Original Research ajog.

org

GYNECOLOGY
Ultrasound characteristics of early-stage high-grade
serous ovarian cancer
Elizabeth Suh-Burgmann, MD; Natasha Brasic, MD; Priyanka Jha, MBBS; Yun-Yi Hung, PhD; Ruth B. Goldstein, MD

BACKGROUND: Survival from ovarian cancer is strongly dependent on
the stage at diagnosis. Therefore, when confronted with a woman with an
isolated adnexal mass, clinicians worry about missing the opportunity to
detect cancer at an early stage. High-grade serous ovarian cancers ac-
count for 80% of ovarian cancer deaths, largely because of their tendency
to be diagnosed at a late stage. Among adnexal masses, large size and the
presence of solid areas on ultrasound examination have been found to be
associated with cancer, but it is unclear whether these characteristics
identify early-stage cases.
OBJECTIVE: This study aimed to evaluate the ultrasound findings
associated with clinically detected early-stage high-grade serous ovarian
cancer.
STUDY DESIGN: This was a retrospective cohort study of women
diagnosed with stage I or II high-grade serous ovarian or fallopian tube
cancer measuring at least 1 cm at pathology from 2007 to 2017. Pre-
operative ultrasound examinations were independently reviewed by 3
radiologists. Adnexal masses were scored for size and volume; overall
appearance; presence, thickness, and vascularity of septations;
morphology and vascularity of other solid components; and degree of
ascites. Characteristics were compared between masses of <5 cm and
larger masses and between stage I and stage II cases. Interobserver
variability was assessed.
RESULTS: Among 111 women identified, 4 had bilateral ovarian
involvement, for a total of 115 adnexal masses characterized by
ultrasound examination. The mean age at diagnosis was 61.8 years
(range, 42e91 years). The median mass size was 9.6 cm (range,
2.2e23.6 cm) with 87% of cases having a mass size of
5 cm. A
mixed cystic and solid appearance was most common (77.4%), but a
completely solid appearance was more frequently seen for tumors of
<5 cm compared with larger tumors (26.7% vs 13.0%). Solid
components other than septations were seen in 97.4% of cases. The
characteristics of stage I and II cases were similar other than ascites,
which was more commonly seen in stage II cases (18.0% vs 3.1%,
respectively). Interobserver concordance was high for size and vol-
ume measurements (correlation coefficients, 0.96e0.99), with
moderate agreement observed across the other ultrasound charac-
teristics (Fleiss kappa, 0.45e0.58).
CONCLUSION: In this community-based cohort, early-stage high-
grade serous cancers rarely presented as masses of <5 cm or masses
without solid components other than septations. Our findings provide
additional support for the observation of small masses without solid areas
on ultrasound examination.
Key words: cancer, cyst, early detection, ovary, ultrasound

Introduction
Ovarian cancer is the most lethal of gy-
necologic cancers, responsible for
approximately 22,000 deaths annually.1
Stage is strongly associated with prog-
nosis, with
90% survival for women
with stage I cancer compared with 15%
to 20% survival for women with stage III
or IV cancer.2 Of the various types of
ovarian cancer, high-grade serous can-
cers account for approximately 80% of
deaths, largely because of their tendency
to be detected at a late stage.3 The failure
to detect high-grade serous cancers at the
early stage is a major reason why
Cite this article as: Suh-Burgmann E, Brasic N, Jha P,
et al. Ultrasound characteristics of early-stage high-grade
serous ovarian cancer. Am J Obstet Gynecol
2021;XX:x.exex.ex.
0002-9378/$36.00
ª 2021 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2021.04.262
screening has not resulted in improve-
ment in ovarian cancer mortality.4,5
Therefore, when confronted by a
woman with an adnexal mass, clinicians
often worry about missing the oppor-
tunity to detect cancer at an early stage.
The ultrasound characteristics of large
mass size and the presence of solid areas
on ultrasound examination have been
shown in several studies to be strongly
associated with malignancy.6e12 How-
ever, it is unclear to what degree these
ultrasound characteristics help identify
early-stage cancers, as most cancers
identified in studies, particularly high-
grade serous cancers, were late stage. As
early stage cases are relatively rare, no
studies have specifically evaluated the
ultrasound characteristics of early-stage
ovarian high-grade serous cancers,
despite the importance of their recog-
nition. The resulting uncertainty
regarding the ultrasound appearance of
early-stage cancers contributes to
concern for cancer even when worri-
some characteristics are absent.
Therefore, we analyzed the ultrasound
characteristics of early-stage high-grade
serous cancers among women diagnosed
over a 10-year period in a large
community-based setting.
Methods
This was a retrospective cohort study of
women diagnosed with stage I or II high-
grade serous ovarian cancer from 2007
to 2017. Participants were members of
Kaiser Permanente Northern California
(KPNC), a closed, integrated healthcare
delivery system, including 21 hospitals
that provide care for more than 4.2
million members whose racial and
ethnic diversity mirrors that of the
communities served. The study period
was selected as the period for which
complete tumor registry and electronic
medical record data were available.
Approval for the study was obtained

