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Ovarian Cancer is the eighth most common cancer in the world. It has a high mortality rate, with 185 000 of the 300 000 detected patients succumbing to the disease in 2018. The prognosis for women with ovarian cancer may be greatly influenced by appropriate first line therapy. So, in a recent CME Talk, Dr Chia Yin Nin, Senior Consultant, Gynaecology and Oncology Specialist, Gleneagles Hospital and Dr Wong Chiung Ing, Senior Consultant, Medical Oncology, Parkway Cancer Centre, highlighted to GPs the updates in ovarian cancer diagnosis and treatment.

Dr Chia first presented the various prediction tools and discussed the appropriateness of surgeries to treat ovarian cancer.

Overview of Ovarian Cancer

The most common form of ovarian cancer is Epithelial Ovarian Cancer (EOC). Known as a “silent killer”, it is asymptomatic in the early stages and only presents vague symptoms (bloating and indigestion) in later stages. As such, it is often misdiagnosed as gastritis.

The peak age group for ovarian cancer is 40-60 years old. Women in the reproductive age group tend to present functional cysts, benign or borderline tumours. Women above 45 tend to present neoplasm (EOC). The majority of cases are sporadic with 5-10% being hereditary, mostly with BRCA mutation. Some cases are caught early at the asymptomatic stage in routine annual check-ups.

Ovarian masses in girls under the age of 20 are usually benign, but some can be germ cell tumours. These are rare and difficult to recognise but increase in size rapidly. Germ cell tumours present with pain and secrete tumour markers aFP, bHCG, LDH.

Not all ovarian masses are cancers. Accurate diagnosis and precise treatment from the start are key to favourable outcomes.

Assessing Malignancy

Dr Chia advises to assess malignancies according to the following steps:

1. Conduct a detailed history and physical examination.

2. Order blood tests for tumour markers CA 125, CA19.9 and CEA. Be aware that markers are only elevated in 50% of early stages of the disease.

3. Request imaging via ultrasound scan, MRI or PET scan.

4. Use combined modalities risk scoring system RMI, ROMA, etc.

She stresses that the most important predictor of malignancy is the age of the patient. The prevalence of benign ovarian cysts is higher in premenopausal women than postmenopausal women. The risk of ovarian cancer in older and post-menopausal women is as high as 1 in 3.

There are various methods that can be used to assess the risk of malignancy in ovarian masses.

Risk of Malignancy Index (RMI)

This is used to calculate the risk with scores of 0, 1 and 3 assigned to certain ultrasound features. The recommended cut-off rate in Singapore to refer a patient to a specialist is 200.

ROMA Testing

This is an improvement over RMI and works on complex algorithms that the lab will calculate for you based on HE4 and CA125 levels and the patient’s menopausal status. However, the CA125 marker is not specific and can be elevated during menses leading to a false result, so do conduct testing when the patient is not menstruating. HE4 is more specific but, like all markers, it can indicate other cancers too. However, overall this method of testing has proven effective, not as a screening standalone but as a guide for GPs to refer patients to specialists.

Ultrasound Scan

In the right hands, this is a reliable method of assessment, and suspicious images should always be referred to a specialist.

MRI and PET Scan

These are not recommended scanning techniques for ovarian cancer as they are not as effective as the aforementioned methods and are more costly.

Surgery for Cancer Staging

The purpose of surgery in the treatment of ovarian cancer is to accurately stage the disease and to optimally debulk the mass. The amount of residual disease correlates with the chances of survival.

The laparoscopic approach for cystectomy should be reserved for women with a relatively low risk of malignancy (premenopausal with a simple cyst and normal ca125). Laparoscopic management of ovarian cysts in postmenopausal women should involve oophorectomy rather than cystectomy. Laparotomy and a KIV full staging procedure by gynae oncologist should be the primary surgery for women who are assessed to be at high risk of malignancy (postmenopausal women with complex cysts and raise CA 125). Laparotomy in such cases will be undertaken through an extended midline incision to ensure appropriate exposure and access.

If the mass turns out to be malignant, up to 30% of early stage cancer can be upstaged to Stage 3 if further surgery is carried out for staging, due to the risk of rupture leading to spillage, which can lead to metastasis in as little as a week.

Treating Ovarian Cancer

Dr Wong continued the presentation with a reminder that the earlier the cancer diagnosis, the greater the probability of recovery. The most common type of ovarian cancer is high grade serous carcinoma, which makes up 70% of ovarian cancer cases.

The appropriate treatments for the respective stages of ovarian cancer are as follows:

1. Stage 1 – If the tumour is confined to the ovaries, surgery is recommended. However, when the tumour is on surface of the ovary, or in the pelvic cavity, adjuvant chemotherapy is indicated. – Survival rate 90%.

2. Stage 2 – The tumour has spread to surrounding structures like the bowel or bladder. Surgery is recommended followed by adjuvant chemotherapy. Survival rate 70%.

3. Stage 3 – The tumour has gone through the lining of the abdomen and may also be in the lymph nodes. About 70-80% of women with ovarian cancer present at stage 3. Surgery is recommended if optimal debulking is possible. Neoadjuvant treatment and maintenance treatment should also be considered. Survival rate 40%.

4. Stage 4 – The cancer has spread to other parts of body. Palliative treatment is offered. Survival rate 20%.

Treatments Pathways for Newly Diagnosed Ovarian Cancer

Dr Wong explained that if the patient’s disease is unresectable, neoadjuvant chemotherapy (chemotherapy before surgery) is recommended. This is usually required when patients present with extensive or bulky ovarian cancer. However, if resection is possible then primary debulking surgery should be done first followed by chemotherapy to control the spread.

Chemotherapy

Chemotherapy is the use of chemical drugs to inhibit tumour cell growth and reproduction. It is a systemic treatment with effects on the primary tumour and cells which may have spread.

Avastin

Malignant tumours need a blood supply to grow. Tumour cells secrete VEGF protein, which stimulates surrounding blood vessels to grow towards them. Armed with a rich blood supply, the tumour grows and multiplies very quickly. Avastin works to block the blood supply to the tumour, causing existing tumour blood vessels to regress and leads to tumour shrinkage.

Intraperitoneal Chemotherapy

This treatment involves infusing a high concentration of anticancer drugs directly into the cancer cells in the abdominal cavity. The side effects including pain, nausea, vomiting and catheter-related complications.

Despite curative intent, the majority of patients with advanced ovarian cancer relapse following first-line multi-modal therapy. Median progression-free survival is 10-18 months and around 70% of women relapse within 3 years of first-line treatment. Only 29% have a 5-year survival rate.

There is a significant need for better frontline treatment to improve outcomes for women with ovarian cancer. There is renewed hope with new targeted drugs called PARP inhibitors.

PARP Inhibitors

Mutations in BRCA1 or BRCA2 proteins carry an increased risk of breast and ovarian cancer. Approximately 1 in 400 women has this mutation and 15-20% of ovarian cancer has the BRCA mutation.

PARP inhibitors are a type of targeted therapy that inhibit the PARP protein in cancer cells to stop them repairing damaged DNA. Without repair, the tumour cells will die. PARP inhibitors have the added advantage of being an oral therapy, and target mainly the cancer cells so have fewer side effects on healthy cells.

Conclusion

Ovarian cancer remains a common cancer with significant morbidity and mortality. The risk of relapse is high despite surgery and adjuvant treatment. However, significant improvements have been made with targeted therapy including PARP inhibitors. These targeted therapies provide new opportunities to build on the benefit of chemotherapy and surgery.