A deep dive into ovarian cancer

05/12/24, 12:22

Insight into the different stages

Intro

Ovarian cancer occurs when abnormal cells in the ovary begin to grow and divide uncontrollably; this may lead to tumour formation. According to Cancer Research UK , there are around 7,500 new cases of ovarian cancer each year - that is around 21 a day. This makes ovarian cancer the 6th most common cancer in females in the UK, as it makes up around 4% of all cancer cases. Nevertheless, a total of around 11% of all ovarian cancer cases are thought to be preventable.

This article aims to provide a comprehensive overview of ovarian cancer including the risk factors, prevention, diagnosis, and treatment.

Diagnostics

At present, there is no screening test specific for ovarian cancer. Hence, this often leads to late-stage diagnosis, which results in death or high rates of recurrence within ten years of initial diagnosis, should remission be reached. Initial diagnostic testing includes transvaginal ultrasonography and serum cancer antigen 125 (CA 125) level testing.

Transvaginal Ultrasonography

This type of imaging is used to assess the overall architecture and vascularity of the ovaries as well as to differentiate cystic from solid masses and detect ascites (a collection of fluid within abdominal spaces). The sensitivity (a tests ability to correctly identify if an individual has a disease) and specificity (a tests ability to correct identify individuals who do not have a disease) for distinguishing malignant lesions using this type of imaging is 86% - 94%.

Blood Testing

Complete blood count, as well as liver function tests, calcium, and serum biomarkers, are often obtained if ovarian cancer is suspected. CA 125 is the most commonly tested biomarker. However, its usefulness in the diagnosis of ovarian cancer depends on the stage of the disease at the time of testing.

CA 125 is elevated in around 80% of epithelial ovarian cancers overall. However, it is only elevated in around 50% of early-stage epithelial ovarian cancers. This biomarker may also rise in conditions such as fibroids and endometriosis. Other biomarkers involved include human epididymis protein 4 (HE4), a glycoprotein expressed in about 1/3rd of ovarian cancers that lack elevated CA125. Biomarkers for non-epithelial cancers include inhibin A/B for sex-cord stromal tumours and serum α-fetoprotein and quantitative human chorionic gonadotropin for germ cell tumours.

Staging

Ovarian cancer is often categorised using the FIGO (1 – 4 staging) system, named after the International Federation of Gynaecological Oncologists.

Stage 1

Stage one ovarian cancer means that the cancer is only located in the ovaries and is further divided into three groups. According to the CRUK website the three groups are:

Stage 1A: the cancer is entirely confined within a singular ovary Stage 1B: the cancer is entirely confined within both ovaries Stage 1C is split into 3 subgroups:

Stage 1C1: the cancer is present in one or both ovaries and the ovary ruptures during a surgical procedure
Stage 1C2: the cancer is present in one or both ovaries and the ovary ruptures before a surgical procedure or there is evidence of cancer on the surface of the ovary
Stage 1C3: the cancer is present in one or both ovaries and cancer cells are detected in the fluid collected from the abdominal cavity during surgery

These groups can be further illustrated in Figure 1 at the end of the text.

Stage 2

Stage 2 ovarian cancer means the cancer has grown outside the ovaries and is growing within the pelvis. It is divided into two groups. According to the CRUK website the two groups are.

Stage 2A: the cancer has extended its growth into either the fallopian tubes or the womb
Stage 2B: the cancer has infiltrated surrounding tissues within the pelvic region such as the bladder or the bowel

These groups can be further illustrated in Figure 2 at the end of the text.

Stage 3

Stage 3 ovarian cancer means the cancer has grown outside the pelvis into the abdominal cavity or lymph nodes. It is divided into three groups. According to the CRUK website the three groups are: Stage 3A is divided into two subgroups:

Stage 3A1: the cancer has infiltrated lymph nodes in the rear of the abdomen
Stage 3A2: there are cancer cells detected in tissue samples taken from the peritoneum, cancer may also be present within the lymph nodes
Stage 3B: Cancerous growths are present on the peritoneum that measure up to 2 cm in size, cancer may also be present within the lymph nodes
Stage 3C: Cancerous growths are present on the peritoneum that measure over 2 cm in size, cancer may also be present within the lymph nodes

These groups can be further illustrated in Figure 3 and Figure 4 at the end of the text.