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Original Research GYNECOLOGY ajog.org

review; and women with tumors

AJOG at a Glance measuring <1 cm at pathology,
Why was this study conducted? including serous tubal carcinoma in situ
Although high-grade serous cancers account for 80% of ovarian cancer deaths, no and cases that were associated with a
study has evaluated the ultrasound characteristics of these cancers at an early concurrent benign adnexal neoplasm.
stage. Using electronic databases linked to the
medical record, all pelvic ultrasound
Key findings examinations performed within 1 year
Over 87% of early-stage high-grade cancers presented with an adnexal mass of >5 before cancer diagnosis were identified.
cm, with a median size of 9.6 cm. In 97% of cases, the mass demonstrated solid If women had more than 1 ultrasound
components other than septations. during this period, the first study was
used for analysis to characterize the mass
What does this add to what is known? at the earliest point of detection.
Our findings have indicated that although small adnexal masses are commonly The indication for ultrasound exami-
detected by ultrasound examination, they are an uncommon presentation of nation was determined by manual re-
early-stage high-grade serous ovarian cancer. The findings provide additional view of the “Indication” section of the
support for the observation of small masses without solid components. ultrasound report. In cases where the
stated indication was to follow up a
finding from another imaging study,
from the KPNC Institutional Review cancer) were identified from the in- such as computed tomography (CT), the
Board with waivers of informed consent stitution’s cancer registry, with manual “Indication” section for the other imag-
because of the retrospective nature of the medical record review to confirm diag- ing study was also reviewed to determine
study. nosis, stage, and histology. We excluded if it was potentially related to the mass.
Women with stage I or II high-grade women who did not undergo surgical For example, if the indication for ultra-
serous ovarian or fallopian tube cancer staging; women with borderline, low- sound examination was to follow up a
(henceforth referred together as ovarian grade, or nonserous histology on CT finding and the CT was done for
abdominal pain, the indication for the
FIGURE 1 ultrasound examination was considered
Flowchart to be pain, whereas if the CT was done
for a problem with no potential rela-
Women with stage I-II ovarian or fallopian tionship to the mass, such as surveillance
tube cancer diagnosed 2007-2017 with for abdominal aneurysm, the indication
serous histology was considered to be an incidental
we
N=257 women finding.
Ultrasound imaging files were dei-
dentified of all protected health infor-
Had pelvic ultrasound within 1 year prior to mation and independently reviewed by 3
Excluded: N=84, no ultrasound done within
diagnosis
1 year of diagnosis
radiologists (N.B., P.J., and R.B.G.), all of
N=173 women whom specialize in ultrasound and
women’s imaging. Each radiologist
independently assessed each ultrasound
Excluded: N=39 (not mutually exclusive)
imaging for technical adequacy to eval-
Low grade or other histology N=20 uate the adnexa, based on the quality of
Review of pathology confirmed stage I-II,
high-grade with
Staging not done or incomplete N=2 the available images. Studies deemed
Figure 2 displays the> mass
1 cm tumor
g at pathology
Not stage I-II N=6
inadequate for scoring because of tech-
N=134 women Tumor < 1 cm N=11
Concurrent benign neoplasm N=1 nical factors by at least 2 radiologists
were subsequently excluded from the
analysis.
Adnexal masses were characterized in
Ultrasound review by 3 radiologists
terms of (1) largest size dimension (in
Excluded: N=23, inadequate study quality
millimeters); (2) size dimensions in 3
N=111 women with 115 masses (4 cases
with bilateral cancer)
planes (in millimeters); (3) overall
appearance (mixed cystic and solid,
Flowchart of the study cohort. solid, multilocular, nonsimple unilocu-
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.
lar, or simple unilocular); (4) septations
(none, single or multiple, thick [
3

