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Ovarian cancer: Ensuring early diagnosis
www.tnpj.com The Nurse Practitioner • September XXXXXXXXXX
varian cancer is the most fatal of all gynecologic
cancers. There is a widespread misconception that
ovarian cancer is a “silent killer,” despite fi ndings
of common warning symptoms.1-6 Unfortunately, the symp-
toms that accompany ovarian cancer are typically subtle and
associated with other benign conditions (see Symptoms of
ovarian cancer).1,5,7,8 Patients and practitioners therefore
tend to overlook the vague symptoms or investigate other
potential conditions not associated with the ovaries, ulti-
mately leading to late diagnoses.5 In fact, more than 70%
of women will be diagnosed in Stage III or IV; less than
30% are diagnosed at Stage I.1-4,6,7 At Stages III and IV, a
woman’s chance of surviving 5 years is as low as 20% and
6%, respectively.7 Conversely, women with Stage I ovarian
cancer have a 90% chance of surviving 5 years.3,5-9 Diagno-
sis at an earlier stage would improve prognosis and greatly
increase a woman’s overall chance of survival.3,5 Effective
screening programs would help nurse practitioners (NPs)
By Christa L.P. Slatnik, NP, RN, BN and Elsie Duff, NP, BScN, MEd
O
Abstract: Ovarian cancer is the most fatal of all gynecologic malignancies. Despite the lack of
a recommended screening test for ovarian cancer, NPs can identify risk factors, ensure patients
are aware of subtle symptoms, and provide adequate testing and analysis of results.
Keywords: abdominal distension; CA 125; early diagnosis gynecologic malignancy; cancer survival;
BRCA1, BRCA2, and MMR mutations; ovarian cancer; pelvic pain; screening; subtle symptoms; ultrasound Ph
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ARIAN CANCEREnsuring
early diagnosis
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
48 The Nurse Practitioner • Vol. 40, No. 9 www.tnpj.com
Ovarian cancer: Ensuring early diagnosis
diagnose patients in the earliest stages of ovarian cancer.
Unfortunately, a screening test has yet to be established
for ovarian cancer. Recent studies have shown that ovarian
cancer may actually originate in a premalignant state with
lesions in the distal fallopian tube, which would make the
prospect of screening tests able to detect ovarian cancer
efore it develops promising.3
■ Why screening is not recommended
Over twenty-five years ago, the cancer antigen 125 (CA
125) was considered a promising tumor marker for ovar-
ian cancer, and it was initially anticipated that this marker
would allow for screening among the general public.3
With further use, however, the CA 125 test was found to
lack specificity, as this marker can be increased due to
ovarian cancer but also a variety of benign causes (en-
dometriosis, age, race, menstrual cycle, pregnancy, and
hysterectomy) as well as other malignancies (pancreas,
east, colon, and lung cancers).3 The CA 125 test has
also been found to lack sensitivity. For example, although
increased levels of this marker have been found in up to
90% of women affected by advanced stages of ovarian
cancer, values remain normal in up to 50% of patients in
earlier stages of cancer.2,7,8 Due to this lack of specificity
and sensitivity, using the CA 125 test as a screening tool
for ovarian cancer could lead to stressful false-positives
and misleading false-negatives. Therefore, a CA 125 test
is not recommended.
Transvaginal sonography (TVS) has shown promise
in screening for ovarian cancer, as it is highly sensitive to
pelvic masses.2 Unfortunately, due to its lack of specifi city,
it produces false-positive results that lead to unneces-
sary surgical procedures.2,3 If used as a screening tool, the
TVS test would require an estimated 5,200 ultrasounds
e performed to detect one case of invasive carcinoma.5
Despite the expectation that combining the TVS with the
CA 125 would increase the specifi city and help decipher
which pelvic masses were malignant, the predictive values
were shown to be less than expected (less than 5%) with
no notable decrease in mortality from ovarian cancer.3,10,11
Routine screening with the CA 125 and TVS tests com-
ined is therefore not recommended due to the increased
isk of harm from high rates of false-positive results.5,11
Studies have shown that the screening ability of up to
28 other biomarkers demonstrated no improvement over
the CA 125.3,10 However, the human epididymis protein 4
(HE4) is a newer serum biomarker that is showing prom-
ise as a potential screening tool when combined with the
CA 125 and TVS tests.2,3,8 The HE4 biomarker may aid in
screening, since it is more sensitive than other markers.
