’re not appropriate for screening of the general population.

Several biomarkers are available for ovarian cancer:

• Typical for epithelial tumours
  • CA 125
  • CEA
  • HE4 (human epididymis protein 4)
• Typical for germ cell tumours
  • β-hCG
  • AFP
• Typical for granulosa cell tumours
  • Inhibin B
  • Anti-Müllerian hormone

Of these, CA 125 is the most widely used. Up to 80% of endothelial ovarian cancers will have elevated CA 125. It’s elevated if > 35 units/mL. It’s specificity for ovarian cancer is high in postmenopausal women but low in premenopausal. It should be routinely measured in postmenopausal women with adnexal masses, and, if elevated, should raise suspicion of malignancy.

CEA can be elevated in many conditions other than ovarian cancer, benign and malignant, including GI tract cancer, smoking, liver disease, gallbladder disease, IBD, etc.

β-hCG and AFP are mostly elevated in germ cell tumours and choriocarcinoma.

Inhibin is only elevated in sex cord-stromal tumours. Oestrogens and androgens could be elevated in these tumours as well.

Biomarker panels

Several biomarker panels, which measures multiple biomarkers, are available. These use multiple biomarkers to assess the likelihood of malignancy in patients with adnexal mass. Combining biomarkers makes them more sensitive and more specific.

• ROMA index is the most important and uses two biomarkers
  • CA 125 and HE4
• OVA1 uses five biomarkers
• Overa uses five different biomarkers

The RMI (Risk of Malignancy Index) can be calculated to predict the risk that an adnexal mass is malignant. This calculation requires ultrasound features and the CA125 level.

Borderline ovarian tumour

Borderline ovarian tumours are epithelial ovarian tumours of low-grade malignant potential. They are characterised by atypical growth but no stromal invasion. They sometimes have intraperitoneal spread. Borderline tumours account for 15% of epithelial tumours. They mostly affect postmenopausal women. Borderline tumours have an excellent prognosis (5-year survival > 90%).

There’s nothing in particular which can distinguish borderline tumours from other tumours clinically. The diagnosis is made pathologically, after surgery.

Management

Most patients with epithelial ovarian carcinoma are treated by surgical removal or cytoreduction followed by adjuvant chemotherapy. Borderline tumours are managed like malignant epithelial tumours.

Surgical treatment

The treatment, diagnosis, and staging of ovarian cancer is surgical, either by laparotomy or in some cases, laparoscopy. Frozen section is performed during the operation, and the information is used to help determine the diagnosis and stage of the tumour, and therefore the extent of the surgical procedure.

The standard staging procedure is total hysterectomy with bilateral salpingo-oophorectomy with pelvic and paraaortic lymph node dissection and omentectomy. Peritoneal cytology is also acquired by peritoneal washing.

The upper abdomen, peritoneal surfaces, mesenteries, and other abdominal organs are inspected visually. If metastases are evident during surgery, they’re removed as much as possible.

In cases of mucinous epithelial ovarian cancer, some experts advocate removal of the appendix, even though it appears normal visually. This is because mucinous ovarian cancer is associated with appendiceal metastasis.

In young patients with stage Ia disease or non-epithelial ovarian cancers who desire it, fertility-preserving surgery may be performed instead. This includes unilateral salpingo-oophorectomy, peritoneal washing, omentectomy, and pelvic and paraaortic lymphadenectomy.

Cytoreduction (removing as much as possible of visible lesions) may be performed in stage III and IV when complete resection is impossible.

Chemotherapy

Epithelial ovarian cancer is chemosensitive. Neoadjuvant and/or adjuvant chemotherapy is therefore widely used. Chemotherapy is mostly platinum-based, for example carboplatin + paclitaxel. It may sometimes be administered intraperitoneally.

Targeted molecular therapy

All patients with epithelial ovarian cancer should be tested for familial cancer syndromes which may cause ovarian cancer, especially familial BRCA1 and BRCA2 mutations. In cases of epithelial ovarian cancers in people with positive familial BRCA mutations, PARP inhibitors may be used as adjuvant therapy in addition to chemotherapy.

Bevacizumab (anti-VEGF) may also be used.

Radiotherapy

Radiotherapy is not part of the standard management of ovarian cancer, but it may be used on a palliative indication for recurrent or metastatic ovarian cancer.