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ajog.org GYNECOLOGY Original Research

mm] or thin); (5) vascularity of septa-

TABLE 1
tions (NA [not applicable], no, yes); (6)
Patient characteristics
presence of other solid components (yes
or no); (7) morphology of solid areas Characteristic Value
(NA, smooth, entire mass is solid, Age at ultrasound (y)
irregular or papillary); (8) vascular flow
MeanSD 62.0 (11.5)
in solid component (NA, no, yes); and
(9) ascites (none or mild, moderate or Median (IQR) 61 (53e68)
severe). Normal postmenopausal ovaries Range, n (%) 42e91
were differentiated from small solid 18e39 0 (0)
masses based on irregularities of shape
40e49 14 (12.6)
or margins and presence of abnormal
internal flow. Septations were defined as 50e59 40 (36.0)
structures within cystic masses that tra- 60e69 31 (27.9)
verse from 1 wall to another and
70 26 (23.4)
considered thin if <3 mm in the greatest
width. If >1 cm bilateral ovarian tumor Race, n (%)
involvement was demonstrated on sur- White 68 (61.3)
gical pathology, both adnexa were scored Black 9 (8.1)
separately and treated as independent Hispanic 13 (11.7)
cases. Mass size was calculated as the
Asian or Pacific Islander 18 (16.2)
mean of the largest dimension as recor-
ded by 3 individual measurements. For Other 3 (2.7)
categorical features, agreement of at least Days from ultrasound to diagnosis
2 of the 3 radiologists was needed. If all 3 Median (IQR) 20 (10e36)
radiologists disagreed on how a feature
should be categorized, the study was re- Range 0e165
reviewed by all radiologists to arrive at a Primary location, n (%)
consensus. Ovary 98 (88.3)
The sonographic characteristics of
Fallopian tube 13 (11.7)
masses were compared for stage I vs II
cancer and for smaller vs larger masses. Stage, n (%)
We selected 5 cm as the size cutoff for I 63 (56.8)
comparison based on the view that II 48 (43.2)
masses of <5 cm are generally regarded as
BRCAþ or other deleterious mutation, n (%) 23 (20.7)
“small” from a clinical perspective. For
IQR, interquartile range; SD, standard deviation.
descriptive statistics, chi-square or the
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.
Fisher exact tests were used for categorical
variables, and unpaired t test was used for
continuous variables. Significance was identified. The inclusion and exclusion woman had surgery for large fibroids. Of
considered met at P<.05. Interobserver criteria are detailed in Figure 1. Among the 111 women included, 4 had bilateral
variability was assessed on the basis of those excluded were 11 women with adnexal cancer involvement for a total of
scores before re-review of discordant tubal carcinomas measuring <1 cm 115 abnormal adnexa scored. The most
scores. Correlation coefficients were (mean, 3.3 mm; range, 1e6 mm). In 7 of common indication for ultrasound ex-
determined for continuous variables, these cases, the occult tubal carcinoma amination was pain (33.3%), followed
such as mass size. For categorical vari- was found at the time of risk-reducing by mass on examination (23.4%), post-
ables, such as presence of ascites, the surgery for women known to be at menopausal bleeding (12.6%), and
Fleiss kappa was assessed. All statistical elevated risk because of a germline incidental finding on other imaging tests
analyses were performed using the Sta- BRCA mutation, with preoperative ul- (11.7%).
tistical Analysis System software (version trasound examination read as normal in The mean age at the time of surgery
9.4; SAS Institute Inc, Cary, NC). each case. For the remaining 4 women, was 61.8 years (median, 61 years; range,
occult tubal cancer was found inciden- 42e91 years). In all cases, the diagnosis
Results tally at the time of surgery that was of cancer was made on surgical pa-
After exclusions were applied, 111 performed for an unrelated abnormal thology, with a median time from index
women diagnosed with stage I or II high- ultrasound finding: 3 women had con- ultrasound examination to surgery of
grade serous cancer at surgery were current large benign ovarian cysts and 1 20 days (range, 0e165 days). Slightly

