American Journal of Obstetrics and Gynecology (2004) 190, 1435e7

www.elsevier.com/locate/ajog

Differences in symptoms between patients with benign

and malignant ovarian neoplasms
Cara A. Attanucci, MD, Harrison G. Ball, MD, Susan L. Zweizig, MD,
Annette H. Chen, MD*
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Massachusetts Medical
Center, Worcester
Received for publication September 11, 2003; revised December 31, 2003; accepted January 21, 2004

KEY WORDS
Ovarian cancer symptom
Early diagnosis

Objective: The purpose of this study was to determine the symptoms that are experienced by patients who receive a diagnosis of early ovarian cancer and to compare those symptoms with the
symptoms that are experienced by patients with late ovarian cancer, borderline ovarian cancer,
and benign ovarian neoplasms.
Study design: This study used a retrospective case-control design. Cases of invasive and borderline ovarian cancer (n = 147 patients) were compared with 76 patients with benign ovarian neoplasms.
Results: Patients with early ovarian cancer were signicantly more likely to have symptoms of
mass eect (urinary frequency, constipation, palpable mass, pelvic pressure) compared with patients with benign ovarian neoplasms (67% vs 15%; P!.001), late stage disease (67% vs 40%;
P = .008), and borderline cancer (67% vs 33%; P = .007).
Conclusion: Mass eect symptoms were the only symptoms that dierentiated patients with earlystage ovarian cancer from all other groups of patients. However, one third of the patients with
early ovarian cancer did not report any of these symptoms.
2004 Elsevier Inc. All rights reserved.

In 2003, an estimated 25,400 women will be diagnosed with ovarian cancer in the United States and an
estimated 14,300 women will die of the disease.1 Understanding symptoms of early ovarian cancer may help
clinicians and patients to identify ovarian cancer at an
earlier more curable stage.

* Reprint requests: Annette H. Chen, MD, 119 Belmont St,

Worcester, MA 01605.
E-mail: chena@ummhc.org
0002-9378/$ - see front matter 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajog.2004.01.077

Several small retrospective chart reviews and one

large national survey have examined the symptoms of
ovarian cancer.2-6 These studies suggest that nearly all
patients who have ovarian cancer, regardless of stage,
are symptomatic and that the predominant symptoms
are gastrointestinal and constitutional.
The major limitation of these retrospective studies is
the reliance on postdiagnosis techniques to identify
symptoms, which introduces recall bias. Furthermore,
these studies compared women with ovarian cancer with
population-based control subjects. The purpose of this
study was to compare the symptoms that are experienced

1436
Table I

Attanucci et al
Patient characteristics

Characteristic
Average
age (y)*
Parity (n)y
Patients with
history of breast
cancer (%)
Postmenopausal (%)
Previous hormone
replacement
therapy use (%)
Any oral
contraceptive
pill use (%)

Ovarian
cancer

Borderline
tumors

Benign
tumors

62 (21-85)

50 (20-86)

49 (15-81)

2.4 G 2
7.9

2.1 G 2.5
0

2.2 G 1.8
1.3

78.1
23.7

42.4
9.1

44.7
21.1

26.3

42.4

52.6

* Data in parentheses represent range.

y
Data are given as mean G SD.

by patients who have been diagnosed with early ovarian

cancer with patients who have late-stage, borderline, and
benign ovarian neoplasm.

Material and methods

With the use of a retrospective case-control design, 147
cases of invasive and borderline ovarian cancers that
were diagnosed between January 1, 1999, and December
31, 2001, were identied by the tumor board registry and
ICD-9 codes. During the same time period, based on
ICD-9 codes, 172 patients were referred to the senior author for adnexal masses. Of these, 77 patients did not
have pathology reports that conrmed an adnexal mass;
11 patients were not treated within the selected time period; 6 patients had cancer and were already on the case
list; 2 patients had germ cell tumors, and 76 patients had
benign ovarian neoplasms and were selected to serve as
control subjects. Operative reports and pathology reports were reviewed to verify the diagnosis and stages.
Tumor size was dened as the largest dimension of the
adnexal mass in the gross disease description. Cases with
incomplete surgical staging (n = 35 women) were excluded. All patients underwent routine history and physical examination before surgery. This initial consultation
visit was used to identify symptoms. Chi-squared test,
Fischers exact test, and multiple t-tests with Bonferroni
correction were used as appropriate. A probability value
of !.05 was considered signicant.

