Slide 1

Report
Ovarian Cancer
Tim Broadhead
Consultant Gynaecologist & Gynaecological Oncologist
Ovarian Cancer
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Introduction
Pathology
Aetiology
Staging
Symptoms & Examination
Tests
Treatment
Future Developments
Introduction
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6700 cases in UK each year
5th commonest cancer in women
Lifetime risk 1 in 48
Higher incidence in postmenopausal
women
Introduction
Poor prognosis & rarely cured
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4300 die each year
Leading cause of death from
gynae cancer
Advanced disease at
presentation
Median PFS ~1 to 2 years
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Median OS ~ 2.5 years
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5yr survival ~ 30%
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80
Survival (%)
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100
60
40
20
0
0
2
4
6
8
Time (years)
1090 patients
Leeds Cancer Centre 1990-2005
10
Pathology
• Ovarian cancer subtypes
– Epithelial (90%)
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Serous
Endometrioid
Mucinous
Clear cell
– Germ cell tumours (10%)
– Sex-cord stromal cell
tumours (rare)
• Primary peritoneal cancer
Aetiology
Most cases sporadic
• “Incessant Ovulation Theory”
• Pregnancy / COCP protective
• Diet
• Animal fat / Galactose / Alcohol
• Environmental factors
• Talc exposure
• Hysterectomy / Tubal Ligation
Aetiology
Hereditary 5-10%
Breast / Ovarian Cancer Syndrome
• BRCA1 (up to 60% lifetime risk)
• BRCA2 (up to 25% lifetime risk)
• Tumour suppressor genes
HNPCC syndrome
• Mutations of mismatch repair genes
FIGO Staging
• I – confined to ovary
• II – confined to pelvis
FIGO Staging
• III - abdominal extension or lymph
nodes
• IV - distant metastases
Staging
• Importance of stage
• 5 year survival
100
Stage 1& 2
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20%
Survival (%)
80
60
Stage 3 60%
Stage 1 - 90%
Stage 2 - 65%
Stage 3 - 35%
Stage 4 - 10%
Stage 4
40
20%
20
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0
2
4
6
Time (years)
8
10
1090 patients
Leeds Cancer Centre 1990-2005
Symptoms
“Silent Killer”
•1 case every 5
years
•1 every 25,000
consultations
Symptoms
“Ovarian cancer is not silent, rather its
sound is going unheard”
Symptoms
Earlier diagnosis and correct pathway sooner improved survival?
Symptoms
• Carry out tests if any of the following on a
frequent basis – more than 12 times a
month (esp if >50 years old)
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Persistent abdo distension
Feeling full, loss of appetite or both
Pelvic or abdo pain
Increased urinary urgency, frequency or both
Symptoms
• Carry out appropriate tests for ovarian
cancer in any woman of 50 or over who
has experienced symptoms within the last
12 months that suggest irritable bowel
syndrome (IBS)
“ITS NOT IBS, ITS OVARIAN CANCER”
Symptoms
• Consider tests if:
• Unexplained weight loss
• Fatigue
• Changes in bowel habit
• Advise any woman who is not suspected
of having ovarian cancer to return to her
GP if her symptoms become more
frequent and/or persistent
Examination
• Abdo / pelvic examination
• Ascites
• Abdo mass
• Pelvic mass
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Refer the woman urgently if physical examination
identifies ascites and/or a pelvic or abdominal
mass (which is not obviously uterine fibroids)
Which Tests ?
• CA125
• tumour associated antigen
• normal level <35 iu/ml
•  85% epithelial ovarian cancer but also in benign
conditions (fibroids, PID, endometriosis)
•  in only 50% of stage 1 ovarian cancer
Which Tests?
• If CA125 >35 arrange USS abdo / pelvis
Benign
Malignant
First tests in primary care
Measure serum
CA125
35 IU/ml or greater
Ultrasound of abdomen
and pelvis
Less than 35 IU/ml
Normal
Suggestive of
ovarian cancer
Refer urgently
Yes
Investigate
Assess carefully: are other
clinical causes of
symptoms apparent?
