Gynaecological cancers

Ovarian cancer
Ovarian cancer is a common malignancy that usually presents with advanced intra-abdominal
disease. It is the sixth most common cancer in Australian women with a lifetime risk of 1 in 70 and
a median age of diagnosis of 60 years. It is most common in developed Western countries and less
common in developing or Asian countries. A strong family history of breast or ovarian cancer is the
most relevant risk factor for ovarian cancer, with 10- 15% of diagnosed patients having a mutation
in the BRCA gene that confers susceptibility. Other risk factors include nulliparity, early menarche
and late menopause. Protective factors include oral contraceptive use, pregnancy, lactation, tubal
ligation and prophylactic salpingo-oophorectomy in mutation carriers. The tumour marker CA125
and transvaginal ultrasound are not effective measures of screening for ovarian cancer and are not
currently recommended for use in asymptomatic women.

The symptoms of ovarian cancer are non-specific and include bloating, abdominal pain, early
satiety and urinary urgency or frequency. Such symptoms should then be investigated with further
imaging and measurement of CA125. Transvaginal US is the initial investigation of choice.
Suspicious ovarian pathology should not be biopsied percutaneously as this may cause tumour
seeding. Referral to a gynaecologic oncologist for further evaluation is recommended. In the event
that ovarian carcinoma is discovered, extensive surgical staging should be performed including a
total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritoneal washings,
lymph node assessment and careful examination of all peritoneal surfaces. If advanced disease is
evident, debulking resection of all macroscopic disease to a residual of less than 1 cm, and surgery
in a high volume specialised centre, is associated with improved survival. The extent of disease
determines the stage (see Table 1), which is the most important determinant of long-term outcome.

Table 1: Stages of ovarian cancer

About 90% of ovarian cancer consists of epithelial ovarian cancer (EOC). Within EOC there are
different histologic sub-types, with the most common being high-grade serous carcinoma and less
common types including endometroid, clear cell and mucinous histology. It is now thought that
high-grade serous EOC originates from the Fallopian tube rather than the ovary itself. Less common
histologies are malignant germ cell tumours of the ovary, carcinosarcomas and sex cord-stromal
tumours. Primary Fallopian tube carcinomas and primary peritoneal carcinomas behave and are
treated in a similar fashion to EOC. Australian guidelines recommend that all women diagnosed
with a high-grade serous, endometroid or clear cell EOC below the age of 70 are referred for
BRCA1 and 2 mutation testing.
The majority of patients present with Stage III disease. Adjuvant chemotherapy following surgery is
recommended for some Stage I and all Stage II, III and IV disease in fit women, as this improves
long-term survival. This usually consists of 6 cycles of treatment with intravenous single-agent
carboplatin or carboplatin plus paclitaxel. Evidence also exists that women with Stage III disease
who are debulked to minimal residual disease gain additional benefit from some of the
chemotherapy being given via an intra-peritoneal route. Patients with ovarian germ cell tumours
require different chemotherapy regimens and should be managed in specialised units.

Most patients with advanced disease will develop recurrence following this initial treatment. They
may undergo debulking surgery again but usually are treated with more chemotherapy with the aim
of improving symptoms and quality of life. The effectiveness of chemotherapy diminishes with
each administration as the tumour becomes progressively resistant, even if different drugs are used.
Troublesome symptoms of advanced disease including recurrent ascites, abdominal pain and small
bowel obstruction require skilful palliation.

Endometrial cancer
Endometrial cancer is the seventh most common malignancy, which will be diagnosed in 1 in 50
Australian women. Oestrogen without progesterone use is a potent risk factor, as is obesity due to
oestrone production by adipocytes. In Western countries, it is the most common female genital tract
malignancy with increasing incidence due to increasing obesity. Inheriting a mutation in one of the
Lynch syndrome genes is also a risk factor.

The presenting symptom in 90% of cases is post-menopausal bleeding, which permits diagnosis at
an early stage. This symptom should be investigated with endometrial sampling via bedside pipelle
or dilation and curettage performed under anaesthesia. The most common histological type of
endometrial cancer (Type I) is endometrioid adenocarcinoma, which originates from atypical
endometrial proliferation and is oestrogen driven. Less common Type II endometrial cancers are
more aggressive and include serous, clear cell and carcinosarcoma.

