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The best strategy for identifying pelvic masses and triaging patients to the appropriate surgeons.
Illustration by Alex Baker, DNA Illustrations, Inc.
Approximately 20% of women will develop a pelvic mass at some time in their lives.1 Pelvic masses present gynecologists with difficulties in both diagnosis and management. When a patient presents with a pelvic mass, the gynecologist needs to first determine if the mass is gynecologic in origin and then determine whether it is benign or malignant. This article aims to aid physicians in the workup of pelvic masses and triage of patients with pelvic masses to the appropriate surgeon for optimal care.
Perhaps the most difficult challenge for reducing ovarian cancer mortality is the lack of effective screening. Patients with a personal lifetime risk of ovarian cancer of greater than 20% to 25% should undergo genetic testing. Women with a personal lifetime risk of 5% to 10% should be offered genetic testing.2 Women with BRCA mutations can be offered prophylactic measures to prevent ovarian cancer.
Aside from genetic testing, no standard screening method has been shown to decrease mortality rates from ovarian cancer. The screening program with the most data is the use of only serial CA-125 measurements at regular intervals to calculate a Risk of Ovarian Cancer Algorithm (ROCA) score, thereby determining whether a patient is at increased risk of ovarian cancer.3 An elevated ROCA score triages patients to transvaginal ultrasonography (TVS) for a determination about whether further management is necessary. In a recent study, more than 4000 women at average risk of ovarian cancer had a baseline CA-125 level determined and ROCA score calculated.4 If the score indicated low risk, patients were triaged to repeat CA-125 measurement in 1 year. Intermediate-risk women had CA-125 measurement repeated in 3 months and those at high risk underwent TVS and were referred to a gynecologic oncologist. The outcomes of this study demonstrate that the ROCA algorithm had a sensitivity of 40% and a specificity of 99.9% for detecting invasive ovarian cancer.4
The Prostate, Lung, Colorectal, and Ovarian Trial used CA-125 and TVS to predict risk of ovarian cancer. Of the 22,955 women in the intervention group, 1771 (7.7%) underwent oophorectomy because of abnormal screening findings. Of the 22,542 women in the usual care group, 1304 (5.8%) underwent oophorectomy because of abnormal screening findings. Of the women with abnormal findings on screening, only 1% had invasive ovarian cancer, and screening with CA-125 and TVS did not reduce mortality.5 Clearly, an ovarian cancer screening tool is very much needed that can be used to assess risk in the general population.
Because no universal screening for ovarian cancer currently exists, most gynecologists are faced with the challenge of determining the nature of a pelvic mass discovered on exam or imaging. The initial workup of a pelvic mass in a woman of reproductive age should include a pregnancy test. Once pregnancy is ruled out, the site of origin of the mass should be determined. Pelvic masses of nongynecologic origin include masses of the gastrointestinal and urinary tract. Patients with nongynecologic masses should be referred to the appropriate consultant.
For gynecologic pelvic masses, the uterus, fallopian tubes, and ovaries should all be considered possible sites of origin. Management of the majority of pelvic masses is relatively straightforward, whereas management of adnexal masses tends to be more difficult.
For women with adnexal masses, optimal care requires differentiating benign from malignant conditions. Although metastatic disease from other primary sites needs to also be ruled out, this review will focus on primary ovarian malignancies. One woman in every 72 in the United States will develop ovarian cancer during her lifetime.6 In the United States, a woman has a 5% to 10% lifetime risk of undergoing surgery for suspected ovarian cancer, and among those who undergo such surgery, the likelihood of being diagnosed with ovarian cancer is 13% to 21%.7
Workup for a pelvic mass begins with a careful history and physical examination. Although ovarian cancer has long been considered an asymptomatic “silent killer,” recent studies have shown that certain symptoms may help diagnose ovarian cancer. These include symptoms of bloating, increased abdominal size, pelvic or abdominal pain, difficulty eating, and early satiety, which have a sensitivity of 80% in detecting advanced-stage ovarian cancer and 57% in detecting early-stage disease.8 Other symptoms that are concerning for less common ovarian tumors are abnormal uterine bleeding, breast tenderness, and precocious puberty, which can be seen in granulosa cell tumors or thecomas, and hirsutism, deepening of the voice, and other symptoms of excess testosterone, which can be suggestive of a Sertoli-Leydig tumor. Fever and vaginal discharge can suggest a tubo-ovarian abscess, while dysmenorrhea, dyspareunia, and dyschezia suggest endometriosis or an endometrioma.
