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  • Ovarian Cancer CMG January 2010 Final Version


    Document Title

    Guidelines for the Screening, Investigation and Management of Ovarian Cancers

    Document Date

    January 2010 Version 4 - Final

    Document Purpose

    This guidance has been produced to support the diagnosis, treatment and management of ovarian cancer Treatment decisions for individual patients require the weighing of a multiplicity of factors, which cannot all be accounted for in a CMG. The CMG provides a description of the range of treatment options available for a clinical scenario. To maximise the benefit of multiprofessional working management strategies for the individual are best discussed with a multidisciplinary meeting (MDM)


    Dr Ian Harley, Consultant Gynaecologist Prof Glen McCluggage, Consultation Pathologist Dr Sarah McKenna, Consultant Oncologist Dr Joanne Millar, Consultant Oncologist Dr Geoff McCracken, Consultant Gynaecologist Ms Wendy Cunnigham, Clinical Trials Ms Maureen Clarke, Patient Representative Ms Elish McColgan, Clinical Nurse Specialist Ms Pippa McCabe, Physiotherapist

    Version Changes

    Changes made to version 3 by Dr Ian Harley, Dec 09 Appendix 2 score for Menopause changed from

    4 to 3 Ms Pippa McCabe changed lymphodema paragraph Dec 09

  • Ovarian Cancer CMG January 2010 Final Version

    INTRODUCTION Ovarian cancer is the primary cause of mortality among gynaecological

    malignancies. The lifetime risk of ovarian cancer by age 75 years, in women

    from developed countries, is approximately 1 in 70 (Risch H.A, 2001). The

    median age at diagnosis is 60 years. In Northern Ireland ovarian cancer

    accounts for 4% of all cancers registered and is the commonest

    gynaecological malignancy. There are approximately 168 cases diagnosed

    annually in Northern Ireland. The mean overall survival is 32 months. (Cancer

    registry Northern Ireland)

    Primary ovarian tumours are histologically classified into those that are

    epithelial (implying an origin from the surface / coelomic epithelium), those

    that are of sex cord -stromal type, and originating from sex cord mesenchymal

    elements), and those that are of germ cell type (originating from germ cells).

    The majority of primary tumours (85-90%) are epithelial in origin (Im D.D,

    2001). Less commonly ovarian tumours may be metastatic from other primary

    sites, including non-gynaecological tumours.

    Epithelial tumours are further classified into distinct histological/morphological

    sub-groups (mainly serous, endometrioid, cleat cell and mucinous) based on

    microscopic appearances. A simplified version of the WHO classification for

    ovarian tumours is illustrated in Appendix 1.

    The majority of ovarian tumours are sporadic. However, 12% are familial

    cancers, due to an underlying genetic defect. Mutations in the BRCA1 and

    BRCA2 genes account for the majority (75-90%) of familial epithelial ovarian

    cancers, followed by mutations in Mismatch Repair genes (5-12%). Women

    with a BRCA1 or BRCA2 gene mutation have a 40-60% and 20-40% lifetime

    risk of developing epithelial ovarian cancer by age 75 years respectively. Risk

    of borderline and non-epithelial tumours do not appear to be greater in BRCA

    1/2 carriers than the background risk within the population.

  • Ovarian Cancer CMG January 2010 Final Version

    Patients with ovarian cancer commonly present with vague symptoms and

    signs. Consequently, most patients (85%) present with advanced disease.

    Thus a minority will present with early stage disease. In women with

    macroscopic disease confined to the ovary 25% will have a normal Ca125.

    30% will have microscopic spread to the lymph nodes and 22% will be

    upstaged by a comprehensive surgical staging procedure.

    Surgery is the primary treatment of choice. The aim of surgery is to remove as

    much tumour as is possible, provide surgical staging and histological

    diagnosis. Residual disease after initial surgery remains one of the most

    important variables in the prognosis for women with epithelial ovarian

    carcinoma (EOC). Although there are no randomized studies, nor are there

    likely to be, the best evidence available has resulted in cytoreductive surgery

    being the primary treatment in EOC. The aim is to debulk the tumour to less

    than 1cm of residual disease remaining in any site of the abdomino-pelvic

    cavity. If achieved, this is termed optimal cytoreduction (debulking).

    A meta-analysis by Bristow et all (2002) of 81 cohorts of patients (totalling

    6,885 cases) of stage III or IV EOC identified a significant improvement in

    survival in women who had maximal cytoreductive surgery. Maximal

    cytoreductive surgery was defined according to the largest diameter of

    residual disease. 95% of studies used 1cm or 2cm as discriminating criteria.

