1. Tim Broadhead Consultant Gynaecologist & Gynaecological Oncologist
Ovarian Cancer
Tim Broadhead
Consultant Gynaecologist & Gynaecological Oncologist

3. Ovarian Cancer Introduction Pathology Aetiology Staging
Symptoms & Examination
Tests
Treatment
Future Developments

4. Introduction 6700 cases in UK each year 5th commonest cancer in women
Lifetime risk 1 in 48
Higher incidence in postmenopausal women

5. Introduction Poor prognosis & rarely cured 4300 die each year
Leading cause of death from gynae cancer
Advanced disease at presentation
Median PFS ~1 to 2 years
Median OS ~ 2.5 years
5yr survival ~ 30%
1090 patients
Leeds Cancer Centre

6. Pathology Ovarian cancer subtypes Primary peritoneal cancer
Epithelial (90%)
Serous
Endometrioid
Mucinous
Clear cell
Germ cell tumours (10%)
Sex-cord stromal cell tumours (rare)
Primary peritoneal cancer

7. Aetiology Most cases sporadic “Incessant Ovulation Theory” Diet
Pregnancy / COCP protective
Diet
Animal fat / Galactose / Alcohol
Environmental factors
Talc exposure
Hysterectomy / Tubal Ligation

8. 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

9. FIGO Staging
I – confined to ovary
II – confined to pelvis

10. FIGO Staging III - abdominal extension or lymph nodes
IV - distant metastases

11. Staging Importance of stage 5 year survival Stage 1 - 90%
60%
20%
1090 patients
Leeds Cancer Centre

12. Symptoms “Silent Killer” 1 case every 5 years
1 every 25,000 consultations

13. Symptoms
“Ovarian cancer is not silent, rather its sound is going unheard”

14. Symptoms
Earlier diagnosis and correct pathway sooner - improved survival?

15. Symptoms
Carry out tests if any of the following on a frequent basis – more than 12 times a month (esp if >50 years old)
Persistent abdo distension
Feeling full, loss of appetite or both
Pelvic or abdo pain
Increased urinary urgency, frequency or both

16. 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”

17. 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

18. Examination Abdo / pelvic examination Pelvic mass → Ascites Abdo mass
Refer the woman urgently if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids) →

19. 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

20. Which Tests? If CA125 >35 arrange USS abdo / pelvis Benign
Malignant

21. First tests in primary care
Measure serum CA125
35 IU/ml or greater
Less than 35 IU/ml
Assess carefully: are other clinical causes of symptoms apparent?
Ultrasound of abdomen and pelvis
Normal
NOTES FOR PRESENTERS:
Key points to raise: Detection in primary care (see also algorithm on page 7 of the QRG)
This slide relates to the key priorities for implementation about asking the right questions
Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer.
The majority of women with symptoms suggestive of ovarian cancer will not have ovarian cancer, so symptoms alone are not sufficient to refer to secondary care. An initial test using an objective and standardised assessment in symptomatic women reduces observer variability. Serum tumour markers fulfil these criteria. CA125 is currently the most widely used and reliable ovarian cancer tumour marker.
The clinical evidence demonstrated that no single test on its own adequately selected a manageable number of women for referral to secondary care. The combination of raised serum CA125 and sequential ultrasound of the abdomen and pelvis reduced significantly the number of women who would be referred, although a greater proportion of symptomatic women would be directed to the right pathway in a more timely fashion.
Additional information:
There is considerable variation in practice across the UK as to what tests are currently performed in primary care. In addition, many women are being referred to other specialists in error.
Recommendations in full: KPIs
Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer (see section 1.1.1) [ ]
• If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis. [ ]
• For any woman who has normal serum CA125 (less than 35 IU/ml), or CA125 of 35 IU/ml or greater but a normal ultrasound:
assess her carefully for other clinical causes of her symptoms and investigate if appropriate
if no other clinical cause is apparent, advise her to return to her GP if her symptoms become more frequent and/or persistent [ ]
Related recommendation:
If the ultrasound suggests ovarian cancer, refer the woman urgently1 for further investigation2 [ ]
1 An urgent referral means that the woman is referred to a gynaecological cancer service within the national target in England and Wales for referral for suspected cancer, which is currently 2 weeks.
2 See also ‘Referral guidelines for suspected cancer’ (NICE clinical guideline 27; available at for recommendations about the support and information needs of people with suspected cancer.
Suggestive of ovarian cancer
Yes No
Refer urgently
Investigate
Advise to return to GP if symptoms become more frequent and/or persistent 21