No
Advise to return to GP if
symptoms become more
frequent and/or persistent
Detection in primary care
Ascites and/or
pelvic or
abdominal
mass
GP assesses symptoms
Tests in primary care
Suspicion of ovarian cancer
Urgent referral: assessment in secondary care
Support and information
Women presents to GP
Establishing the diagnosis
• CT scan
Complex pelvic mass
Omental cake
Liver surface deposits
Establishing the diagnosis
• Discuss in MDT
• Suspected early stage disease → local cancer unit
• Advanced disease → cancer centre
Treatment of
Early Ovarian Cancer
Surgery
• Suspected early stage disease
Staging Laparotomy
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TAH / BSO
Infracolic omentectomy
Pelvic / PA node sampling
Peritoneal washings
Biopsies of peritoneum
Fertility sparing surgery
Laparoscopic surgery
Surgery
Staging
• Stage important in prognosis and treatment
100
Stage 1& 2
• 5 year survival
20%
Survival (%)
80
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60
Stage 3 60%
Stage 4
40
20%
Stage 1 - 90%
Stage 2 - 65%
Stage 3 - 35%
Stage 4 - 10%
20
0
0
2
4
6
Time (years)
8
10
1090 patients
Leeds Cancer Centre 1990-2005
Treatment of
Advanced Disease
Surgery or
Primary Chemotherapy?
Surgery for advanced disease
• “Debulking surgery”
• Complete debulking - aim to leave no
macroscopic disease
• Optimal debulking <1cm
• Bowel resection / stoma / splenectomy /
peritoneal stripping / pelvic & PA
lymphadenectomy
Surgery for advanced disease
MDT review
•Disease considered resectable
•Medically fit
→ debulking surgery
Surgery
• Volume of residual disease directly determines
survival
• Optimal debulking
– 39 months (median survival)
• Sub-optimal debulking
– 17 months (median survival)
• Surgical skill or tumour biology?
“Inoperable disease”
Neoadjuvant Chemotherapy and
Interval Debulking Surgery
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Disease not resectable
Medically unfit
Scan guided core biopsy
3 cycles chemo → IDS → 3 cycles chemo
Neoadjuvant Chemotherapy and
Interval Debulking Surgery
• Future standard of care?
• Reduced morbidity and mortality
• Results of CHORUS awaited
Chemotherapy
Early stage disease
Early stage disease
• Stage I & II
Died
Alive
Early stage disease
• Stage I & II
– Adjuvant Chemotherapy - Increase chance of cure
Died
Cured by chemo
Alive
ICON1/Action: JNCI 2003
Early stage disease
• Current practice
– Likely benefit
• Stage 1c or higher
• Grade 3
• Clear cell histology
– Uncertainty
• Peri-operative rupture (surgical 1c)
• Inadequate staging
– Chemotherapy vs repeat staging procedure
Chemotherapy
Advanced disease
Chemotherapy
• Stage III & IV disease
– Control cancer
– Prolong life
– Improve symptoms
Palliative
– First line
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Highly effective
70-80% response rate
Median Progression Free Survival 1-2 years
Median Overall Survival 3 years
30% 5 year survival
Some long term survivors
Epithelial Ovarian Cancer
• First-line chemotherapy
– Carboplatin & Paclitaxel
• 6 cycles - 3-weekly
– Carboplatin & Paclitaxel
• 18 weeks - weekly (low dose)
– Carboplatin
• 6 cycles - 3-weekly
Chemotherapy
• Side effects
– Fatigue
– Nausea & vomiting
– Myelosupression
• Anaemia, risk of infection
– Hair loss
– Neuropathy
– Mucositis
– Skin & nail changes
– Allergic reactions
Future Developments
• Prevention
• Risk reducing surgery for BRCA mutations
• Reduced to 1% (PPC) / Breast Ca reduced 50%
• Screening for early disease
• Unknown
• Awaiting results of UKTOCSS / UKFOCSS
• Surgery
• Ultra-radical or IDS
Future Developments
• Chemotherapy
• Improved systemic therapy
– Increased dose intensity
– Biological agents e.g. VEGF inhibitors
• Improved therapy delivery
– Intraperitoneal chemo
Future developments
• Intra-peritoneal chemotherapy
• Suggestion of improved survival
• Increase in side effects
Summary
• Poor prognosis due to late presentation
• Early disease curable
• Advanced disease treatable but not
curable
Summary
• Will NICE guidelines make any difference?
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Investment in additional tests in primary care
Increase in referrals to secondary care
Improved outcomes due to earlier diagnosis?
Less likely to present with advanced cancer?
Reduced referrals to other specialties?
ITS NOT IBS, ITS OVARIAN CANCER!!
Thank You
[email protected]

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