Ovarian Cancer Flashcards
What is the rapid access clinic?
RAC is a one stop service that help triage patients with pelvic masses into those that need referral to a gynae cancer centre & those that can be managed locally
What is epithelial ovarian cancer?
- Epithelial ovarian cancer is a relatively uncommon gynaecological cancer occurring when there is malignant transformation of the ovarian capsule epithelium.
- The epithelium covering the ovary consists of the same epithelial cells that line the peritoneal cavity.
- Thus, epithelial ovarian cancer and primary peritoneal cancer occur via the same pathophysiology and are treated with the same basic principles.
What is the commonest subtype of epithelial ovarian cancer?
High grade serous ovarian cancer (HGSC).
HGSCs make up most ovarian cancer cases and have the lowest survival rates.
What is the percentage of ovarian cancers that present at advanced stage?
Over 70% of ovarian cancers present at an advanced stage, where the disease has already spread outside the ovaries.
What are the symptoms of ovarian cancer?
- Patients often present with vague, non-specific symptoms such as abdominal bloating, early satiety, and dyspepsia (suggestive of upper abdominal disease).
- Other symptoms are more suggestive of pelvic disease, such as pelvic pain, pressure, low back pain, and urinary urgency.
Causes of ovarian cancer
- BRCA1
- BRCA2
- Hereditary non-polyposis colon cancer
- Mutations MSH2 and MLH1 (associated with ovarian cancer)
- Additionally, a precursor lesion was ultimately identified, serous tubal intra-epithelial carcinoma (STIC).
What is the pathophysiology of ovarian cancer?
- Epithelial ovarian cancer does not typically invade into organ space parenchyma, but instead attaches to the surface of organs.
- Tumour cells implant along the lining of the peritoneal cavity (local advancement), bowel mesentery, and liver capsule, indicating metastatic disease.
- Exfoliated cancer cells follow the natural circulation of the peritoneal fluid, along the right paracolic gutter and sub-diaphragmatic space. Thus, the right liver edge and diaphragm peritoneum are common sites of tumour implantation.
- The omentum is also a common site of tumour implants. The initial spread pattern of ovarian cancer is by direct spread or lymphatic drainage.
- Haematogenous dissemination typically occurs late in the disease process.
Hx and exam of ovarian cancer
- A palpable adnexal mass on physical examination can be observed in patients with ovarian cancer.
- Omission of a pelvic examination at the first evaluation of ovarian cancer symptoms is associated with a delay in diagnosis.
- A fixed pelvic mass on examination with nodularity along the recto-vaginal septum may be present in ovarian cancer.
- Often, the presenting symptoms of ovarian cancer are not gynaecological but rather gastrointestinal, such as abdominal bloating, nausea, dyspepsia, early satiety, diarrhoea, and constipation.
- Ascites
- Abdominal distension
Investigations of ovarian cancer
- Pelvic ultrasound- When a pelvic mass is detected on physical examination, transvaginal ultrasound is the preferred imaging modality. Furthermore, ultrasound can characterise the mass (e.g., solid, cystic, complex) and Doppler flow can also be assessed. Ovarian cancers tend to have increased Doppler flow.
- CT scan- If upper abdominal disease is suspected on examination, CT can assess for the presence of these typical findings of advanced disease.
- CA-125- In patients with advanced-stage disease, >80% of CA-125 levels are elevated; however, the test is not diagnostic, as the marker can be elevated as a result of numerous non-malignant (e.g., endometriosis, uterine fibroids, pregnancy, and ovarian cysts) and malignant conditions (e.g., pancreatic, breast, lung, gastric, and colon cancers).
Risk factors of ovarian cancer
Increasing age.
FHx of ovarian cancer and/or breast cancer.
Never used OCP.
BRCA1 and BRCA2 mutations.
Differentials of ovarian cancer
- IBS
- Metastases to the ovary
- Endometriosis
- Diverticular disease
- Meigs’ syndrome- Mainly seen in older women, the triad of ascites, hydrothorax, and a benign ovarian tumour comprises Meigs’ syndrome.