Results
There were 114 patients with ovarian cancer: 33 patients
(29%) had early stage disease (I and II), and 81 patients

(71%) had late stage disease (III and IV). There were 33
patients with borderline ovarian cancer, 29 patients
(88%) with early stage disease, and 4 patients (12%)
with late stage disease. The 76 control subjects had
serous cystadenomas (26%), endometriomas (17%), bromas (15%), dermoids (13%), and other (29%). Patient characteristics are summarized in Table I. Nearly
all patients reported at least one symptom (Table II).
There was no signicant difference in the number of
asymptomatic patients among any of the groups.
Patients with early ovarian cancer were signicantly
more likely to report symptoms of mass effect (frequency, constipation, palpable mass, pelvic pressure;
67% vs 15%; P!.001), and less likely to have constitutional symptoms (9% vs 29%; P = .023) compared with
patients with benign ovarian neoplasms. There were no
signicant differences among groups in gastrointestinal,
pain, or gynecologic symptoms.
Compared with patients with borderline cancers, patients with early-stage disease were signicantly more
likely to have symptoms of mass effect (67% vs 33%;
P = .007). There were no signicant differences in gastrointestinal, pain, constitutional, or gynecologic symptoms.
Compared with patients with late-stage disease, patients with early-stage disease were signicantly more
likely to report symptoms of mass effect (67% vs 40%;
P = .008) and gynecologic symptoms (46% vs 24%:
P = .020), but signicantly less likely to report gastrointestinal symptoms (30% vs 63%; P = .002). There
were no signicant differences in pain or constitutional
symptoms.
The mean tumor size (13.5 G 6.8 cm) of patients with
early-stage disease was signicantly larger than the
mean tumor size (9.0 G 6.3 cm) of patients with latestage disease (P = .004) and benign disease (7.8 G 5.2
cm; P!.001). There was no statistically signicant difference between mean tumor sizes of patients with
early-stage versus borderline tumors (Table III).

Comment
Most patients in this investigation reported at least one
symptom. Mass effect symptoms were the only symptoms that differentiated patients with early-stage ovarian cancer from all other groups of patients.
Interestingly, constitutional symptoms were not helpful
in differentiating early ovarian cancer from late ovarian
cancer, borderline cancer, or benign ovarian neoplasm.
In fact, patients with benign disease were more likely
to report constitutional symptoms than patients with
early ovarian cancer. However, one third of the patients
with early ovarian cancer did not report any symptoms
of mass effect.

1437

Attanucci et al
Table II

Patient symptoms

Symptom

Early ovarian
cancer: I/II (n)

Late ovarian
cancer: III/IV (n)

Borderline ovarian
tumors (n)

Benign ovarian
neoplasms (n)

Gastrointestinal
Pain
Constitutional*
Gynecologicy
Mass effectz
Asymptomatic

10
19
3
15
22
3

51
46
46
19
32
3

7
14
6
11
11
6

16
46
22
28
11
11

(30%)
(58%)
(9%)
(46%)
(67%)
(9%)

(63%)
(57%)
(57%)
(24%)
(40%)
(4%)

(21%)
(42%)
(18%)
(33%)
(33%)
(18%)

(21%)
(61%)
(29%)
(37%)
(15%)
(15%)

* Constitutional symptoms: Fatigue, fever, weight loss, weight gain.

y
Gynecologic symptoms: Irregular vaginal bleeding, vaginal discharge, dyspareunia, change in menstrual cycle, post coital bleeding.
z
Symptoms of mass effect: Urinary frequency, constipation, palpable mass, pelvic pressure.

Table III

Tumor size

Tumor

Early ovarian
cancer (I/II)

Late ovarian
cancer (III/IV)

Borderline
ovarian tumors

Benign
ovarian neoplasms

All patients

N
Average size (cm)
Minimum size (cm)
Maximum size (cm)

33
13.8
3.0
28.0

81
9.0
1.1
30.0

33
13.5
3.5
38.0

76
7.8
1.5
30.0

223
9.9
1.1
38.0

This difference in symptoms may reect a difference

in tumor biologic condition. Patients with early-stage
disease may have a biologically different tumor that is
less likely to metastasize, despite being larger, thereby
producing symptoms of mass effect. Patients with latestage disease may have tumors that metastasize while
the primary tumor is still small and therefore never produce symptoms of mass effect. The nding of larger
mean tumor sizes in early-stage disease compared with
late-stage disease supports this hypothesis. Alternatively, patients whose symptoms are recognized, either
by the patients themselves or their physicians, may be
those patients who receive a diagnosis at an earlier stage.
This study found that gastrointestinal symptoms were
signicantly more common in patients with late-stage
disease compared with early-stage disease. This nding
is different from most previous studies, which have
found both early- and late-stage disease to have similar
gastrointestinal symptom rates. This difference may reect a difference in methods. Previous studies used interviews and questionnaires that were conducted after the
diagnosis of cancer was made and may reect recall bias.
In this study, symptoms were obtained directly from the
patient report at the initial consultation, before a cancer
diagnosis had been established. This reliance on the initial consultation may bias the data because of patient

denial of symptoms, patient failure to report symptoms,

or physician error in recording patient symptoms.
This study raises an interesting question: Do patients
with early-stage ovarian cancer have different symptoms, which reect tumor biologic condition, or does
patient awareness of subtle symptoms lead to earlier diagnosis? Future studies will be directed at obtaining the
symptom data prospectively to attempt to answer this
question.

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