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Original Research GYNECOLOGY
FIGURE 2
Size distribution of masses
Associated with early-stage high-grade serous carcinoma
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.
more women were diagnosed with stage
I cancer (56.5%) vs stage II cancer. At
the time of data analysis, 23 women
(20.7%) had been found to carry a
BRCA or other deleterious germline
mutation (Table 1). Among these
women, the average age at ultrasound
examination was slightly younger at 59
years.
The median size of the associated
adnexal mass on ultrasound examina-
tion was 9.6 cm (range, 2.2e23.6 cm;
interquartile range, 6.8e13.6 cm), with
87% of tumors being at least 5 cm in size
(Figure 2). Overall, a “mixed cystic and
solid” appearance was most common
(77.4%), followed by “solid” appearance
(14.8%). However, among tumors of <5
cm, 53.3% were “mixed cystic and solid”
in appearance, with 26.7% having a
“solid” appearance compared with
11.7% of larger tumors. There was no
case associated with a simple unilocular
cyst. The presence of solid components
other than septations was the most
consistent characteristic for both smaller
and larger tumors, seen in 97.4% of cases
overall and demonstrating vascularity in
74.8% of cases (Table 2). Ascites was the
only characteristic that differed by stage
with moderate-to-severe ascites seen in
18% of stage II and 3.1% of stage I cases
(Table 3). Representative images are
showing in Figure 3.
1.e4 American Journal of Obstetrics & Gynecology MONTH 2021
Interobserver concordance for size
measurements was high with correlation
coefficients across the 3 radiologists of
0.98 to 0.99 for the largest size dimen-
sion of the mass and 0.96 to 0.98 for
volume as calculated by measurements
in 3 planes. For categorical features, the
Fleiss kappa ranged from 0.45 to 0.58,
indicating moderate agreement among
the 3 radiologists across the other
characteristics.
Comment
Principal findings
In this community-based cohort, we
found that early-stage high-grade serous
cancers rarely present as masses of <5
cm or as masses without solid areas other
than septations on ultrasound
examination.
Results
The finding that the median mass size in
these early-stage cases was 9.6 cm was
somewhat surprising given that high-
grade serous cancers are thought to be
often detected at advanced stages
because of their tendency to metastasize
early, before the primary tumor grows
large enough to produce symptoms.13,14
However, this finding is consistent with
data from the Prostate Lung Colorectal
Ovarian cancer screening trial, which
found that masses of <5 cm were rarely
ajog.org
malignant.15 An association between
solid components on ultrasound exam-
ination and risk of malignancy was
observed in the ultrasound screening
arm of the UK Collaborative Trial of
Ovarian Cancer Screening, which found
that masses without solid elements had
an absolute risk of 0.4% compared with
masses with solid elements that had an
absolute risk of 4.45%.11 In addition, our
results are generally consistent with the
ultrasound characteristics defined by the
International Ovarian Tumor Analysis
group’s 5 “Simple Rules” for identifying
ovarian malignancy: (1) irregular solid
tumor, (2) ascites, (3) at least 4 papillary
structures, (4) irregular multilocular-
solid tumor with the largest diameter
of at least 10 cm, and (5) very high color
content on color Doppler examination.8
Although the presence of solid compo-
nents on ultrasound examination has
been found in screening trials and other
studies to be associated with cancer,6e12
most high-grade serous cancers in those
studies were late stage. Our study sug-
gests that this association holds even for
early-stage cancers.
Clinical implications
Our findings indicate that although
small adnexal masses are commonly
detected by ultrasound examination,
they are an uncommon presentation of
early-stage high-grade serous ovarian
cancer. We previously reported that
among 1363 women over the age of 50
years with clinically detected complex
adnexal masses of <6 cm, the inci-
dence of cancer was 0.5%, and all
cancers that were initially observed
demonstrated growth on the first
follow-up ultrasound examination
with no apparent negative impact on
stage at diagnosis.16 Given that surgical
morbidity tends to be higher for older
women, ultrasound observation may
be appropriate when balancing poten-
tial benefits vs risks of surgical inter-
vention. The fact that nearly all
early-stage cancers demonstrated solid
areas other than septations on initial
ultrasound examination provides
additional reassurance and support for
observation of small masses without
solid components.
ajog.org GYNECOLOGY Original Research

