Back To Medical School November 2006 A Simple Guide to Ovarian Cancer

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Back To Medical SchoolNovember 2006A Simple
Guide to Ovarian Cancer

• Mr Nicholas Myerson
• Consultant Obstetrician Gynaecologist
• Bradford Royal Infirmary

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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Things should be made as simple as possible, but
not any simpler

• Albert Einstein

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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The Female Pelvis
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The Ovary

• In young women 3 x 1.5 x 1.5 cm
• almond shaped
• whitish pink colour
• Post-menopausal women
• 1.5 x 1 x 1cm
• Size and appearance may be altered by
• medication
• pathology

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Ovarian Structure

• Ovarian surface is lined by single-layer germinal
  epithelium
• Tunica albuginea (dense connective tissue)
• Thick outer cortex connective tissue
• follicles
• Central medulla vascular connections
• connective tissue

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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Types of Ovarian Tumour

• There are gt 30 types of ovarian tumour
• Benign or Malignant ( Borderline)
• Cystic or Solid
• Classified by morphological/histological features
  of the tumour
• The ovary contains numerous types of cell
• The classification relates the cell types and
  patterns of the tumour to the cells normally
  present

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Tumour Classification

• Epithelial tumours (90)
• benign, borderline, malignant
• Sex Cord stromal tumours (5)
• Germ Cell tumours (3)
• Lipid Cell tumours
• Gonadoblastoma
• Unclassified
• Metastatic (1)

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Origins of Ovarian Tumours

• Epithelial tumours arise from the surface
  epithelium of the ovary
• Germ cell tumours arise from the follicles or
  germ cells
• Sex cord tumours arise from the stromal and
  associated connective tissue cells
• Metastatic tumours are usually form a gastric or
  a breast primary

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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Epidemiology

• More common in developed areas
• Approx 7000 new cases per year in UK (2.5)
• Lifetime risk in the UK of
• ovarian Ca 1.4
• cervical Ca 1.25
• endometrial Ca 1.1
• breast Ca 1.7
• Peak age for diagnosis is 55-65
• 4th commonest cause cancer death in UK women
  (4500 deaths per year)

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Incidence by Tumour Type

• Epithelial tumours make up 90 of ovarian cancers
• Most common in or post climacteric 50 found in
  45-65 age group
• Sex cord tumours most common in post-menopausal
  women but some sub-types peak in 25-30 year age
  group
• Germ cell tumours have bimodal distribution one
  peak 15-21 year olds and one peak at 65-69.

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Aetiology Non-Epithelial Tumours

• There are no unequivocally identified factors
  associated with the development of germ cell
  tumours
• Parity is reversely correlated with the risk of
  sex cord tumours

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Epithelial Tumours

• These are adenocarcinomas of the ovary
• There are six or more subtypes
• The exact subtype may have an effect on
  presentation and outcome. However the
  epidemiology characteristics are broadly shared
• Several aetiological factors are known

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Tumour Grade

• Histological cell type is not of prognostic
  significance
• Tumour grade is of significance
• Poorly differentiated tumours tend to have a
  worse prognosis especially in early stage disease

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Aetiology of Epithelial Tumours

• Several aetiological factors are well known
• Age (over 50 years) this is a key reason for
  oophrectomy at time of hysterectomy
• Number of lifetime menstrual cycles
• Nulliparity (parity gives increasing protection
  up to Para 4)
• Use of oral contraceptive pill is protective
• Prolonged ovulation induction treatment

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Genetic Factors

• Familial history is highly relevant
• Woman with 2 affected 1st degree relatives has
  25-50 lifetime risk
• Breast/ovarian cancer (BRCA 1 2 genes)
• a woman with BRCA 1 has 50 chance of carcinoma
  before the age of 70
• Hereditary site specific ovarian cancer
• Lynch II syndrome

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Screening for Ovarian Cancers

• No suitable test for population screening
• USS combined with blood tests still has low
  sensitivity specificity
• May be offered to high risk women
• Trials of screening still ongoing
• Genetic screening for women in high risk families
  is most useful to exclude presence BRCA mutations

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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Presentation of Ovarian Cancer

• Ovarian cancer frequently presents at a late
  stage
• Symptoms are often very vague or entirely absent
  until disease is advanced
• This late presentation accounts for poor outcomes
• Early stage disease most often found by chance or
  in high risk patients