Thirty-two percent of women with ovarian cancer and a
negative CA 125 have a positive HE4.2 However, although
the HE4 biomarker is highly expressed by ovarian cancers,
it is a nonspecifi c test with elevations also occu
ing with
changes in the trachea and salivary gland.2 To date, limited
esearch has been conducted to determine the overall speci-
fi city and sensitivity of the HE4 biomarker, especially with
effect on mo
idity and mortality.2 The U.S. FDA has in
turn limited the HE4 biomarker to be used for monitoring
the recu
ence of ovarian cancer until further research is
completed.2
On the whole, more research is essential in order to
establish a highly-specifi c and sensitive screening test that
will detect ovarian cancer in the earliest of stages, prefer-
ably in a premalignant state. Until such a screening test is
identifi ed, NPs must pay special attention to those at risk
while ensuring all patients are aware of the vague signs and
symptoms to watch for and the importance of following up
in a timely manner if any arise.
■ Paying special attention to those at risk
Even though ovarian cancer can occur in a woman with no
established risk factors, identifying those at a higher risk of
developing the disease may help the NP ensure adequate
awareness and follow up, and in turn, early diagnosis.2,3,5
A family history of ovarian cancer is a risk factor with
5% to 20% of those affected by ovarian cancer having a
familial history of the disease.2,3,7 Genetic risk for ovarian
cancer has been primarily associated with mutations of the
Symptoms of ovarian cancer1,5,7,8
• Recent unexplained, increased abdominal size
• Abdominal distension
• Bloating
• Back or abdominal pain
• Pelvic pressure or pain
• Loss of appetite
• Feeling full quickly
• Diffi culty eating
• Changes in bowel habits (constipation or dia
hea)
• Urinary symptoms (frequency or urgency)
• Unexplained weight gain or loss
• Fatigue
• Postmenopausal bleeding
• Menstrual i
egularities
• Rectal bleeding
• Suspected new diagnosis of IBS (particularly
if >50 years old)
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
50 The Nurse Practitioner • Vol. 40, No. 9 www.tnpj.com
Ovarian cancer: Ensuring early diagnosis
BRCA1, BRCA2, and MMR genes, which increase the life-
time risk of developing ovarian cancer from 1.6% to 40%,
18%, and 10%, respectively.3 If a patient has more than
one fi rst-degree relative who was diagnosed with ovarian
or
east cancer, particularly if they were diagnosed before
the age of 50 years, the NP must consider the potential
for a BRCA genetic mutation. If a patient has multiple
fi rst-degree family members affected by ovarian,
east,
endometrial, and/or colon cancers, the NP must consider
an MMR mutation or Lynch syndrome.3
Women with certain ethnic backgrounds, such as
Ashkenazi Jewish, French Canadian, Dutch, and Icelandic
descent, may also be at increased risk of having a genetic
susceptibility to ovarian cancer.5,12 Although research ana-
lyzing annual screening with the CA 125 and TVS tests has
een unable to show any effect on mo
idity and mortal-
ity among those with a familial risk of ovarian cancer, the
National Institutes of Health Consensus Panel on Ovarian
Cancer cu
ently recommends routine screening with these
tests for those with an established familial or genetic risk.2,3,5
Researchers in the United Kingdom and United States are
cu
ently evaluating the effectiveness of a screening pro-
gram, which would test younger women with a familial
history of ovarian cancer every 3 to 4 months.3 Until more
frequent testing has been shown to be effective at decreasing
mo
idity and mortality, annual CA 125 and TVS tests on
those with a familial risk must be combined with adequate
assessment of symptoms throughout the year in order to
ensure early detection.
In spite of the fact that there is a clear genetic link in
many cases, approximately 80% to 90% of ovarian can-
cers are sporadic, occu
ing in women with no apparent
genetic history.2,3,5 Therefore, it is essential to identify
other risk factors (beyond genetics) that could also place
a woman at risk for developing ovarian cancer. Age is a
common risk factor, with women over the age of 50 years
eing most likely to develop ovarian cancer.3,7 Inte
upted
ovulation appears to be a protective factor, as women who
have ovulated for fewer years tend to have a lower risk of
developing ovarian cancer.3 Because oral contraceptive
use, pregnancy,
eastfeeding, late menarche, and early
menopause all decrease the overall amount of ovulation
in a woman’s lifetime, assessing for those who have not
had any of these protective factors may identify a woman
at higher risk of developing ovarian cancer.3 NPs should
also utilize the awareness of the protective factor of inter-
upted ovulation in order to encourage women to com-
mence oral contraceptive use and/or
eastfeeding when
appropriate. Although screening has yet to be established
for those with an elevated risk, a future population-based
screening program is likely to include a risk-stratifi cation
algorithm that details a woman’s risk of developing ovar-
ian cancer combined with the CA 125 and TVS tests.3,7 For
example, by combining TVS ovarian morphology with CA
125 levels and menopausal status, a “risk of malignancy
index” (RMI) can be established to help decrease rates
of false-positives and improve detection of ovarian ma-
lignancies.3 Pending further research, known risk factors
are a useful means for NPs to assess and identify at-risk
women who will need immediate follow-up should any
suspicious symptoms arise.
■ Acknowledgment of symptoms
to ensure early detection
Although a