TABLE 2
Ultrasound characteristics of adnexal masses associated with early-stage serous cancer by size
Variables Total (N¼115) Mass <5.0 cm (n¼15) Mass
5.0 cm (n¼100) P value
Appearance .019
Mixed cystic and solid 89 (77.4) 8 (53.3) 81 (81.0)
Multilocular 6 (5.2) 3 (20.0) 3 (3.0)
Solid 17 (14.8) 4 (26.7) 13 (13.0)
Nonsimple unilocular 3 (2.6) 0 3 (3.0)
Simple unilocular 0 0 0
Septation .289
Multiple 67 (58.3) 6 (40.0) 61 (61.0)
Single 9 (7.8) 2 (13.3) 7 (7.0)
None 39 (33.9) 7 (46.7) 32 (32.0)
Vascularity of septation .088
No 40 (34.8) 7 (46.7) 33 (33.0)
Yes 36 (31.3) 1 (6.7) 35 (35.0)
NA 39 (33.9) 7 (46.7) 32 (32.0)
Solid area other than septation .345
No 3 (2.6) 1 (6.7) 2 (2.0)
Yes 112 (97.4) 14 (93.3) 98 (98.0)
Vascular flow in solid component .466
No 26 (22.6) 3 (20.0) 23 (23.0)
Yes 86 (74.8) 11 (73.3) 75 (75.0)
NA 3 (2.6) 1 (6.7) 2 (2.0)
Morphology of the solid areas .032
Entire mass is solid 17 (14.8) 4 (26.7) 13 (13.0)
Irregular and/or papillary 85 (73.9) 7 (46.7) 78 (78.0)
Smooth 10 (8.7) 3 (20.0) 7 (7.0)
NA 3 (2.6) 1 (6.7) 2 (2.0)
Ascites 1.000
None or mild 104 (90.4) 14 (93.3) 90 (90.0)
Moderate or severe 11 (9.6) 1 (6.7) 10 (10.0)
Data are presented as number (percentage), unless otherwise indicated.
NA, not applicable.
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.

Although the optimal schedule of ul-
trasound examination follow-up has not
been defined, studies indicate that many
masses require several months to resolve;
as such, a longer time interval has a
higher likelihood of demonstrating res-
olution.17 The observation that a mass is
stable is also more meaningful the longer
the time interval. However, repeated ul-
trasound examinations may increase the
likelihood of incidental findings. In our
setting, clinical management decisions
are supported by a standardized ultra-
sound reporting system that stratifies
masses as low, intermediate, or high risk
based on ultrasound characteristics.9 In
the absence of other clinical indicators of
malignancy, such as elevated CA 125
tumor markers, postmenopausal women
with masses considered low risk undergo
limited follow-up with repeat ultrasound
examination at 6 weeks and 6 months,
whereas those with intermediate risk
have repeat ultrasound examination at 6
weeks and 3, 6, 12, and 24 months. In-
dividuals with masses with high-risk
characteristics, which we define as solid
areas larger than 1 cm and abnormal
vascular flow, are referred to gynecologic
oncology.

