The Risk of Ovarian Malignancy Algorithm (ROMA) is a blood-test calculation used to estimate the likelihood that an adnexal or ovarian mass is malignant in women who are already being evaluated for a pelvic mass. ROMA combines two tumor markers—CA-125 and human epididymis protein 4 (HE4)—with menopausal status to classify risk. It is not an ovarian cancer screening test for people without a mass, and it cannot diagnose cancer by itself. Its most useful role is preoperative risk stratification: helping clinicians decide whether a patient with an adnexal mass should receive additional evaluation or be referred to a gynecologic oncologist. A high ROMA result means the marker pattern is more concerning for epithelial ovarian cancer in the population for which that assay was validated, but benign conditions, kidney function, age, smoking, and the type of ovarian tumor can affect the component markers. The score must be interpreted alongside ultrasound or other imaging, symptoms, examination findings, and the laboratory’s own assay-specific cutoff.
- ROMA combines CA-125, HE4, and menopausal status into an ovarian malignancy risk classification.
- It is intended for selected patients with an adnexal mass, not for screening the general population.
- A high ROMA score increases concern for epithelial ovarian cancer but does not establish a diagnosis.
- Cutoffs and score formats vary by laboratory and assay platform; use the interpretation on the actual report.
- Imaging and clinical findings remain essential, and suspicious masses may require evaluation by a gynecologic oncologist.
Table of Contents
- What the ROMA test is used for
- How CA-125, HE4, and menopause affect the score
- ROMA score ranges and what high risk means
- Accuracy and important limitations
- Why ROMA is not an ovarian cancer screening test
- How the blood test is performed and what can affect it
- What happens after a high or low ROMA result
What the ROMA test is used for
ROMA was developed to help classify the risk of ovarian malignancy in women who have an adnexal mass and are being considered for surgery. An adnexal mass is a growth near the uterus, usually involving an ovary or fallopian tube. Most adnexal masses are benign, but some are ovarian or related cancers.
The key clinical problem is deciding how concerning a mass is before surgery. Outcomes for ovarian cancer are better when appropriate patients receive specialist care, including surgery by teams experienced in gynecologic oncology. A risk tool can therefore be useful if it changes referral or surgical planning.
ROMA does not directly examine the mass. Instead, it uses blood levels of CA-125 and HE4 plus menopausal status. A mathematical algorithm produces a score or risk classification. The exact formula and reporting format depend on the commercial assay system.
ROMA is most relevant to epithelial ovarian cancer, the most common broad category of ovarian malignancy. It is less informative for certain nonepithelial tumors, borderline tumors, and other pelvic cancers. The test also cannot determine stage, grade, or whether a mass has spread.
A ROMA result should never be interpreted in isolation from pelvic imaging. Ultrasound features such as solid components, papillary projections, irregularity, blood flow, ascites, bilaterality, and size can materially change risk. Modern models such as the ADNEX system integrate detailed ultrasound information and may outperform tumor-marker algorithms in some settings.
The value of ROMA is therefore practical rather than definitive: it adds biochemical information to the preoperative assessment of a known mass.
How CA-125, HE4, and menopause affect the score
ROMA uses two serum tumor markers because each has strengths and weaknesses.
CA-125 is a protein that can be elevated in epithelial ovarian cancer, especially advanced disease. It is also raised in many noncancerous conditions. Menstruation, endometriosis, uterine fibroids, pregnancy, pelvic inflammation, liver disease, and other causes can increase CA-125. Early ovarian cancer may produce a normal value, so CA-125 alone is neither sensitive nor specific enough for diagnosis.
HE4 is another protein that is frequently elevated in epithelial ovarian cancer. Compared with CA-125, HE4 is less often elevated by endometriosis, which can improve specificity in some patients. However, HE4 is strongly affected by kidney function and also tends to rise with age. Smoking and some nonovarian diseases can increase it as well.
Menopausal status matters because the baseline probability and biology of ovarian malignancy differ before and after menopause. ROMA therefore uses separate equations or thresholds for premenopausal and postmenopausal patients.
These three inputs generate the final risk classification. The score does not mean that a particular percentage of tumor cells are malignant. It is an algorithmic estimate derived from marker concentrations and menopause category.
Because CA-125 and HE4 assays differ among manufacturers, ROMA should be calculated only by the validated laboratory system. Entering component values into an online formula can produce an incorrect result if the values came from a different platform, units, or calibration.
ROMA score ranges and what high risk means
ROMA reports generally classify a patient as lower or higher risk for epithelial ovarian malignancy. Some laboratories display a numeric score and a corresponding interpretation. The dividing threshold is different for premenopausal and postmenopausal women and can also differ by assay platform.
For example, one current laboratory implementation using a specific commercial method reports different numeric cutoffs for the two menopause groups. Other systems may display the score on another scale or express it as a percentage. For this reason, a ROMA number should not be labeled “normal” or “abnormal” using a cutoff taken from another laboratory.