    Cohorts with 75% maximal

    cytoreduction who had a mean weighted median survival of 33.9 months


  • Ovarian Cancer CMG January 2010 Final Version

    SCREENING FOR OVARIAN CANCER As stated above, in the general population the lifetime risk of developing

    ovarian cancer by the age of 75 years is 1.4% (1 in 70). In the absence of a

    mutation in BRCA 1/2 the relative risk for women with one affected first degree relative is 3.1 (95% CI 0.3-1.6), ie: the lifetime risk is increased to

    4.3%. When more than one relative is affected (first or second degree) the relative risk is increased to 11.7 (95% CI 5.3 25.9), ie: the lifetime risk is

    increased to 16.38%.(Stratton J F).

    Patients with a strong family history of malignancy (including ovary, breast,

    bowel, pancreatic and prostate) should be referred to medical genetics for a

    risk assessment.

    Only those patients testing positive for BRCA1/2, HNPCC or on recommendation of medical genetics should be referred to the familial ovarian cancer screening clinic for ovarian screening or prophylactic surgery. The UKTOCS trial of ovarian cancer screening in the general population does

    not currently provide enough evidence to support the screening of

    asymptomatic women in the general population (Menon U et al Lancet 2009).

    Screening asymptomatic low risk women may lead to a larger number of

    unnecessary surgical interventions. However, the mature data should be

    available in 2014, including the outcome for unscreened women.

    The evidence does support screening high risk women for Ovarian Cancer. Screening methods currently used include a combination of history,

    examination, ultrasound scan of pelvis and Ca125.

    Women considered at high risk of ovarian cancer should be counselled for prophylactic surgery. The minimal surgical intervention should be a laparoscopic (or open if unsuitable for minimum access surgery) bilateral salpingo-oophorectomy. There is currently no data to support hysterectomy in addition to a BSO for prophylaxis of malignancy in patients with BRCA1/2 mutation.

  • Ovarian Cancer CMG January 2010 Final Version

    HRT therapy after Prophylactic Surgery in BRCA 1/2 mutation carriers Approximately 3% of invasive breast cancers are attributed to BRCA1 and 2

    (Newman B 1998). Women who carry a mutation in the BRCA 1 gene have a

    60-80% lifetime risk of developing breast cancer. This risk can be reduced by

    50% with prophylactic oophorectomy before menopause (Eisen A 2005,

    Rebbeck T 2009). Because the reduction of risk is believed to be due to the

    withdrawal of ovarian hormones, there is concern about the administration of

    exogenous hormones in women with the BRCA 1 or BRCA 2 mutation, to

    alleviate climacteric symptoms.

    In case control studies, BRCA1 and BRCA 2 carriers, who have had

    prophylactic BSO and are prescribed HRT, do not appear to loose the risk

    reduction for breast cancer (Rebbeck T 2005, Eisen A 2008). In these studies

    there appeared to be no difference in HRT preparation (Oestrogen alone or

    combined oestrogen and progesterone).

    BRCA 1 and BRCA 2 carriers who undergo prophylactic BSO should be

    carefully counseled of the effects of surgical menopause before surgery is performed. Post operative use of HRT should be discussed, including alternative treatments to relieve menopausal symptoms and prevent

    osteoporosis. Patients may be offered referral to the HRT clinic.

  • Ovarian Cancer CMG January 2010 Final Version

    DIAGNOSIS Suspicion for ovarian cancer should be made by the GP, Medical / Surgical

    clinician or Gynaecologist on taking a good clinical history and full

    examination. Appropriate initial investigations should be carried out on all

    women with a suspected ovarian malignancy before referral to the Lead

    Clinician of the Gynae. Cancer Unit.

    Investigations should include:

    Ultrasound scanning,

    relevant tumour markers (Epithelial: Ca125, Ca19-9 and CEA Germ

    Cell: AFP, hCG and LDH Sex Cord Stromal: Inhibin ) [Germ cell

    tumour markers should always be considered in younger women. It

    may be useful in young people to perform a serum calcium since

    ovarian small cell carcinoma of hypercalcaemic type, a rare but

    aggressive form of ovarian malignancy in young women, is associated

    in most cases with a raised serum level]

    +/- CT / MRI scan.

    These initial investigations may be supplemented by cytology or histology

    where appropriate.