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TABLE 3
Ultrasound characteristics of adnexal masses associated with stage I vs stage II high-grade serous cancer
Variables Total (N¼115) Stage I (n¼65) Stage II (n¼50) P value
Age 1.000
MeanSD 61.811.4 61.811.2 61.811.9
Mass size .370
MeanSD 10.54.7 10.85.1 10.04.1
MinimumeMaximum 2.2e23.6 2.2e23.6 3.3e20.7
Median (IQR) 9.6 (6.8e13.6) 10.9 (6.9e14.5) 9.4 (6.8e13.2)
Race and ethnicity .416
White 71 (61.7) 41 (63.1) 30 (60.0)
Black 9 (7.8) 6 (9.2) 3 (6.0)
Hispanic non-Black 13 (11.3) 7 (10.8) 6 (12.0)
Asian or Pacific Islander 19 (16.5) 8 (12.3) 11 (22.0)
Other 3 (2.6) 3 (4.6) 0 (0)
Appearance .286
Mixed cystic and solid 89 (77.4) 53 (81.5) 36 (72.0)
Multilocular 6 (5.2) 4 (6.2) 2 (4.0)
Solid 17 (14.8) 6 (9.2) 11 (22.0)
Nonsimple unilocular 3 (2.6) 2 (3.1) 1 (2.0)
Simple unilocular 0 (0) 0 (0) 0 (0)
Septation .404
Multiple 67 (58.3) 37 (56.9) 30 (60.0)
Single 9 (7.8) 7 (10.8) 2 (4.0)
None 39 (33.9) 21 (32.3) 18 (36.0)
Vascularity of septation .915
No 40 (34.8) 23 (35.4) 17 (34.0)
Yes 36 (31.3) 21 (32.3) 15 (30.0)
NA 39 (33.9) 21 (32.3) 18 (36.0)
Other solid components .256
No 3 (2.6) 3 (4.6) 0 (0)
Yes 112 (97.4) 62 (95.4) 50 (100.0)
Vascular flow in solid components .193
No 26 (22.6) 17 (26.2) 9 (18.0)
Yes 86 (74.8) 45 (69.2) 41 (82.0)
NA 3 (2.6) 3 (4.6) 0 (0)
Morphology of the solid areas .123
Entire mass is solid 17 (14.8) 6 (9.2) 11 (22.0)
Irregular and/or papillary 85 (73.9) 51 (78.5) 34 (68.0)
Smooth 10 (8.7) 5 (7.7) 5 (10.0)
NA 3 (2.6) 3 (4.6) 0 (0)
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021. (continued)