Surgery is frequently curative treatment and provides additional staging information. The most
relevant staging criterion indicating disease at higher risk of relapse is the presence of lymph node
involvement. High histologic nuclear grade also indicates a worse prognosis. For early disease
limited to the uterus, total abdominal hysterectomy and bilateral salpingo-oophorectomy is
sufficient, but more extensive surgical staging similar to EOC may be recommended for more
advanced disease. Lymph node sampling or dissection may be performed for disease with deep
uterine myometrial invasion or aggressive histology to give additional staging/prognostic
information but has not been shown to reduce mortality. Laparoscopic hysterectomy may be
associated with reduced post-surgical morbidity in appropriate cases.

Table 2: Stages of endometrial cancer

Those women diagnosed at a younger age or with a family history of other Lynch syndrome
associated cancers such as bowel cancer should be referred for consideration of genetic testing.
Initial screening for this involves assessment of the resected cancer for the presence of micro-
satellite instability.

Optimum adjuvant treatment of endometrial cancer is still evolving. Most recurrences of

endometrial cancer are local, occurring in the surgical field. Radiotherapy delivered via external
beam or by direct insertion of an applicator containing radioactive source into the vagina
(brachytherapy) reduces the chance of local recurrence but does not impact on overall survival. For
low risk early-stage disease (Type I, Stage I or II, low grade, without lymphovascular invasion) the
aim is to avoid over-treatment, and observation with or without vaginal brachytherapy is
appropriate. Such brachytherapy has less impact on quality of life than external beam treatment. For
higher stage or high risk disease, adjuvant chemotherapy may be used in addition to external beam
pelvic radiotherapy, particular for those with residual disease where the chance of developing
metastatic disease is high. The role of chemotherapy in earlier stage disease is being explored in
clinical trials. For locally recurrent disease, salvage radiotherapy or surgery may cure patients. For
disseminated recurrence, treatment options include progestogens particularly for Type I well-
differentiated disease, or chemotherapy for Type II or aggressive Type I disease.

Cervical cancer
Cervical cancer is the second most common cancer affecting women worldwide, particularly in
developing countries. It is caused by infection with the human papillomavirus (HPV), the most
common sexually transmitted infection in the world. Serotypes 16 and 18 of HPV are responsible
for 70% of cervical cancer. Persistent HPV infection leads to the development of cervical
intraepithelial neoplasia, a precancerous lesion, at the transformation zone of the cervix.
Immunosuppression as seen in HIV or post organ transplant is a risk factor for persistent infection
and cancer development. Smoking is an additional risk factor. The precancerous lesions may be
detected by cervical smear and observed closely following it’s ablation via conisation, cauterisation
or large loop excision of the transformation zone (LLETZ). Because of the effectiveness of
screening with Pap smears, cervical cancer is now rare in Australia, with only around 800 cases
diagnosed each year, mostly in those from disadvantaged backgrounds who have not participated in
screening. The recent development of HPV vaccines should eventually reduce the incidence of
cervical cancer by preventing the major risk factor.

Most cervical cancer is of squamous cell histology (80%), with adenocarcinoma being less
common. It presents with abnormal vaginal bleeding or vaginal discharge, and is also commonly
discovered via screening cervical smear which is recommended for all sexually active women.
Staging is based on clinical examination, but may be aided by the use of MRI and PET scans used
to delineate invasion into surrounding structures or nodal spread and for planning of appropriate
treatment. The International Federation of Gynaecology and Obstetrics (FIGO) staging system is
shown in Table 3.

Table 3: Stages of cervical cancer

For Stage I disease, surgery is an option, which may preserve ovarian function in younger patients.
Outcomes are equally good with external beam radiotherapy followed by brachytherapy, but this
will induce menopause. For more locally advanced disease, combination chemotherapy and
radiotherapy is the treatment of choice and is able to cure two thirds of women. Metastatic disease
is managed with chemotherapy along with optimum palliative care.