Ovarian Cancer
Ovarian cancer is a heterogeneous group of malignancies arising from the ovary, fallopian tube, or peritoneum, with epithelial cancers being the most common type. It often presents late because early symptoms are vague and non-specific, making recognition of red flags and referral pathways especially important.
Updated UKMLA guide to ovarian cancer, based primarily on NICE guideline: types, risk factors, clinical features, referral criteria, diagnosis, and management.
Histology
There are 3 main histological categories of ovarian cancer:
| Primary category | Sub-categories | Relevant features / description |
|---|---|---|
| Epithelial cancers (tubo-ovarian / primary peritoneal) |
|
Most common category of ovarian cancer
Most likely site of origin: distal fallopian tube |
| Germ cell tumours |
|
Arises from reproductive cells
Typically presents in young females (<30 y/o) Often secrete hormones and tumour markers, including hCGHuman chorionic gonadotropin, AFPAlpha-fetoprotein, LDHLactate dehydrogenase |
| Sex cord-stromal tumours |
|
Tend to present in a younger age group
Often characterised by symptoms related to excessive hormone production |
Causes and Risk Factors
| Category | Risk factors |
|---|---|
| Hereditary and genetic |
|
| Reproductive and hormonal factors | Factors that increase the number of lifetime ovulations:*
Rationale: each ovulation causes repetitive trauma to the ovarian surface epithelium → cellular repair and proliferation → increase risk of DNA damage HRTHormone replacement therapy also increases the risk – not through ovulation, but via direct hormonal effects on the ovarian and fallopian tube epithelial cells |
| Environmental factors |
|
Conversely, factors that reduce the number of lifetime ovulations would be protective against ovarian cancer:
- COCPCombined oral contraceptive pill
- Multiparity
- Breastfeeding
- Giving birth at an older age
Clinical Features
Clinical features of ovarian cancer vary a lot depending on the histological category:
| Ovarian cancer category | Clinical features and presentation |
|---|---|
| Epithelial cancer (tubo-ovarian / primary peritoneal) | Patients frequently present with vague, non-specific symptoms that are often misattributed to IBSIrritable bowel syndrome, menopause, or endometriosis
Symptoms:
Signs:
|
| Germ cell tumours | Typically present in young females (<30 y/o)
|
| Sex cord-stromal tumours | Typically presents in younger patients
|
Ovarian cancer has a very poor prognosis and a high mortality rate, as it is clinically occult and is often diagnosed at an advanced stage. The 5-year overall survival rate for ovarian cancer in the UK is ~45%.
Red Flags and When to Refer (Primary Care)
The following applies to ANY individual with female reproductive organs (including women, trans men, and non-binary people).
If ovarian cancer is clinically suspected, the patient may require either 1) immediate suspected cancer pathway referral or 2) primary care investigations to guide further management, depending on the presenting red flags and clinical findings.
1. Immediate Suspected Cancer Pathway Referral
Suspected cancer pathway referral is indicated in the presence of:
- Ascites, and/or
- Pelvic or abdominal mass (which is not obviously uterine fibroids)
2. Primary Care Investigations
Step 1 – When to Investigate
3 scenarios that warrant primary care investigations for ovarian cancer:
| A | Any of the following persistent / frequent symptoms (esp. >12 times per month and in those who are ≥50 y/o)
|
| B | ≥50 y/o with new-onset IBSIrritable bowel syndrome-suggesting symptoms within the past 12 months
Rationale: IBS rarely present for the 1st time at this age |
| C | Consider carrying out tests in patient reporting ANY of the following:
|
Step 2 – Primary Care Investigations
The choice of initial test and subsequent actions depends on the patient’s age:
| Patient’s age | Initial test | Subsequent steps |
|---|---|---|
| <40 y/o | Urgent ultrasound of the abdomen and pelvis
CA125 is NOT an accurate indicator of ovarian cancer risk in younger patients |
If the ultrasound scan suggests ovarian cancer → suspected cancer pathway referral |
| ≥40 y/o | Measure serum CA125 | If CA125 is elevated (above the age-specific threshold Age-specific threshold from NICE:
If the ultrasound scan suggests ovarian cancer → suspected cancer pathway referral |
5 ultrasound findings that suggest an ovarian mass could be malignant:
- Multilocular cysts (cysts with multiple chambers or compartments)
- Solid areas within the lesion
- Ascites
- Bilateral lesions
- Evidence of metastases
If the ultrasound is normal, or CA125 not meeting the age-specific threshold Age-specific threshold from NICE:
, NICE recommends:
- Identify any other potential causes and investigate as appropriate, and
- If no other cause is identified → advise to return to the GP if symptoms become more frequent and/or persistent
Investigation and Diagnosis (Secondary Care)
| Step | Investigations |
|---|---|
| 1 | If not already completed in primary care, ensure the following are performed:
For those <40 y/o, also measure additional tumour markers (AFP and beta-hCG)
|
| 2 | CT abdomen, pelvis +/- thorax to establish the extent of the cancer (to allow staging) |
| 3 | Pre-treatment tissue biopsy for histology is NOT routinely required for all patients
|
Do not use MRI routinely for assessing women with suspected ovarian cancer.