Physical examination includes a general assessment, including assessment for signs of cachexia, virilization, or hyperestrogenism. A lymphatic survey should be performed, including palpation of supraclavicular, axillary, and inguinal lymph nodes. An abdominal examination should be done to assess for pain, palpable masses, omental caking, and possible fluid wave suggestive of ascites. The pelvic examination should begin with a speculum examination to assess for recent bleeding and for position of the cervix, as it may be displaced by a large pelvic mass. If a mass is palpable on pelvic examination, it should be characterized in terms of contour, firmness, size, location, and mobility.
Lastly, rectovaginal examination should be done to palpate the uterosacral ligaments and cul-de-sac to assess for the presence of metastatic disease, nodularity, or obliteration of the cul-de-sac. As a general rule, physicians tend to underestimate the size of a mass palpated on pelvic examination. Pelvic examination has a sensitivity of only 45% in the detection of pelvic masses.9 This underscores the need for physicians to be aware of the limitations of pelvic examination, especially in obese patients.
Consideration of ovarian cancer risk factors
The symptoms of ovarian cancer are often vague, but risk factors may be useful in determining a patient’s risk of malignancy. Age is the most important risk factor in the general population. The incidence of ovarian cancer increases after menopause, and the median age at diagnosis is 63 years.10
Family history of breast or ovarian cancer increases the lifetime risk of ovarian cancer. Women who have BRCA1 mutations have a 40% lifetime risk and those with BRCA2 mutations have a 20% lifetime risk of developing ovarian cancer.2 Women with hereditary nonpolyposis colorectal cancer (Lynch syndrome) have a 13-fold increased risk of ovarian cancer compared to the general population.7
Other risk factors for ovarian cancer include nulliparity, primary infertility, endometriosis, early menarche, late menopause, white race, and residence in North America, Northern Europe, or any industrialized Western country.
Several factors have been associated with a reduced risk of developing ovarian cancer, including tubal ligation, hysterectomy, multiparity, and use of oral contraceptives (OCs). Large studies have found up to a 40% reduction in ovarian cancer risk in women who used OCs at any point in their lives for any amount of time. A 90% reduction in risk was seen in women who used OCs for longer than 15 years.7
Imaging for pelvic masses typically begins with TVS. Sonography has the advantages of being widely available, well tolerated by patients, and cost-effective. The major limitation is its lack of specificity for diagnosing cancer. Mass characteristics that should be assessed include size, blood flow, location, locularity, and echogenicity.11,12 Findings suggestive of malignancy include excrescences, ascites, complex or solid components, bilateral tumors, mass larger than 10 cm in diameter, and mural nodules.11
Various scoring systems have been established to distinguish benign from malignant masses on sonography. DePriest and colleagues developed a system that used 3 criteria (tumor volume, cyst wall structure, and septa structure) and assigned a score to each criterion based on measurements.13 High intraobserver variation was found in utilization of the scoring system, particularly in assigning scores for cyst wall structure and septa structure.
Color Doppler sonography is used to evaluate pelvic masses because hypoxic tissue in tumors will often undergo angiogenesis and, therefore, a “chaotic” vascular architecture correlating with malignancy may be seen.14 If the malignant potential of a pelvic mass is indeterminate on sonography, magnetic resonance imaging can be used to further characterize the mass. Computed tomography scan is recommended when there is high suspicion of malignancy to aid in preoperative staging and determining disease resectability.
NEXT: ASSESSMENT OF TUMOR MARKERS >>
Assessment of tumor markers
Once imaging reveals the malignant potential of a pelvic mass, assessment of tumor markers can aid in determining the diagnosis (Table). Tumor markers are helpful for both establishing the diagnosis and monitoring response to treatment. When considering which tumor marker studies to order, physicians should take into account patient age, symptoms, physical examination findings, and imaging findings.