A high-risk ROMA result means the combination of CA-125 and HE4, interpreted for the patient’s menopause status, resembles the pattern more commonly seen in epithelial ovarian cancer. It supports a more cautious preoperative plan and may strengthen the case for referral to a gynecologic oncologist.
A low-risk ROMA result lowers concern but cannot rule out malignancy. Some ovarian cancers do not produce much CA-125 or HE4, and some tumor subtypes are not well represented by the algorithm. A mass with highly suspicious imaging features still requires appropriate evaluation even if ROMA is low.
The result also should not be used to estimate stage. A very high score does not necessarily mean metastatic cancer, and a lower score does not establish early-stage disease. Staging requires surgical, pathological, and imaging information.
Systematic reviews published in recent years show that ROMA has useful overall diagnostic accuracy in women with adnexal masses, with pooled sensitivity and specificity generally in the 80% range or higher depending on the study population. That is clinically helpful but far from perfect, which is why ROMA remains an adjunct rather than a stand-alone diagnostic test.
Accuracy and important limitations
The performance of ROMA depends on who is being tested. Accuracy estimates from a surgical referral population cannot be applied directly to healthy people with no adnexal mass. This is one reason the intended-use population matters so much.
A 2026 systematic review and meta-analysis that included studies of premenopausal and postmenopausal women found good overall discrimination, with pooled sensitivity and specificity in the mid-to-high 80% range. Performance differed somewhat by menopause status and study design. A separate 2025 meta-analysis focused on postmenopausal women also supported meaningful diagnostic value.
False-positive results occur. Benign gynecologic disease may increase CA-125. Reduced kidney function can increase HE4, sometimes substantially. Older age, smoking, and nonmalignant inflammatory or organ disease can also influence the markers. A high ROMA in a patient with chronic kidney disease therefore deserves careful interpretation rather than an automatic assumption of ovarian cancer.
False-negative results also occur. Early-stage cancers may release low marker levels. Some mucinous ovarian cancers, germ-cell tumors, sex-cord stromal tumors, and borderline tumors may not fit the biomarker pattern for which ROMA performs best.
ROMA is also only one of several risk-stratification methods. The Risk of Malignancy Index uses CA-125, ultrasound findings, and menopausal status. Ultrasound-based IOTA models and the ADNEX model use detailed imaging features. Comparative studies suggest that high-quality ultrasound models can perform extremely well and may outperform ROMA in some centers.
The best test therefore depends on available expertise and the clinical question. A biomarker score should complement, not replace, a skilled ultrasound assessment.
Why ROMA is not an ovarian cancer screening test
ROMA should not be used to screen asymptomatic women who do not have a known adnexal mass. The test was not validated for that purpose, and the mathematics of screening make false positives a major concern when a disease is relatively uncommon in the general population.
Even highly accurate tests can perform poorly as population screening tools when disease prevalence is low. Many more people without cancer may test positive than people with cancer, leading to repeat testing, imaging, anxiety, and unnecessary surgery.
Major ovarian cancer screening studies have examined CA-125-based strategies and ultrasound, but no blood-marker approach has established a mortality benefit sufficient for routine population screening in average-risk women. ROMA does not solve that limitation.
Women with inherited high-risk conditions, such as certain BRCA1 or BRCA2 pathogenic variants or Lynch syndrome, need specialized risk-management advice. ROMA is not a substitute for genetic counseling, recommended risk-reducing strategies, or expert surveillance plans where applicable.
Symptoms should also be evaluated on their own merits. Persistent bloating, early satiety, pelvic or abdominal pain, increasing abdominal size, urinary urgency or frequency, or unexplained weight changes deserve clinical assessment when persistent or concerning. Ordering ROMA without imaging or a defined adnexal mass is not the appropriate first step.
The intended use is narrower: a woman has a mass, surgery is being considered, and the clinician wants additional information about the probability of epithelial malignancy before deciding who should manage the operation.
How the blood test is performed and what can affect it
ROMA requires a blood sample for CA-125 and HE4 measurement. Fasting is usually not the central issue, but patients should follow the specific laboratory instructions because collection and assay requirements can vary.
The clinician or laboratory must correctly classify menopausal status. Definitions can differ in women with prior hysterectomy, irregular periods, hormonal treatment, or medically induced menopause, so the ordering team should use the criteria required by the assay.
Kidney function deserves special attention because HE4 can rise when filtration is reduced. A high HE4 in chronic kidney disease may inflate the ROMA score even when no ovarian malignancy is present. Creatinine and estimated glomerular filtration rate can therefore provide important context.
CA-125 may fluctuate with menstruation and benign pelvic inflammation. Endometriosis is a particularly common reason for CA-125 elevation in premenopausal women. HE4 may help improve specificity in this setting, but it does not eliminate false positives.
