Editorial
Ovarian Cancer Is Not So Silent
Barbara A. Goff, MD
See related article on page 157.
Barbara A. Goff is from the Department of Obstetrics
and Gynecology at the University of Washington,
Seattle, Washington; email: bgoff@uw.edu.
Financial Disclosure
The author did not report any potential conflicts of
interest.
© 2022 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer
Health, Inc. All rights reserved.
ISSN: 0029-7844/22
VOL. 139, NO. 2, FEBRUARY 2022
© 2022 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
F or more than 30 years, investigators have attempted to develop screen-
ing strategies for early detection of ovarian cancer. Given that survival
rates for stage I and II disease are 70–90%, compared with 10–30% for
stage III and IV, and that 60–70% of ovarian cancers are diagnosed in late
stages, any strategy that allowed for diagnosis in early stages would likely
show a survival benefit.1 Large prospective randomized trials, such as the
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
and the UK Collaborative Trial of Ovarian Cancer (UKCTOCS), have
evaluated combinations of transvaginal ultrasonography and tumor
markers as a screening strategy.2 Unfortunately, despite enrolling almost
300,000 women, screening with these modalities has not resulted in a
reduction in mortality for screen-detected ovarian cancers compared with
routine care. Although there are novel approaches to identifying tumor
DNA in blood, Pap tests, and urine, currently no screening test is recom-
mended for women with average risk. The U.S. Preventative Services
Task Force has consistently given ovarian cancer screening a grade D
recommendation, which means screening for ovarian cancers should be
excluded from a periodic health examination because more women are
harmed from screening (unnecessary surgery) than helped. So, in 2022,
we continue to make the diagnosis of ovarian cancer predominantly
through symptom recognition and diagnostic testing based on patient
history and physical examination. Accordingly, the American College
of Obstetricians and Gynecologists states in their Committee Opinion
on the role of the obstetrician–gynecologist in the early detection of
ovarian cancer that, “Educating women and practitioners about
symptoms and promptly initiating follow-ups is currently the best
method of diagnosis.”3
Nonetheless, for years, ovarian cancer has been described inaccurately as
a silent killer, or that symptoms are too vague for patients or health care
professionals to recognize. Another myth is that only women with advanced-
stage disease have symptoms before diagnosis. In this month’s issue of Obstet-
rics & Gynecology, Chan and colleagues4 add to a large body of literature
demonstrating that women with ovarian cancer do have symptoms, including
most of those with stage I and II disease. Through retrospective chart review
of women enrolled in a Gynecologic Oncology Group study to evaluate the
efficacy of three compared with six cycles of paclitaxel and carboplatin as
adjuvant therapy, investigators found that, of 419 women with early-stage
ovarian cancer, 301 (72%) had documentation of symptoms typical of ovar-
ian cancer—most commonly abdominal or pelvic pain, bloating, and
increased abdominal size. Gastrointestinal symptoms were not as common
as reported in other studies.5 In addition, there was no difference in symptom
presentation based on stage or histology. Women with large tumors were
more likely to have multiple symptoms recorded in the medical record. In
surveys that ask women directly about symptoms, 89% of those with early-
stage ovarian cancer report having symptoms before diagnosis.5,6 Correlation
of symptoms documented by health care professionals with patient-reported
OBSTETRICS & GYNECOLOGY 155
symptoms has not been evaluated for women with ovar-
ian cancer; nonetheless, it is not unexpected that Chan
et al’s reported percentages of symptomatic women are
slightly lower than what have been found with direct
patient surveys.
Many health care professionals are seemingly
unaware of the symptoms typically associated with
ovarian cancer, so misdiagnosis remains common. In
a survey of 1,725 women with ovarian cancer,5 70%
had symptoms for more than 3 months before their
diagnosis. The most common symptoms were bloat-
ing, increased abdominal size, abdominal and pelvic
pain, urinary symptoms, and changes in bowel habits.
When patients with ovarian cancer were asked what
their doctors told them was wrong when they reported
symptoms, 15% were told they had irritable bowel
disease, 13% were told nothing was wrong, 12% were
diagnosed with stress, 9% with gastritis, 6% with con-
stipation, and 6% with depression. Prescription med-
ication for a condition other than ovarian cancer was
given to 30% of patients with ovarian cancer. Clearly,
health care professionals struggle with understanding
what symptoms are concerning for ovarian cancer.