23. Detection in primary care
Women presents to GP
Ascites and/or pelvic or abdominal mass
GP assesses symptoms
Support and information
Tests in primary care
NOTES FOR PRESENTERS:
Key points to raise:
In this next section we will now discuss ‘awareness of symptoms and signs’ and the first tests outlined in the guideline.
For a more detailed algorithm on ‘detection in primary care’ see page 7 of the QRG.
A podcast explaining primary care tests and clinical case scenarios has been produced to support implementation of the guidance – see slide 27
Suspicion of ovarian cancer
Urgent referral: assessment in secondary care 23

24. Establishing the diagnosis
CT scan
Complex pelvic mass
Omental cake
Liver surface deposits

25. Establishing the diagnosis
Discuss in MDT
Suspected early stage disease → local cancer unit
Advanced disease → cancer centre

26. Treatment of Early Ovarian Cancer

27. Surgery Suspected early stage disease Staging Laparotomy
TAH / BSO
Infracolic omentectomy
Pelvic / PA node sampling
Peritoneal washings
Biopsies of peritoneum
Fertility sparing surgery
Laparoscopic surgery

28. Surgery

29. Staging Stage important in prognosis and treatment 5 year survival
60%
20%
5 year survival
Stage %
Stage %
Stage %
Stage %
1090 patients
Leeds Cancer Centre

30. Treatment of Advanced Disease
Surgery or
Primary Chemotherapy?

31. 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

32. Surgery for advanced disease
MDT review
Disease considered resectable
Medically fit
→ debulking surgery

33. 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?

34. “Inoperable disease”

35. Neoadjuvant Chemotherapy and Interval Debulking Surgery
Disease not resectable
Medically unfit
Scan guided core biopsy
3 cycles chemo → IDS → 3 cycles chemo

36. Neoadjuvant Chemotherapy and Interval Debulking Surgery
Future standard of care?
Reduced morbidity and mortality
Results of CHORUS awaited

37. Chemotherapy
Early stage disease

38. Early stage disease
Stage I & II
Died
Alive

39. Early stage disease Stage I & II
Adjuvant Chemotherapy - Increase chance of cure
Died
Cured by chemo
Alive
ICON1/Action: JNCI 2003

40. Early stage disease Current practice Likely benefit Uncertainty
Stage 1c or higher
Grade 3
Clear cell histology
Uncertainty
Peri-operative rupture (surgical 1c)
Inadequate staging
Chemotherapy vs repeat staging procedure

41. Chemotherapy
Advanced disease

42. Chemotherapy Stage III & IV disease Control cancer Prolong life
Improve symptoms
First line
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
Palliative

43. Epithelial Ovarian Cancer
First-line chemotherapy
Carboplatin & Paclitaxel
6 cycles weekly
18 weeks - weekly (low dose)
Carboplatin

44. Chemotherapy Side effects Fatigue Nausea & vomiting Myelosupression
Anaemia, risk of infection
Hair loss
Neuropathy
Mucositis
Skin & nail changes
Allergic reactions

45. Future Developments Prevention Screening for early disease Surgery
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

46. Future Developments Chemotherapy Improved systemic therapy
Increased dose intensity
Biological agents e.g. VEGF inhibitors
Improved therapy delivery
Intraperitoneal chemo

47. Future developments Intra-peritoneal chemotherapy
Suggestion of improved survival
Increase in side effects

48. Summary Poor prognosis due to late presentation Early disease curable
Advanced disease treatable but not curable

49. Summary Will NICE guidelines make any difference?
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!!

50. Thank You