Marker measurements should ideally come from the same validated platform used to calculate the ROMA result. A patient should not mix a CA-125 result from one laboratory with an HE4 result from another and attempt to calculate the score independently.
The laboratory report should identify whether the result falls into its lower- or higher-risk category. If the report does not explain the cutoff, the ordering clinician can confirm the assay’s intended-use criteria and interpretation.
What happens after a high or low ROMA result
A ROMA result changes risk; it does not finish the diagnosis.
If ROMA is high, the clinician reviews the imaging and the overall probability of malignancy. A complex or highly suspicious mass, ascites, evidence of spread, elevated markers, or concerning symptoms may prompt referral to a gynecologic oncologist. Specialist involvement before the first operation can be important when ovarian cancer is a realistic possibility because staging and tumor-removal surgery are technically specialized.
If ROMA is low and ultrasound findings also look benign, management may involve observation, repeat imaging, or surgery by a general gynecologist depending on symptoms, mass size, age, and other factors. A low score should not overrule a mass that is enlarging, symptomatic, or morphologically suspicious.
When surgery occurs, pathology provides the definitive diagnosis. If cancer is found, pathology identifies tumor type and grade, and surgical or imaging findings determine stage. CA-125 and sometimes HE4 may then be used in follow-up for selected cancers, but that is a different use from the preoperative ROMA calculation.
Patients should ask three practical questions about a ROMA report: Was this test used because I have an adnexal mass? Which assay-specific cutoff applies to my menopausal status? How does the result fit with the ultrasound findings?
Those questions keep the score in its proper role. ROMA is useful when it improves preoperative triage, but the safest decision comes from combining biochemical markers, high-quality imaging, clinical judgment, and—when indicated—gynecologic oncology expertise.
Menopausal classification deserves attention because it is not always obvious. A woman who has had a hysterectomy may no longer have menstrual periods even though her ovaries remain hormonally active. Hormonal contraception, perimenopause, ovarian suppression, and prior cancer treatment can also blur the usual definitions. Laboratories or test manufacturers may specify how menopause should be assigned in these situations, and the correct category is necessary for a valid ROMA interpretation.
It is also useful to separate a marker abnormality from a mass abnormality. A benign-appearing simple cyst with a mildly abnormal marker pattern does not automatically carry the same risk as a complex solid mass with ascites. Likewise, a highly suspicious ultrasound should not be downgraded solely because ROMA is below the laboratory’s high-risk threshold. The strongest preoperative assessment uses concordant information from imaging, marker results, symptoms, age, and specialist examination.
For patients, the practical output of ROMA is not a treatment recommendation but a triage signal. The question is whether the probability of epithelial malignancy is high enough that surgery should be planned with gynecologic oncology expertise available from the start.
If a mass is followed rather than removed, ROMA is not usually repeated on a fixed schedule simply to “watch the number.” Follow-up is driven primarily by the lesion’s imaging appearance, growth, symptoms, and the clinician’s assessment of malignancy risk. Repeating CA-125 or HE4 may be useful in selected situations, but a changing biomarker does not substitute for repeat ultrasound when the anatomy itself needs reassessment.
This distinction helps avoid overtesting: ROMA is designed to improve a preoperative referral decision, not to become a lifelong ovarian cancer marker for every benign cyst.
References
– The risk of ovarian malignancy algorithm for ovarian cancer in premenopausal and postmenopausal women: A systematic review and meta-analysis 2026 (systematic review and meta-analysis) – Diagnostic value of the Risk of Ovarian Malignancy Algorithm (ROMA) index in the detection of ovarian cancer in postmenopausal women: a systematic review and meta-analysis 2025 (systematic review and meta-analysis) – Clinical Utility and Diagnostic Accuracy of ROMA, RMI, ADNEX, HE4, and CA125 in the Prediction of Malignancy in Adnexal Masses 2024 (comparative study) – Comparative Meta-Analysis of Carbohydrate Antigen 125 (CA125), Human Epididymis Protein 4 (HE4), and Diagnostic Indices (Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA)) for Pre-operative Detection of Ovarian Carcinoma 2025 (meta-analysis) – Comparison of HE4, CA125, ROMA and CPH-I for Preoperative Assessment of Adnexal Tumors 2022 (diagnostic study) – ROMA – Overview: ROMA Score (Ovarian Malignancy Risk Algorithm), Serum 2026 (laboratory reference)
Disclaimer
This article is for general education and does not diagnose ovarian cancer or determine whether an adnexal mass requires surgery. ROMA formulas, score formats, and cutoffs are assay-specific, and kidney function or benign conditions can affect CA-125 and HE4. A ROMA result should be interpreted with pelvic imaging and clinical findings by a qualified clinician, with gynecologic oncology referral when malignancy risk is significant.
