ROMA Index: Ovarian Cancer Risk Assessment

What Is the ROMA Index?

The Risk of Ovarian Malignancy Algorithm (ROMA) Index is a blood test that combines two tumour markers—CA-125 and HE4—along with a woman’s menopausal status to estimate the likelihood that an ovarian mass is malignant. Unlike a standalone CA-125, the ROMA Index provides a more nuanced risk stratification, especially for premenopausal women where CA-125 alone can be falsely elevated by benign conditions such as endometriosis or fibroids.

In my clinical practice, I often see women who are anxious after an incidental finding of an ovarian cyst. The ROMA Index helps us decide who needs urgent referral to a gynaecological oncologist and who can be managed conservatively. This algorithm was developed and validated in large multicentre studies and is now widely endorsed by international guidelines, including those from the National Institute for Health and Care Excellence (NICE) in the UK.

How Is the ROMA Index Calculated?

The calculation uses two separate predictive models—one for premenopausal women and one for postmenopausal women. The formula incorporates the log-transformed values of HE4 and CA-125, plus a constant that differs by menopausal status. The result is a numeric score between 0 and 100, with a predefined cutoff to classify a patient as ‘low risk’ or ‘high risk’ of epithelial ovarian cancer.

Premenopausal Equation

ROMA score = exp(PI) / (1 + exp(PI)) × 100, where PI = –12.0 + 2.38 × ln(HE4) + 0.0626 × ln(CA-125).

Postmenopausal Equation

PI = –8.09 + 1.04 × ln(HE4) + 0.732 × ln(CA-125).

Your doctor or laboratory will run this calculation automatically once the two marker levels are measured. The LOINC code for the ROMA Index is 75699-8 (Risk of Ovarian Malignancy Algorithm [ROMA] in Serum or Plasma).

Reference Ranges and Interpretation

The ROMA Index is interpreted using validated cutoffs that depend on menopausal status. A score below the cutoff suggests low probability of malignancy; a score at or above the cutoff suggests high risk and warrants further investigation.

These thresholds are derived from the original ROMA validation study by Moore et al. (2009). It is important to note that the ROMA Index is not a diagnostic test; it only refines risk. A high score does not mean you have cancer—it means you need further evaluation, typically with imaging (e.g., transvaginal ultrasound) and possibly biopsy.

What Is the ROMA Index Used For?

The primary purpose is to triage women with a pelvic mass. The test helps differentiate benign ovarian cysts from malignant tumours, especially in settings where ultrasound findings are ambiguous. Studies show that the ROMA Index has a sensitivity of approximately 92% and specificity of 76% for detecting epithelial ovarian cancer.

ROMA Index vs CA-125

CA-125 alone is notorious for false positives in premenopausal women—conditions like endometriosis, pregnancy, uterine fibroids, and pelvic inflammatory disease can raise it. HE4 is more specific for ovarian cancer and is less affected by those benign causes. By combining them, the ROMA Index improves specificity without sacrificing sensitivity. In many guidelines, a ROMA Index is preferred over standalone CA-125 when evaluating suspicious adnexal masses.

ROMA Index During Pregnancy

Pregnancy can elevate CA-125 levels, especially in the first trimester, while HE4 remains relatively stable. The ROMA Index has not been extensively validated in pregnant women, so it should be used cautiously. If an adnexal mass is found during pregnancy, a multidisciplinary approach involving obstetrics and gynaecologic oncology is essential. The ROMA Index may still offer directional guidance, but it should not replace ultrasound or clinical judgment.

Limitations and False Positives

No test is perfect. The ROMA Index can give a false-positive result in women with benign ovarian tumours, endometriomas, or even chronic kidney disease (which elevates HE4). Conversely, false negatives can occur with mucinous ovarian cancers, which often produce less HE4. My patients typically find it reassuring when I explain that the ROMA Index is just one piece of the puzzle—imaging, family history, and symptoms all count.

How to Prepare for the Test

No special preparation is required for the ROMA Index blood test. You do not need to fast. However, it is important to inform your doctor if you are pregnant, have endometriosis, or have any chronic kidney condition, as these can alter the results. The test is performed on a simple blood sample drawn from a vein, and results are usually available within 24–48 hours.

When Should You Discuss the ROMA Index With Your Doctor?

If you have been diagnosed with an ovarian cyst or mass, or if you have symptoms such as bloating, pelvic pain, or feeling full quickly, ask your gynaecologist whether a ROMA Index is appropriate. It is also sometimes used in women with a strong family history of breast or ovarian cancer, though genetic testing for BRCA mutations is a separate step.