Stage 4

Stage 4 ovarian cancer means the cancer has metastatic and has spread to organs some distance away from the ovaries. It is divided into two groups. According to the CRUK website, the two groups are:

Stage 4A: the cancer has induced a build-up of fluid in the pleura
Stage 4B: the cancer has infiltrated various locations throughout the body including the interior of the liver or spleen, lymph nodes outside the abdominal region and any other organ within the body These groups can be further illustrated in Figure 5 and Figure 6 at the end of the text.

Types of Ovarian Cancers

There are three known types of ovarian cancer: epithelial, germ cell ovarian tumours and sex cord-stromal tumours.

Epithelial Ovarian Cancer

Epithelial ovarian cancer is the most common type of cancer. According to Cancer Research Uk , about 90% of all ovarian tumours are epithelial. In this type of ovarian cancer, cancer starts in the surface layer covering the ovary. There are four stages of epithelial ovarian cancer - stages 1 to 4.

Type	Summary
High-grade serous tumours	● 90% of all tumour tumours ● 10-year mortality rate of roughly 70%
Low-grade serous tumours	● 10% of all tumour types ● Diagnosed at a younger age; better prognosis than high-grade serous tumours
Endometrioid carcinomas	● Origins linked to endometriosis ● Good prognosis; mostly diagnosed at an early stage and are low-grade
Clear cell carcinomas	● Origins linked to endometriosis ● 10% of epithelial ovarian cancers; rare form ● Often diagnosed in early stages. Late diagnosis has a poor prognosis.
Mucinous carcinoma	● Least common form of epithelial ovarian cancer ● Origins linked with metastasis from gastrointestinal tract

Table 1. Types of epithelial ovarian cancers.

Germ Cell Ovarian Cancers

Germ cell ovarian tumours are rare as they make up only 3% of ovarian cancer cases. They have a younger age of diagnosis with the average age being between 10 and 30 years old. Germ cell ovarian tumours can be benign (non-cancerous) or malignant (cancerous)

Sex Cord-Stromal Tumours

Sex cord-stromal tumours (SCSTs) are rare tumours of the ovary that originate in tissues that support the ovaries, known as the stroma or the sex cords. SCSTs account for around 5% of all ovarian cancer cases and are often diagnosed early. There are three main groups of SCSTs:

Pure stromal tumours such as fibromas and thecomas. These are mainly benign.
Pure sex cord tumours such as adult and juvenile granulosa cell tumours. These are the most common types of SCSTs and are malignant.
Mixed sex cord-stromal tumours such as Sertoli-Leydig cell tumours. These can be either malignant or benign.

Symptoms

Historically, the signs and symptoms of ovarian cancer are non-specific and vague. The most common presenting symptoms in women are:

Swelling or bloating of the abdomen
Feel full quickly when eating
Unexplained weight loss
Pelvic and or abdominal pain or discomfort
Unexplained fatigue
A frequent need to urinate
Changes in bowel habits or IBS symptoms

The most common presenting symptom in children and adolescents is persistent abdominal pain.

However, precocious puberty, irregular periods or hirsutism (excessive hair growth) may also be present.

Due to the non-specific nature of these symptoms, many women will not get them checked by a doctor. It is still vitally important for a person to get any non-typical symptoms checked out by a doctor. Early diagnosis will lead to better outcomes.

Treatment

There are a variety of different treatment options for ovarian cancer. The treatment an individual undergoes is dependent on the size and location of the cancer as well as if it is metastatic.

Debulking Surgery

Debulking is a type of cytoreductive surgery that aims to remove as much cancer as possible if it has spread to areas within the pelvis and abdomen. This type of surgery is a mainstay of ovarian cancer treatment as most cases are more advanced in staging when initially diagnosed. Generally, debulking surgery is used on cancer that has spread widely throughout the abdomen and its goal is to do ‘optimal cytoreduction’, meaning no visible cancer is left behind or, if removing all visible disease is not possible, lesions less than 1cm in size are left.

Hysterectomy

For most women, a hysterectomy is the first-line treatment for ovarian cancer. The surgery removes the womb (including the cervix) as well as both ovaries and fallopian tubes and is known as a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). This procedure is further illustrated by Figure 7 at the end of the text.