1.e6 American Journal of Obstetrics & Gynecology MONTH 2021

ajog.org
TABLE 3
Ultrasound characteristics of adnexal masses associated with stage I vs stage II high-grade serous cancer (continued)
Variables
Ascites
None or mild
Moderate or severe
IQR, interquartile range; NA, not applicable; SD, standard deviation.
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.
In addition, observation is generally
reserved for asymptomatic women,
whereas most of the women with early-
stage cancer in this study were symp-
tomatic with only 12% of cases being
detected because of incidental findings
on imaging. The 3 most common in-
dications for ultrasound examination
were abdominal pain, a palpable mass on
examination, and postmenopausal
bleeding, which is consistent with a
previously published study that
FIGURE 3
Representative ultrasound images and characteristics
Suh-Burgmann et al. Ultrasound appearance of early-stage ovarian cancer. Am J Obstet Gynecol 2021.
Total (N¼115) Stage I (n¼65)
104 (90.4)
11 (9.6)
compared the clinical presentations of
women with early- and late-stage
ovarian cancers. In that study, a
palpable mass and postmenopausal
bleeding were the only 2 presenting
symptoms more likely to be associated
with early-stage vs late-stage ovarian
cancer diagnosis.18
Research implications
Although many high-grade serous can-
cers metastasize early, leading 80% of
GYNECOLOGY Original Research
Stage II (n¼50) P value
.010
63 (96.9) 41 (82.0)
2 (3.1) 9 (18.0)
women to be diagnosed at advanced
stages, our findings suggest that there
may be a subset that grows confined to
the ovary for a prolonged period and is
therefore amenable to early-stage detec-
tion. The observation that a completely
solid appearance was more common
among smaller than larger masses also
suggest that the ultrasound appearance
of some cancers may evolve from a pre-
dominantly solid appearance to a more
cystic and solid appearance as the tumor
grows.
Strengths and limitations
The strengths of the study include the
community-based, well-characterized
and diverse nature of the cohort, which
increased the generalizability of our
findings to other community settings.
Despite the rarity of clinically detected
early-stage high-grade serous cancer, the
ability to draw from 10 years of experi-
ence in a large integrated health system
setting enabled the identification of these
women and their preceding ultrasound
studies. Ultrasound examinations were
independently scored by 3 radiologists,
reducing the potential impact of a single
individual’s style or preferences on ul-
trasound characterization. The limita-
tions of the study included its
retrospective nature and that the radi-
ologists were not blinded to the fact that
these were ultrasound examinations of
women who had been diagnosed with
cancer, which may have influenced their
ultrasound scoring. The quality of ul-
trasound examinations also varied,
limiting the ability to assess all charac-
teristics equally across patients. As our
study evaluated only high-grade serous
cancers, our conclusions regarding the
safety of observation related only to the
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Original Research GYNECOLOGY
risk of missing a high-grade serous can-
cer, not other ovarian cancer subtypes.
However, unlike high-grade serous can-
cer, the other common histologic types
of ovarian cancer (endometrioid, clear
cell, mucinous) usually come to clinical
attention at the early stage because of
their tendency to grow to a large size
before metastasizing.19 Finally, the study
did not establish what the earliest
detectable ultrasound abnormality of
these tumors potentially could have
been but rather reports what it was in
actual practice. Apart from the
described exclusions, all clinically
detected high-grade serous cancers and
all ultrasound examinations performed
within a year of diagnosis were included
in the study. Therefore, although it is
possible that these cancers could have
come to clinical attention when smaller,
they simply did not, suggesting that the
only way to have detected them when
small would have been by screening
asymptomatic women. Unfortunately,
the negative results from randomized
controlled trials of ovarian cancer
screening indicate that this is not an
effective strategy.
Conclusion
In this community-based setting, early-
stage high-grade serous cancers rarely
presented as masses of <5 cm or masses
without solid areas other than septations
on ultrasound examination. Our find-
ings provide additional support for the
observation of small masses that do not
demonstrate solid areas other than sep-
tations on ultrasound examination. n
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Author and article information
From the Division of Gynecologic Oncology, The Perma-
nente Medical Group, Oakland, CA (Dr Suh-Burgmann);
Division of Research, Kaiser Permanente Northern Cali-
fornia, Oakland, CA (Drs Suh-Burgmann and Hung);
Department of Radiology, The Permanente Medical
Group, Oakland, CA (Dr Brasic); and Department of
Radiology, University of California, San Francisco, San
Francisco, CA (Ms Jha and Dr Goldstein).
Received March 1, 2021; revised April 28, 2021;
accepted April 30, 2021.
This study was funded by the Kaiser Permanente
Northern California Community Benefit Research Pro-
gram and the Permanente Medical Group Physician
Researcher Program.
The authors report no conflict of interest.
Corresponding author: Elizabeth Suh-Burgmann, MD.
Betty.Suh-Burgmann@kp.org