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Possible Symptoms

• Localised symptoms include
• abdominal/pelvic/back pain/discomfort
• presence of a mass
• abdominal distension
• abnormal bleeding
• hormonal type changes
• Presentation may be with metastatic lesions
• Weight loss, anaemia and cachexia are common late
  symptoms

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Investigations of Suspected Ca

• Two key tests CA125
• Pelvic USS/TVS
• There are other tumour markers which may be used
  may be present for specific lesions CEA
  CASA Inhibin 1
• Blood Tests FBC, UE, LFTs,
• Other imaging methods MRI CT
• Ascitic Tap
• Surgery / Biopsy

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A Word About Cysts on USS

• Cysts are common and may cause concern
• In young women
• rarely cancerous unless solid/specific
  features
• Cysts are frequent incidental findings
• Cysts under 5cm usually not problematic
• Dermoid cyst (germ cell tumour) is relatively
  common in young women but has typical USS
  features

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A Word About Cysts on USS

• In peri/post menopausal women
• if a cyst is present, a CA125 should be done
• simple cysts lt5cm are rarely malignant
• normal CA125, risk malignancy is lt3
• -conservative management
• Larger cysts, USS appearances, abnormal bloods,
  high risk patient these are managed by
  Gynaecological Oncologists

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Non-Epithelial Cancers

• Presentation is often late
• May present with pelvic mass
• Otherwise, not dissimilar to presentation of
  epithelial lesions
• Imaging may discriminate type of cancer but this
  is often only indicated by histology

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Objectives

• Review the anatomy of the ovary
• Define the classification/types of ovarian cancer
• Outline the incidence and aetiology of the main
  ovarian cancers
• Discuss the presentation and diagnosis of ovarian
  cancers
• Consider the management and outcomes of ovarian
  cancer

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Staging of Epithelial Cancer

• Stage I confined to the ovaries
• Stage II disease confined to the pelvis
• Stage III spread to abdominal organs
• Stage IV spread to distant sites
• Recurrent return after previously treated
• Staging often completed at laparotomy
• Stage is correlated to survival rates

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Management

• Surgery used in vast majority of women
• Mainstay of both diagnosis and treatment
• Exploration (staging) of whole abdomen
• Peritoneal washings / sample ascitic fluid
• Biopsy of suspicious areas
• Therapeutic objective of surgery is the removal
  all tumour
• Chemotherapy
• Palliative radiotherapy in late stage disease

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Stage I Disease

• Usually TAH, BSO, omentectomy, lymphadenectomy
• If very early Stage I, may need nothing more
• Others get adjuvant therapy chemotherapy
• When fertility is required, modified surgery
  retaining unaffected ovary uterus possible but
  there is high risk of relapse
• TAH BSO after childbearing complete

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Stage II Disease

• Usually TAH, BSO, omentectomy, lymphadenectomy
• Adjuvant therapy chemotherapy
• For epithelial cancer, adjuvant therapy is the
  rule
• Radiotherapy little used now
• side effects
• no benefit compared to chemotherapy

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Stage III IV Disease

• TAH, BSO, omentectomy, lymphadenectomy not always
  possible (25)
• However remains optimal procedure
• Need for fully trained surgical team
• Bowel /- bladder involvement
• Maximal debulking of tumour mass/deposits
• Post-operative courses chemotherapy

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Chemotherapy

• Post-operative to prolong remission/survival
• Palliation in advanced/recurrent disease
• Commenced soon after surgery (lt6 weeks)
• Usual range of side-effects
• Typically 4-6 treatments 4 weekly
• Newer agents and regimes developed over last 5-10
  years
• 1st 2nd line regimes

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Chemotherapy Regimes

• NICE guidance
• 1st Line
• Platinum based (cis or carboplatin)
• or Paclitaxil (Taxol) Platinum agent
• 2nd Line
• Re-challenge chemotherapy
• Single agent
• Combination regimes
• Role intra-peritoneal treatment uncertain

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Survival Rates

• 5 year survival rates by stage
• Early stage I 90
• Later stage I 80
• Stage II 65
• Stage III 27
• Stage IV 10
• Cancer grade (1-3) may also play a role

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Follow Up

• For 5-10 years
• Initially more frequent, then 6 monthly
• Recurrence may be indicated by symptoms
• CA125 tends to be raised in recurrence, but this
  may occur late
• Imaging USS
• CT
• MRI