Chemotherapy

Chemotherapy is the use of anti-cancer drugs to destroy cancer. These drugs circulate throughout the body via the bloodstream. In the treatment of ovarian cancer, chemotherapy can be given before, during or after surgery. The most commonly used drugs are carboplatin and paclitaxel. However, these are not the only options. Chemotherapy is typically used in the treatment of ovarian cancer if the cancer is:

● Stage 1C or above

● Stage 1A or 1B but is high grade

● Has come back (recurrence)

Medication	Route of administration	Stage treated	Duration
Paclitaxel and carboplatin	Intravenous	I	21 days
Paclitaxel and carboplatin	Intravenous	I	7 days
Docetaxel and carboplatin	Intravenous	I	21 days
Paclitaxel and cisplatin	Intravenous or intraperitoneal	II, III, IV	21 days
Paclitaxel and carboplatin	Intravenous or intraperitoneal	II, III, IV	21 days
Dose-dense paclitaxel and carboplatin	Intravenous	II, III, IV	21 days
Paclitaxel and carboplatin	Intravenous	II, III, IV	7 days
Docetaxel and carboplatin	Intravenous	II, III, IV	21 days
Carboplatin and liposomal doxorubicin	Intravenous	II, III, IV	28 days
Bevacizumab with paclitaxel and carboplatin	Intravenous	II, III, IV	21 days

Table 2. Commonly used chemotherapy drugs for ovarian cancer

Radiotherapy

Radiotherapy involves the use of high-energy X-rays to destroy ovarian cancer cells. It is not the main treatment of ovarian cancer and is often used to try and shrink the size of tumours or to reduce the symptoms of advanced ovarian cancer. This is known as palliative radiotherapy.

Targeted Therapies

Cancer-targeting drugs change how a cell works by acting on cellular processes or by modifying cell signalling. They stimulate the body to attack or control cancer cell growth. These drugs are a form of palliative treatment. The two most common drugs are olaparib and bevacizumab.

Olparib

Olaparib (Lynparza) belongs to a drug type known as cancer growth blockers. It acts on PARP (poly ADP-ribose polymerase); a protein that helps damaged cells repair and regenerate themselves. Olaparib inhibits PARP from working.

Bevacizumab

Bevacizumab (Avastin) belongs to a drug type known as anti-angiogenesis treatments. It targets VEGF (vascular endothelial growth factor) proteins. VEGFs aid in cancer cell growth as they help cancers develop their blood supplies, meaning they can become self-sufficient. Bevacizumab blocks VEGF proteins from working, which cuts off the blood supply that feeds the cancer, ultimately starving it and preventing its growth.

Risk Factors

Modifiable	Nonmodifiable
Smoking	BRCA1 and/ord BRCA2 mutation carrier
Hormone Replacement Therapy (particularly for more than five years)	Family predisposition/history
Obesity	Lynch syndrome
	Endometriosis
	Uninterrupted ovulation cycles
	Ethnicity/race

Table 3. Ovarian cancer risk factors

Genetic Syndromes

Familial genetic syndromes are the strongest known risk factor for the development of ovarian cancers, as they account for around 10% - 12% of all cases. Table 4 which is taken from the paper ‘Diagnosis and Management of Ovarian Cancer’ by Doubeni et al (2016) illustrates genetic syndromes known to have an increased risk of ovarian cancer.

Hereditary Breast and Ovarian Cancer Syndrome (HBOC)

Mutations of the BRCA1 and BRCA2 genes are primarily associated with a genetic risk of developing ovarian cancer and can increase the risk from 1.6% to 40% (BRCA1) and 1.6% to 18% (BRCA2). This syndrome should be considered if a woman has close blood relative with a diagnosis of ovarian or breast cancer by the age of 50.

Lynch Syndrome

Although less common, Lynch syndrome is also linked to the development of ovarian cancer as it is involved in 2% - 3% of cases. Lynch syndrome is an autosomal dominant genetic disorder in which there is a mutation that increases the risk for certain cancers, specifically colorectal cancer, as well as increases the risk for other malignancies.

Ovulation

Ovulation is directly linked to the risk of ovarian cancer. Studies have shown that the more ovulatory cycles a woman has, the higher her risk of developing ovarian cancer. This may be due to the pro-inflammatory response from the distal fallopian tube during ovulation, which is known to promote malignant ovarian tendencies. Assuming this is true, factors that interrupt or prevent ovulation, such as contraception, early onset menses, pregnancy, breastfeeding and early menopause, could decrease a woman’s risk of developing ovarian cancer.

Endometriosis

Endometriosis, a disease in which tissue similar to the uterine lining grows outside the uterus, is known to be linked to some types of epithelial ovarian cancers. Endometriosis-associated epithelial ovarian cancers tend to develop in younger women and have an overall better prognosis.

Where to seek help if affected by this article...

For support and more information regarding ovarian cancer:

Macmillan

Cancer Research

If you or somebody you know have been affected by this article, help is always available:

Mind and Samaritans

Written by Lily Manns