Assessing the risk of ovarian malignancy algorithm for the conservative management of women with a pelvic mass

Highlights

• ROMA with clinical assessment identifies women with a who can be managed conservatively 1/3 of women initially referred for surgery were able to undergo conservative management.

• ROMA helps triage women with a pelvic mass for non-sugical follow up.

Abstract

Objective

To evaluate the use of as an aid in the identification of women who can safely undergo conservative, non-surgical management.

Methods

All patients referred to the Program in Women's Oncology for surgery with a pelvic mass are evaluated at a prospective multidisciplinary tumor board (TB) where ROMA and imaging are used for management recommendations. This study evaluated women presented to TB with a pelvic mass between 2009 and 2013 who had either surgical or conservative management.

Results

Of the 498 patients assessed, 392 (79%) had benign disease, 22 (4%) had LMP tumors, 28 (6%) had stage I-II epithelial ovarian cancer (EOC), 36 (7%) had stage III-IV EOC and 20 (4%) had non-EOC. Using clinical assessment in conjunction with ROMA, the TB recommended observation in 188 (37.8%) women. All patients diagnosed with an invasive malignancy were recommended for surgery by the TB. In the 315 patients managed surgically, 212 were found to have benign disease and 84 women were diagnosed with an invasive malignancy. The sensitivity for the initial TB recommendations using ROMA in conjunction with clinical judgment for detecting malignancy was 100% with a specificity of 47.7% and a NPV of 100%. When including low malignant potential tumors the sensitivity was 99.1%. For stage I-IV EOC ROMA alone had a sensitivity of 95.3%.

Conclusions

ROMA in conjunction with clinical assessment can safely identify women for conservative management.

Introduction

In the United States, approximately 289,000 women are hospitalized each year with an ovarian cyst or pelvic mass. Although the majority of these women will be diagnosed with benign disease, 5–10% will be diagnosed with an ovarian cancer [1], [2]. Obtaining a biopsy is technically challenging and discouraged in patients with presumed early stage disease, as the risk for rupture and dissemination of potentially malignant cells is a concern. The most reliable way to rule out a malignancy is with surgery and pathologic examination, which carries significant risk for morbidity, costs and potentially unnecessary major surgery. It is estimated that, in the United States, women have a 5–10% lifetime risk of undergoing surgery for a suspected ovarian neoplasm [3]. Many of the procedures performed to evaluate a pelvic mass ultimately identify a benign process. In a large ovarian cancer screening trial, 20 cases (3.5%) of malignancy were found among 570 women who underwent surgical evaluation for suspected ovarian cancer [4]. Therefore, improving methods for distinguishing benign from malignant masses would avoid unnecessary surgeries.

Management guidelines put forth by the American College of Obstetricians and Gynecologists (ACOG) recommend that surveillance is appropriate for adnexal masses in asymptomatic premenopausal women with specific sonographic characteristics, and that in postmenopausal women, the combination of ultrasound and CA125 measurements should be used to guide decision making [5]. ACOG suggests that in postmenopausal women, most pelvic masses, with the exception of sonographically simple appearing cysts, will require surgical intervention, and that any elevation of CA125 is suspicious for malignancy [6], [7]. For the detection of malignancy, the use of imaging alone, including ultrasonography, CT and MRI provides a sensitivity in the range of 82–91% and the use of CA125 measurement alone has a sensitivity ranging from 78% [8], [9].

Biomarkers or panels of biomarkers are generally used in combination with each other or with imaging and clinical findings to aid in the diagnosis of epithelial ovarian cancer (EOC). The Risk of Ovarian Malignancy Algorithm (ROMA) is a logistic regression algorithm that utilizes the serum biomarkers HE4 and CA125 along with menopausal status to assess the risk that an ovarian cyst or pelvic mass is benign or malignant [10], [11]. ROMA has been validated to have a high sensitivity, specificity and negative predictive value in multiple multicenter prospective trials for predicting the presence of ovarian cancer in women with a pelvic mass. The combined HE4 and CA125 algorithm was found to be highly accurate in assigning patients to risk groups, with 95% of epithelial ovarian cancers correctly classified as high risk [11], [12], [13]. These trials led to USFDA clearance for ROMA as a test to assist in triaging high risk patients to a gynecologic oncologist and is becoming a tool that is increasingly being utilized by gynecologists and other physician specialists for pelvic mass risk assessment. However, ROMA has not yet been studied or approved as a guide for the conservative management of women with a pelvic mass.

The purpose of this study was to evaluate the use of ROMA in women with an adnexal mass to assist in identifying women at low risk for malignancy who can safely undergo conservative, non-surgical, management.