One of the concerns about the symptoms of ovarian
cancer is that they can be vague and commonly present
in the general population. In a case–control study of
more than 1,600 women presenting to a primary care
clinic compared with women with early-stage ovarian
cancer,7 the odds ratios for symptoms were 2.2 for
abdominal or pelvic pain, 2.4 for urinary urgency, 2.5
for difficulty eating, 3.6 for bloating, and 7.4 for
increased abdominal size. However, the more significant
findings were that women with ovarian cancer typically
had symptoms that were of more recent onset and expe-
rienced their symptoms almost daily, compared with
over a year-long history of episodic symptoms occurring
two to three times a month for the clinic population.
Chan et al were not able to assess for frequency or
duration of symptoms, which may be an important fac-
tor in distinguishing symptoms that are more concerning
for ovarian cancer. Other researchers have developed
an ovarian cancer symptom index, which includes hav-
ing one of six symptoms (abdominal or pelvic pain,
increased abdominal size or bloating, and difficulty eat-
ing or feeling full quickly), with these symptoms occur-
ring more than 12 times a month and being present for
less than a year as being moderately sensitive (67–87%),
with specificity of 80–90% in women with ovarian can-
cer.8 Symptom-triggered screening has been used suc-
cessfully in prospective studies.9 In the DOvE trial
(Diagnosing Ovarian Cancer Early), investigators found
that assessment of ovarian cancer symptoms followed by
diagnostic testing with pelvic ultrasonography and CA
156 Goff Ovarian Cancer Is Not So Silent
© 2022 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
125 led to a high detection rate and a trend toward
earlier diagnosis and better outcomes.10 Importantly,
the incidence of ovarian cancer in the symptomatic pop-
ulation was more than 10 times greater than in the gen-
eral public.
The study by Chan et al adds more information that
a large majority of women with ovarian cancer, even
those with early-stage disease, have symptoms. Both
patients and health care professionals should be educated
about these symptoms, and we all need a high index of
suspicion in symptomatic patients to avoid delays in
diagnosis. Women with early-stage disease have survival
rates that are more than double those in women with
advanced-stage disease; therefore, symptom recognition
with appropriate diagnostic testing remains very impor-
tant in our efforts to improve outcomes.
REFERENCES
1. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L,
Isaacs C, et al. Effect of screening on ovarian cancer mortal-
ity: the Prostate, Lung, Colorectal and Ovarian (PLCO)
Cancer Screening Randomized Controlled Trial. JAMA
2011;305:2295–303. doi: 10.1001/jama.2011.766
2. Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A,
Karpinskyj C, et al. Ovarian cancer population screening and
mortality after long-term follow-up in the UK Collaborative
Trial of Ovarian Cancer Screening (UKCTOCS): a randomised
controlled trial. Lancet 2021;397:2182–93. doi: 10.1016/S0140-
6736(21)00731-5
3. The role of the obstetrician–gynecologist in the early detection
of epithelial ovarian cancer in women at average risk. Com-
mittee Opinion No 716. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2017;130:e146–9. doi: 10.
1097/AOG.0000000000002299
4. Chan JK, Tian J, Kesterson JP, Monk BJ, Kapp DS, Davidson B,
et al. Symptoms of women with high-risk, early-stage ovarian
cancer. Obstet Gynecol 2022;139:157–62. doi: 10.1097/AOG.
0000000000004642
5. Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian car-
cinoma diagnosis. Cancer 2000;89:2068–75. doi: 10.
1002/1097-0142(20001115)89:10,2068::aid-cncr6.3.0.co;2-z
6. Olson S, Mignone L, Nakraseive C, Caputo TA, Barakat RR,
Harlap S. Symptoms of ovarian cancer. Obstet Gynecol 2001;
98:212–7. doi: 10.1016/s0029-7844(01)01457-0
7. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency of
symptoms of ovarian cancer in women presenting to primary care
clinics. JAMA 2004;291:2705–12. doi: 10.1001/jama.291.22.2705
8. Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schur-
man KM, et al. Development of an ovarian cancer symptom
index: possibilities for earlier detection. Cancer 2007;109:221–
7. doi: 10.1002/cncr.22371
9. Andersen MR, Lowe KA, Goff BA. Value of symptom-
triggered diagnostic evaluation for ovarian cancer. Obstet Gy-
necol 2014;123:73–9. doi: 10.1097/AOG.0000000000000051
10. Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, et al
Assessment of symptomatic women for early diagnosis of ovar-
ian cancer: results from the prospective DOvE pilot project.
Lancet Oncol 2012;13:285–91. doi: 10.1016/S1470-2045(11)
70333-3
OBSTETRICS & GYNECOLOGY