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

Back To Medical School
November 2006
A Simple Guide to
Ovarian Cancer
Mr Nicholas Myerson
Consultant Obstetrician & Gynaecologist
Bradford Royal Infirmary
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
“Things should be made as simple as
possible, but not any simpler”
Albert Einstein
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
The Female Pelvis
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
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
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
Types of Ovarian Tumour
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There are > 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
Tumour Classification
• Epithelial tumours
(90%)
benign, borderline, malignant
• Sex Cord stromal tumours (5%)
• Germ Cell tumours
(3%)
• Lipid Cell tumours
• Gonadoblastoma
• Unclassified
• Metastatic
(1%)
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
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
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)
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 postmenopausal 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.
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
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
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
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
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
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
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
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
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
Investigations of Suspected Ca
• Two key tests:
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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, U+E, LFTs,
Other imaging methods; MRI & CT
Ascitic Tap
Surgery / Biopsy
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
A Word About Cysts on USS
• In peri/post menopausal women
if a cyst is present, a CA125 should be
done
simple cysts <5cm are rarely malignant
normal CA125, risk malignancy is <3%
-conservative management
• Larger cysts, USS appearances, abnormal
bloods, high risk patient – these are managed
by Gynaecological Oncologists
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
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
Staging of Epithelial Cancer
Stage I:
Stage II:
Stage III:
Stage IV:
Recurrent:
confined to the ovaries
disease confined to the pelvis
spread to abdominal organs
spread to distant sites
return after previously treated
• Staging often completed at laparotomy
• Stage is correlated to survival rates
Management
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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
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
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
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
Chemotherapy
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Post-operative to prolong remission/survival
Palliation in advanced/recurrent disease
Commenced soon after surgery (<6 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
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
Survival Rates
5 year survival rates by stage
• Early stage I
• Later stage I
• Stage II
• Stage III
• Stage IV
90%
80%
65%
27%
10%
Cancer grade (1-3) may also play a role
Follow Up
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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