In women younger than age 30 years, physicians should consider assessing tumor markers for germ cell tumors, such as α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase, and tumor markers for sex-cord stromal tumors, such as inhibin A and B, estradiol, and testosterone. For women aged 30 to 50 years, inhibin A and B, estradiol, and testosterone and CA-125 are suggested, whereas in women older than age 50 years, CA-125, CA 19-9, inhibin A and B (if symptoms), and carcinoembryonic antigen are recommended.
CA-125 is the most well-known and widely accepted tumor marker for ovarian cancer. In premenopausal patients, CA-125 is a poor screening test because CA-125 level elevations can be associated with endometriosis, adenomyosis, retrograde menstruation, and pelvic inflammatory disease and will often fluctuate with the menstrual cycle. The most widely accepted use of CA-125 testing is as an adjunct to imaging in postmenopausal women with an ovarian mass in order to distinguish benign from malignant masses.
Human epididymis 4 protein (HE4) has shown potential in successfully identifying patients with ovarian cancer, especially when used in combination with CA-125. In one large study, CA-125 plus HE4 successfully identified 94% of patients with epithelial ovarian cancer as high risk.15
Several commercial tests have been specifically designed to determine the malignant potential of pelvic masses and guide patient referral. One of the most commonly used tests for preoperative evaluation of malignant potential of a pelvic mass is the OVA1 test, which was approved for use in 2009.16 OVA1 combines CA-125, transthyretin, transferrin, β-microglobulin, and apolipoprotein A1 and generates a single-number result. In a study in 516 women with an adnexal mass, the combination of the OVA1 test and physical assessment had a sensitivity of 96% in predicting malignancy, compared to only 75% for physical assessment alone and 93% for the OVA1 test alone. The specificity, however, was much lower, at 35% for combined OVA1 test and physical assessment. Similarly, the combined approach had a high negative predictive value of 95% but a low positive predictive value of only 35%.17
Before treating a pelvic mass, assessing risk of malignancy is of utmost importance so that patients can be referred to the most appropriate surgeon and facility for optimal care. Survival in women with ovarian cancer is closely associated not only with stage but also with the treating surgeon and the treatment facility. Sixty-eight percent of women with ovarian cancer have late-stage disease upon diagnosis, and the 5-year survival rate in this group is 30%.18 Women with ovarian cancer who undergo surgery for ovarian cancer have over a 1-year improvement in survival if they are referred to a gynecologic oncologist for tumor debulking.19,20 In addition, women with ovarian cancer who are referred to a high-volume expert cancer center have improved overall survival. This is especially true in those with advanced-stage ovarian cancer. Treatment requires both surgery and chemotherapy, which are best executed by an experienced multidisciplinary team.21 Bristow and colleagues investigated the quality of care in patients with ovarian cancer by evaluating adherence to National Comprehensive Cancer Network (NCCN) guidelines. High-volume physicians were more likely to perform proper surgery, administer correct chemotherapy, and deliver appropriate treatment to ovarian cancer patients than low-volume physicians. There was a statistically significant difference seen in the 5-year disease-specific survival rates between patients receiving adherent versus nonadherent NCCN care.22
Despite the benefits of treatment by a subspecialist, more than 50% of patients with ovarian cancer are never seen by a gynecologic oncologist.19 The American Congress of Obstetricians and Gynecologists in conjunction with the Society of Gynecologic Oncologists has developed guidelines for referral of patients with pelvic masses to a gynecologic oncologist.7
Patients with adnexal masses can be divided into 3 categories: low risk, intermediate risk, and high risk of malignancy.23 The likelihood of malignancy depends on a variety of clinical, genetic, and epidemiologic factors, as outlined earlier in this article. The risk of malignancy is used to decide whether surgery is warranted.
In women with low-risk adnexal masses, defined as those associated with a <1% risk of malignancy, tests with low specificity, such as CA-125, should be avoided. These masses are generally asymptomatic. One example of a low-risk adnexal mass is a simple ovarian cyst. Although no conclusive follow-up protocol has been identified, the general recommendation is sonography at 3- to 6-month intervals.23
Intermediate-risk adnexal masses pose a risk of malignancy of greater than 1%. The majority of these masses are benign; examples include endometriomas, hemorrhagic cysts, hydrosalpinges, and other benign ovarian neoplasms. When surgical intervention is considered, the morbidity associated with surgery must be weighed against delay in diagnosis of a potential malignancy. The theoretical benefits to surgery that might help the physician and patient come to a decision include prevention of torsion and cyst rupture.