Management of stage 1A/1B or grade 1/2 ovarian cancer
Surgery with staging - Patients with early stage low-risk disease (e.g., stage IA and stage IB) and favourable tumour characteristics (e.g., grade 1 or grade 2) do not require adjuvant chemotherapy.
However, these patients must have undergone appropriate surgical staging including omentectomy, lymph node dissection (pelvic and para-aortic), and staging biopsies.
How should you prepare ovarian cancer patients for surgery?
▪ Perioperative care: patient should consume protein rich meals (help with recovery and growth of healthy cells)
▪ Diabetes is hard to get under control, but hypertension can quickly be rectified
▪ CPET device to determine the likelihood that patients will need high dependency support
▪ Review patient each day to identify problems.
Treatment of early (stage 1C or 1A/1B or grade 3) ovarian cancer
o Surgery with staging- including total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, pelvic and para-aortic lymph node dissection, and staging biopsies are indicated.
o AND chemotherapy- Currently, paclitaxel and carboplatin is the combination regimen of choice
Treatment of advanced (stage 2, 3 and 4) ovarian cancer
o When advanced disease is discovered at surgical exploration, a maximal surgical effort to debulk all tumour deposits is necessary.
o The current standard of care is an attempt to achieve a complete cytoreduction.
o Debulking surgery can occasionally involve bowel resection, diaphragm stripping, and splenectomy.
o For patients with stage II or III disease who undergo optimal debulking surgery (no tumour nodule >1 cm at the completion of surgery), intraperitoneal (IP) chemotherapy with carboplatin and paclitaxel is recommended.
• Platinum-sensitive recurrent disease
o Carboplatin and paclitaxel
• Platinum-resistant recurrent disease
o Doxorubicin liposomal
Monitoring of ovarian cancer
• After completion of first-line therapy, and where no evidence of disease persists either clinically (CT scan or examination) or chemically (CA-125), patients are generally followed with a history, physical examination (including pelvic examination), and optional CA-125 level every 3 to 4 months.
Why is monitoring of CA-125 levels not advised in patients with a hx of ovarian cancer?
• There are data that call into question the clinical benefit of routine CA-125 level testing in patients with a history of ovarian cancer.
There was no difference in survival when patients received chemotherapy ‘early’, based upon a rise in the CA-125 compared with patients who delayed therapy until clinical symptoms developed.
What is risk of malignancy index I score?
RMI I is the risk of malignancy index I. It combines three pre-surgical features: serum CA125 (CA125), menopausal status (M) and ultrasound score (U).
The RMI is a product of the ultrasound scan score, the menopausal status and the serum CA125 level (IU/ml).
RMI I = U x M x CA125
How do you calculate the RMI I score?
The ultrasound result is scored 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites and bilateral lesions. U = 0 (for an ultrasound score of 0), U = 1 (for an ultrasound score of 1), U = 3 (for an ultrasound score of 2–5).
The menopausal status is scored as 1 = pre-menopausal and 3 = post-menopausal.
The classification of ‘post-menopausal’ is a woman who has had no period for more than 1 year or a woman over 50 who has had a hysterectomy.
Serum CA125 is measured in IU/ml and can vary between 0 and hundreds or even thousands of units.
How do you interpret RMI I?
Refer all women with an RMI I score of 250 or greater to a specialist MDT.
What is the percentage of high grade serous ovarian cancers associated with BRCA1 or BRCA2?
15%.
Carrying 1 of these mutations makes it far more likely to develop ovarian & breast cancer than non-carriers.
Why should you do a genetic test in patients with ovarian cancer?
If patient is a carrier , this allows other family members to undergo testing to see if they’re at risk too.
Asymptomatic carriers may elect to undergo prophylactic surgery to reduce risk of breast & ovarian cancer
Which treatment works better in patients with BRCA related tumours?
PARP inhibitors
MoA of PARP inhibitors
Olaparib and other PARP inhibitors inhibits DNA repair within cancer cells. Particularly important in HGSC
