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Ovarian cancer - Dr Deac Pimp

Definition

  • Malignant change to the ovaries

 

Risk factors

  • Age (53% diagnosed over 65)
  • Lifestyle accounts for approx. 21% of cases:
    • Smoking (accounts for approx. 3% of cases)
    • Obesity
    • Asbestos exposure
    • Possibly talcum powder use – not well established
    • Lack of exercise
  • Previous ovarian or breast cancer
  • Endometriosis
  • Use of infertility drugs eg clomifene
  • Unopposed oestrogen:
    • HRT – significant increased risk after 5 years of use. Accounts for approx. 1% of cases
    • Early menarche
    • Late menopause
    • Nulliparity or gravida <3
  • Genetic factors:
    • Only 3% of cases occur in those with any kind of genetic predisposition
    • First degree relative with ovarian cancer increases risk by approx. 3 times
    • BRCA1 increases risk to 65%
    • BRCA2 increases risk to 25-35%
    • HNPCC increases risk to 10-12%
  • Protective factors are anything which prevents ovulation:
    • High parity
    • Late menarche/early menopause
    • COC
    • Breastfeeding
    • Tubal sterilisation
    • Hysterectomy +/- salpingectomy

 

Differential diagnoses

  • Causes of a mass:
    • Benign ovarian mass or cyst
    • Fibroids
    • Other pelvic malignancy
    • Secondary malignancy
  • Causes of altered bowel habits/bloating/pelvic pain:
    • IBS
    • IBD
    • Constipation
    • Gastroenteritis
    • Coeliac disease
    • Diverticular disease
    • PID
  • Endometriosis
  • Causes of ascites:
    • Cirrhosis

 

Epidemiology

  • 5th most common cancer in women
  • Leading cause of gynaecological cancer deaths
  • Lifetime risk is 1 in 70
  • 21% present with advanced stage, as early disease is asymptomatic or non-specific
  • 35% 10 year survival

 

Aetiology

  • Not well understood, thought to be related to the constant changes involved in incessant ovulation increasing the chance of a malignant change
  • May be a result of exposure to gonadotropin stimulating hormone

 

Clinical features

  • Are varied and non-specific, should be mindful of ovarian cancer in any of the following presentations:
  • Abdominal mass, sometimes painful
  • Bloating and change in bowel habits
  • Ascites/abdominal distension
  • Early satiety
  • Urinary frequency or urgency
  • Abnormal bleeding patterns
  • Systemic symptoms:
    • Weight loss
    • Fatigue
    • Anorexia

 

Pathophysiology

  • Are many types of ovarian cancer, which affect different demographics and have different management plans and prognoses
  • Epithelial tumours:
    • Most common – make up 90%
    • Most common >50 years
    • Arise from epithelial cells of the ovary
    • Are several sub-types:
      • Serous: are the most common, peak prevalence in age 40-60
      • Endometrioid: account for 20%, peak prevalence 50-70, 5% are associated with endometriosis
      • Clear cell: account for 6%, peak prevalence from age 40, 50% associated with endometriosis
      • Mucinous: account for 10%, peak prevalence age 30-50
      • 15% don’t fit into any category
  • Germ cell tumours:
    • Account for 5-10% of ovarian tumours
    • Most common in <35
    • Have higher survival/cure rate, partly because they present earlier, with rapidly enlarging mass, which often ruptures or tortes
  • Sex cord-stromal tumours:
    • Account for <5% of ovarian tumours
    • Arise from connective tissue
    • Subgroups include:
      • Fibroma
      • Fibrosarcoma
      • Granulosa cell
      • Sartoli-Leydig

 

Investigations

  • CA-125 (although this will miss up to 50% of early tumours)
    • >35 = referral for USS, although may refer if high suspicion with normal CA125
    • Other causes of raised CA125:
      • Endometriosis
      • PID
      • Pregnancy
      • Torsion/rupture of ovarian cyst
      • Other malignancy
      • Heart failure
  • 2 week referral for USS in any abdominal/pelvic mass that isn’t obviously fibroids
  • 2-week referral for anyone presenting frequently with:
    • Abdominal distension/bloating
    • Urinary frequency/urgency
    • Early satiety/anorexia
    • Pelvic/abdominal pain
    • Increase suspicion with age
  • Investigate for ovarian cancer if new-onset IBS over the age of 50
  • Investigate if unexplained weight-loss, fatigue, change in bowel habits
  • Pelvic and abdominal USS
  • If USS suggestive of cancer, CT and/or MRI to establish spread and aid in staging
  • Can use Risk Malignancy Index 1 to assess for risk:
    • Menopausal x CA125 level x USS score
    • Menopausal: 1 = premenopausal, 3 = postmenopausal
    • USS score: multilocular cyst, solid areas, ascites, abdominal metastases, bilateral cysts. Each scores 1, with max of 3

 

Management

  • Appropriate management and aims of treatment vary depending on type and stage of disese
  • Surgery:
    • This is often recommended, even if for palliative control of symptoms
    • In early disease: hysterectomy + bilateral salpingo-oophorectomy is recommended with adjuvant chemotherapy. In women wanting to preserve fertility, a unilateral salpingo-oophorectomy can be considered, but outcomes and chance of relapse are unknown
    • In later disease: debulking of tumour to reduce symptoms + chemotherapy
  • Chemotherapy:
    • Recommended after surgery for all cases stage 2 to 4
    • Intra-peritoneal chemotherapy may be an option
    • Biologicals are being developed eg bevacizumab and olaparib, but aren’t NICE approved currently
  • CA125 is used to monitor treatment and relapse

 

Prognosis

  • 10 year survival is 35%
  • 5 year survival is 46%
  • 1 year survival is between 97% (stage 1) and 51% (stage 4)
  • Highest survival under age 40
  • Survival has doubles over last 40 years
  • No evidence that screening programs significantly reduce mortality
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