Ovarian tumours and ovarian cancer

Overview

Ovarian cancer is the second commonest gynaecological cancer in the UK and the commonest cause of death among them. It kills because it is silent: symptoms are vague, so about two-thirds present at stage III or beyond. Detected early, it has an excellent outlook.

Most ovarian cancers are epithelial and occur in older women; germ cell tumours affect young women and girls; sex cord stromal tumours make hormones. Secondary deposits from other organs (metastases) often settle in the ovary too. Many high-grade serous "ovarian" cancers actually start in the fallopian tube.

Classification

Only about 3% of ovarian cancers occur before 35.

Epithelial ovarian cancer

Subtypes

Risk factors

Incessant ovulation theory: each ovulation injures the surface epithelium; repeated repair raises the chance of a malignant mutation. Anything that stops ovulation (pill, pregnancy) is protective. High gonadotrophin drive is also blamed.

Genetics

• At least 10-15% of epithelial ovarian cancers are hereditary.
• BRCA1 and BRCA2 (breast-ovarian cancer syndrome): about 90% of hereditary cases; high-grade serous; advanced at presentation; very sensitive to platinum; also breast cancer.
• Lynch syndrome (mismatch repair genes): endometrioid or clear cell, earlier stage, better outcome; also endometrial and bowel cancer.
• Hereditary cancers occur about 10 years earlier than sporadic ones.
• Risk-reducing bilateral salpingo-oophorectomy after the family is complete cuts ovarian cancer risk by about 90% (primary peritoneal cancer can still occur). It is done earlier for BRCA1 carriers (late 30s) than BRCA2 (40s).

Screening

• No proven benefit: screening with TVUSS and CA125 has not improved survival, either in the general population or in high-risk women.

Clinical features

Symptoms are persistent but vague; consider ovarian cancer in any woman over 50 with:

• Abdominal bloating / increased girth (ascites)
• Persistent pelvic or abdominal pain
• Early satiety, poor appetite
• Change in bowel habit, urinary frequency, backache, fatigue, weight loss

Signs:

• Fixed, hard, irregular pelvic mass, often bilateral.
• Ascites (shifting dullness); with a pelvic mass, ovarian cancer is very likely.
• Pleural effusion (stage IV if malignant cells present).
• Omental cake; supraclavicular or groin nodes.

About 20% of adnexal masses before the menopause are malignant, rising to about 50% after it.

Investigations

• Transvaginal (and abdominal) ultrasound: first imaging. Suspicious features: multilocular, solid areas, bilateral, ascites, peritoneal or omental deposits.
• Tumour markers (table below).
• Risk of malignancy index (RMI): combines ultrasound features (U), menopausal status (M) and CA125 (RMI = U × M × CA125) to sort masses into low, intermediate or high risk; high-risk cases go to a gynaecological oncology centre.
• CT chest, abdomen and pelvis for spread and staging; MRI for tissue planes.
• Chest X-ray, FBC, renal and liver function.
• Ascitic or pleural fluid cytology.
• Biopsy (omentum, image-guided or laparoscopic) before neoadjuvant chemotherapy.
• In young women with a solid mass: AFP, hCG, LDH (germ cell markers).

Tumour markers

FIGO staging (surgical)

• At diagnosis: about 25% stage I, 10% stage II, 50% stage III, 15% stage IV.
• Spread: mainly transcoelomic across the peritoneum (omentum, under-surface of the diaphragm), then lymphatic (pelvic and para-aortic), and late by blood.
• Overall 5-year survival is under half (about 46% in the UK).

Management

Surgery

• Done by a gynaecological oncologist in a cancer centre.
• Midline (vertical) laparotomy, peritoneal washings / ascites for cytology, total abdominal hysterectomy + bilateral salpingo-oophorectomy + infracolic omentectomy, peritoneal biopsies, and removal of all visible tumour (cytoreduction or debulking); lymph node dissection in apparent early disease.
• Aim: complete cytoreduction (no visible disease); "optimal" means less than 1 cm left.
• No residual disease after surgery is the most important prognostic factor.
• If complete debulking looks impossible or she is unfit: neoadjuvant chemotherapy (3 cycles), then interval debulking surgery. This is not worse than primary surgery and has fewer complications.
• Fertility-sparing surgery (unilateral salpingo-oophorectomy with staging and endometrial sampling) for young women with stage IA low-grade disease or borderline tumours.

Chemotherapy

• First line: carboplatin + paclitaxel, usually every 3 weeks for 6 cycles.
  • Carboplatin has replaced cisplatin: equally effective, less nephrotoxic and less nausea; dose calculated from GFR.
  • Paclitaxel (from the yew tree; microtubule damage): total hair loss, peripheral neuropathy, neutropenia, hypersensitivity (steroid premedication).
• Low-grade stage IA or IB that is properly staged may not need chemotherapy.
• Maintenance: bevacizumab (anti-VEGF; hypertension, bowel perforation) or PARP inhibitors (olaparib) for BRCA-mutated tumours.
• All women with non-mucinous high-grade cancer are offered BRCA testing.
• Follow-up with examination and CA125; recurrence is usually treated with palliative intent (platinum again if remission lasted over 6 months).

Sex cord stromal tumours

• About 10% of ovarian tumours but about 90% of hormone-producing ones; usually low-grade, unilateral, solid, yellow cut surface; good prognosis.

Treatment: unilateral salpingo-oophorectomy with staging in the young; full surgery in older women; surgery for recurrence (chemotherapy works poorly).

Malignant germ cell tumours

• About 10% of ovarian tumours; young women (and children); often present with a mass, torsion or haemorrhage (about 10%), sometimes in pregnancy.
• About 70% are stage I at diagnosis; excellent cure rates with fertility-sparing surgery, plus platinum-based chemotherapy (such as bleomycin, etoposide and cisplatin) when disease has spread beyond the ovary. Stage I dysgerminoma and low-grade teratoma: surgery alone, over 90% 5-year survival.

Metastatic tumours

• Krukenberg tumour: bilateral ovarian metastases containing mucin-filled signet-ring cells; most often from the stomach (diffuse type), also colon and breast.
• Bilaterality helps separate metastatic mucinous tumours from primary mucinous ovarian cancer, which is usually unilateral.

Quick revision

• Epithelial 80% (high-grade serous most), sex cord 10%, germ cell 10%, plus metastases.
• Risk: nulliparity, BRCA, Lynch, endometriosis; protection: pill (up to 50%), pregnancy, tubal ligation.
• Presents late (two-thirds at stage III or more) with bloating, early satiety, pain, ascites.
• CA125: epithelial, not for screening; AFP: yolk sac; hCG: choriocarcinoma; LDH: dysgerminoma; inhibin: granulosa.
• Staging is surgical; IC = rupture or malignant washings; IIIC = deposits over 2 cm or nodes; IV = malignant pleural effusion or liver parenchyma.
• Treatment: TAH + BSO + omentectomy + debulking, then carboplatin + paclitaxel ×6.
• Dysgerminoma: commonest malignant germ cell tumour, 20% bilateral, radiosensitive.
• Krukenberg: bilateral, signet-ring cells, gastric primary.

Written by The House Job from standard references (Gynaecology by Ten Teachers).

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