NICE recommends using the RMI IRisk of malignancy index I score to guide referral to specialist MDT
- RMI IRisk of malignancy index I combines 3 pre-surgical investigation findings
- Ultrasound findings (1 point for each malignant-suggesting feature
NICE outlined 5 malignant-suggesting features:
- Multilocular cysts
- Solid areas
- Metastases
- Ascites
- Bilateral lesions
- Menopausal status (post-menopausal score higher)
- Serum CA125 level (in IU/mL)
- Ultrasound findings (1 point for each malignant-suggesting feature
- Refer to specialist MDT if RMI IRisk of malignancy index I score ≥250
The RMI IRisk of malignancy index I score does NOT predict prognosis or survival of ovarian cancer; it simply helps determine the appropriate surgical team preoperatively. [Ref]
It is unlikely that one would be expected to memorise the full RMI I score calculation and referral thresholds. If anything, it is sufficient to be aware of the score components and their purpose.
It is worth noting that BGCS guidance differs from NICE CG122. BGCS advises that RMI should no longer be used as a triage tool in clinical practice because of its limited sensitivity and specificity, particularly in premenopausal women. Instead, BGCS strongly recommends replacing RMI with the newer IOTA-ADNEX risk model.
Management
| Clinical stage | Corresponding FIGO stage | Management principles |
|---|---|---|
| Early-stage | Stage I (tumour limited to the ovaries or fallopian tubes) | Offer surgery to remove all visible disease and assess the extent of spread, which involves a midline laparotomy with:
Adjuvant platinum-based chemotherapy (e.g. carboplatin) is only necessary for high-risk diseases (grade 3 or stage 1c) to prevent recurrence |
| Advanced-stage | Stage II-IV (tumour spread beyond the ovaries and fallopian tubes | There are 2 treatment paths to achieve complete resection of all macroscopic disease:
1st line chemotherapy: paclitaxel + platinum-based compound (carboplatin or cisplatin) |
In advanced stage 3 and 4 disease, targeted therapy is recommended after completion of chemotherapy. The choice of targeted therapies depends on biomarkers:
- BRCA mutation +ve → olaparib (PARP inhibitor)
- HRD +ve → olaparib + bevacizumab
- BRCA mutation -ve → niraparib, rucaparib (PARP inhibitor)
Full FIGO Staging
The FIGO classification is included for reference and completeness.
|
Stage
|
Description
|
|---|---|
|
I
|
Tumour limited to the ovaries or fallopian tubes
|
|
IA
|
Tumour limited to one ovary (capsule intact) or fallopian tube; no tumour on ovarian or fallopian tube surface; no malignant cells in ascitic fluid or in peritoneal washings
|
|
IB
|
Tumour limited to one or both ovaries (capsule intact) or fallopian tubes; no tumour on the surface of ovary or fallopian tube; no malignant cells in ascitic fluid or in peritoneal washings
|
|
IC
|
Tumour limited to one or both ovaries or fallopian tubes, plus any of the following:
|
|
II
|
Tumour involving one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or peritoneal cancer
|
|
IIA
|
Extension and/or implants on the uterus, fallopian tubes, and/or ovaries
|
|
IIB
|
Extension and/or implants on other pelvic intraperitoneal tissues
|
|
III
|
Tumour involving one or both ovaries or fallopian tubes or peritoneal cancer with microscopically confirmed peritoneal metastases outside the pelvis and/or metastasis to the retroperitoneal lymph nodes
|
|
IIIA1
|
Positive retroperitoneal lymph nodes only (histologically proved):
|
|
IIIA2
|
Microscopic extrapelvic (beyond the pelvic brim) peritoneal involvement, with or without positive retroperitoneal lymph nodes
|
|
IIIB
|
Macroscopic peritoneal metastases that extend beyond the pelvis and that are ≤ 2 cm in largest dimension, with or without positive retroperitoneal lymph nodes
|
|
IIIC
|
Macroscopic peritoneal metastases that extend beyond the pelvis and are > 2 cm in largest dimension, with or without metastasis to retroperitoneal lymph nodes (includes extension of tumour to the capsule of the liver and spleen without parenchymal involvement of either organ)
|
|
IV
|
Distant metastases, excluding peritoneal metastases
|
|
IVA
|
Pleural effusion with positive cytology
|
|
IVB
|
Parenchymal metastasis and/or metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity)
|
References
NICE guideline Ovarian cancer: recognition and initial management
NICE guideline Suspected cancer: recognition and referral. 1.5 Gynaecological cancers
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