High-risk adnexal masses always require surgical intervention because findings are highly suggestive of malignancy.23 If the primary surgery is not performed by a gynecologic oncologist, a second operation for inadequate staging or cytoreduction may be necessary, increasing potential morbidity and delaying adjuvant therapy.
Once the needs for surgery has been determined, the surgical approach to a pelvic mass must be addressed. Laparotomy with vertical midline incision is recommended for any patient with an obvious malignancy, and complete staging should be performed. Optimal cytoreduction of residual disease has shown survival benefit in women with advanced-stage ovarian cancer. In high-volume cancer centers with experienced surgeons, upper abdominal debulking procedures-including diaphragm stripping, splenectomy, distal pancreatectomy, liver wedge resection, excision of porta hepatis tumor, and cholecystectomy-significantly increase the rate of optimal cytoreduction.24
If a patient has a suspected benign pelvic mass, laparoscopy is preferred. Laparoscopy should be individualized and take into account the surgeon’s skill level, the size of the mass, and the patient’s surgical history. Rupture of a pelvic mass and dissemination of the cystic contents should be avoided to prevent upstaging of malignancy because studies have shown that intraoperative rupture of stage I ovarian cancer incurs a worse prognosis for the patient.25 In the absence of apparent malignant disease, a frozen section should be sent to pathology for intraoperative consultation. If a general gynecologist is performing the surgery and malignancy is confirmed, a gynecologic oncologist should be consulted intraoperatively.
NEXT: SPECIAL CIRCUMSTANCES >>
Various circumstances can make intraoperative decision-making regarding management of pelvic masses difficult. One of these circumstances is the presence of a borderline tumor. If a borderline tumor is diagnosed during intraoperative pathology consultation, the traditional recommendation is for complete surgical staging, although more recent data suggest this might not be necessary.26,27 For patients who desire fertility preservation, a simple cystectomy or unilateral salpingo-oophorectomy is acceptable, but patients should be informed that recurrence rates range from 10% to 30%.28 Frozen section has a high rate of inaccuracy in the diagnosis of borderline tumors, therefore, the final pathology report may be vastly different from the intraoperative report. For that reason, in women who desire future fertility, conservative management with retention of at least one ovary and the uterus should be considered.
A second special circumstance is the presence of a pelvic mass in pregnancy. The incidence of pelvic masses during pregnancy ranges from 2% to 10%, and most resolve spontaneously.29 Sonography each trimester and repeat sonography 6–8 weeks postpartum is indicated. Because most of these masses are benign, expectant management is appropriate except in the case of torsion or mass effect causing pain or obstructing labor. The most common histologies, in decreasing order of frequency, are dermoid cyst, cystadenoma, endometrioma, and functional cyst.29 Tumor marker levels are typically elevated as a result of pregnancy, thus tumor marker tests are not recommended.
The third special circumstance is a pelvic mass in a child or adolescent. Greater than 90% of these masses are benign, and most pelvic masses in children and adolescents can be managed expectantly with careful follow-up.30 If malignancy is suspected or torsion occurs, surgery is appropriate. Careful evaluation and management to preserve ovarian function is warranted.
Advances in technology, most notably imaging, now aid physicians in distinguishing benign from malignant pelvic masses, although no single modality is perfect. The ability of the physician to determine which patient needs surgery and which masses can be managed expectantly is of utmost importance. The combination of symptom assessment, imaging, tumor marker assessment, and physical examination helps physicians triage patients appropriately, which results in better outcomes for patients with a pelvic mass.
Dr. Lyons is a resident in the Department of Obstetrics and Gynecology, Houston Methodist Hospital, Texas.
Dr. Soliman is an Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston.
Dr. Frumovitz is an Associate Professor and Fellowship Program Director in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston.
Dr. Lyons and Dr. Soliman have no conflict of interest to disclose with respect to the content of this article.
Dr. Frumovitz reports receiving consulting fees from Novadaq.
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