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Ovarian cancer – not
quite a ‘silent killer’
Ovarian cancer is often asymptomatic until the late stages, but there are
certain signs to look out for, write Peter Hayes and Siobhan Carruthers
Ovarian cancer is a serious disease. According to the
Irish Cancer Society, there are 300 or so new diagnosed
cases in Ireland per year and about 200 deaths. It often
presents when a cure is no longer possible. There are few
early warning signs; however, there are certain symptoms
that GPs should be aware of. We want to highlight some of
the few ‘warning shots’ that exist and follow on with a brief
up-to-date review of many of the management issues.
Main risk factors1-4
• Repeated ovulations (long menstrual lifetime, null parity,
not breastfeeding, infertility)
• G enetics (BRCA gene/breast-ovary syndrome, Lynch
syndrome/colon-ovary syndrome, strong family history of
ovarian cancer)
• P ostmenopausal oestrogen (hormone replacement
treatment)
• Cigarettes and increased body mass index
• E ndometriosis (2.5% lifetime risk of ovarian
malignancy).6
Symptom watch for ovarian cancer7,9,10-12
• Abdominal/pelvic pain
• Abdominal swell/bloating
• Feeling unusually full post meals
• Urinary urgency.
If any of these symptoms are present in women, especially in those over 50 years, then the symptom index is
positive. These symptoms, if present for less than one year
and are present more than 12 times per month, give a
sensitivity of 56% for early disease and 79.5% for late
disease. The specificity is 86.7%-90%.14
If you combine the symptom index being positive with
either a raised CA-125 or the new ovarian tumour marker
HE-4, then the sensitivity becomes 84% and the specificity 98%.14 A new onset of irritable bowel disease-type
symptoms in a woman over 50 years should also ring
an alarm bell about ovarian cancer issues. Colonoscopy
referral, while important, should maybe occur parallel to
gynaecological referral.
Signs5
The signs of ovarian cancer are notoriously silent until the
late stages of the disease when a patient will often have:
pelvic mass on exam and/or ascites/pelvic lymph nodes.
Table 1
Detection of ovarian cancer in primary care*
Woman presents to GP
Physical examination
identifies ascites and/or
a pelvic or abdominal mass
(not obviously uterine fibroids)
Woman reports having any of the following symptoms
persistently or frequently – particularly more than 12
times per month (especially if she is 50 years or over)5
• Persistent abdominal distension (’bloating’)
• Feeling full (early satiety)
and/or loss of appetite
• Pelvic or abdominal pain
• Increased urinary urgency and/or frequency
OR:
Woman is 50 years or over and has had symptoms
within the last 12 months that suggest IBS6
Woman reports any of
the following symptoms:
• Unexplained weight loss
• Fatigue
• Changes in bowel habit
Symptoms not
suggestive of
ovarian cancer
Ovarian cancer
suspected?
Yes
No
Measure serum CA125
≥ 35 IU/ml
Arrange ultrasound of
abdomen and pelvis
Suggestive of
ovarian cancer
Refer urgently
*Adapted from NICE 2011 www.nice.org.uk/cg122
< 35 IU/ml
Normal
Assess carefully: are other clinical
causes of symptoms apparent?
Yes
Investigate
No
Advise her to return if
symptoms become more
frequent and/or persistent
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Treatment staging and survival rates15
Stage
Treatment
Outcome/five-year survival
Stage 1a/1b
Surgery removing the uterus, fallopian tubes and one or both ovaries.
Conservative surgery spares the uterus and one ovary
90% survival
Stage 1c/2
Surgery as above but with adjuvant chemotherapy
50% relapse within five years
Stage 3/4
Pelvic de-bulking operations and adjuvant chemotherapy but with
eventual palliation. Treatment is decided on a person-by-person basis
Five-year survival low, 75% of cancers
diagnosed here
Diagnosis
All cases with suspicious symptoms or signs should be
referred from primary to secondary care for assessment.
This will involve examination and imaging with ultrasound
if not already performed. A CA-125 tumour marker should
also be performed.
Care pathway (adapted from NICE 2011)
If a patient presents with the following symptoms they
may be managed initially in primary care according to the
skill level of the practitioner:
• Positive symptom index (listed previously)
• New irritable bowel type symptoms aged over 50 years
• Anxiety about risk factors.
GP with little experience in gynaecology: Refer all of the
above groups to secondary care for opinion.
GP with some training in gynaecology: Perform a CA-125
serum test and refer if higher than accepted limits. If the
CA-125 is within normal limits, a careful re-evaluation
of symptoms and re-assessment examination should take
place. Further investigations to other organ systems can be
organised if appropriate.
GP with specialist interest in gynaecology: If CA-125 is
elevated you may wish to order an ultrasound of pelvis.
If the ultrasound does not show any suspicious signs of
malignancy then a careful follow-up and monitoring process may take place. This should occur along with a careful
re-evaluation of symptoms and re-examination to rule out
the involvement of other organ systems.
The patient with ‘clinical signs’ on exam such as ascites
or pelvic lymph nodes should be referred to secondary care
expediently in all cases.
Screening without symptoms in the general population
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer
Screening Trial of the National Cancer Institute (2011)16
has recently published its findings. It performed yearly
CA-125 blood tests on women for six years and annual
ultrasound tests for four years. The effect of screening on
this group’s mortality was dubious. Screening was felt to
be unbeneficial. It was felt that screening probably causes
harm, with far too many false positive patients being identified and operated on.
The UKTOCS trial is ongoing and will have results in late
2014. This trial compares three screening possibilities: a
no screening arm; an annual ultrasound screening arm; and
a combined CA125 and ultrasound (if CA-125 raised) arm.
The results are eagerly awaited.
Many combined tumour marker groups have been used in
studies of general population screening for ovarian cancer.
These combine CA-125 with other tumour markers in an
attempt to increase specificity and sensitivity in these
blood markers diagnosing ovarian cancer. None are proven,
but the latest ongoing studies are using a panel profile of
circa 30 blood tumour markers.13
Staging
Staging details are usually not of relevance to primary
care providers but with patients who are diagnosed with
ovarian cancer surviving longer than ever before, it is plausible that these types of patients may need a ‘chronic-care’
type model of care (see Table 2).
Follow up for successful treatment of stage 1 and stage 215
Follow up every three months for two years, then every six
months for a further three years and annually thereafter.
Research/other treatment options
Neo-adjuvant chemotherapy is also used in some centres
for late stage disease where the chemotherapy happens
before the de-bulking surgery.
Radiotherapy is not an option for most patients as the
problems with pelvic irradiation outweigh the benefits
Intra-peritoneal chemotherapy is currently in trials. The
port is a trans-abdominal opening and placed at laparotomy/laparoscopy.
Peter Hayes is in practice in Limerick city and teaches at NUI
Galway and Siobhan Carruthers is a tutor in obstetrics and
gynaecology at NUI Galway
References
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2002; 155217
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