HMN 2026: What is the Best diagnostic test for ovarian cancer in premenopausal women

Premenopausal women would benefit from a significantly more accurate diagnostic pathway for ovarian cancer, as a new study finds that an advanced ultrasound test, IOTA ADNEX, identified 9 out of 10 cancers in women who took part. Published in the BMJ, a team led by Professor Sudha Sundar—who conducted the ROCkeTS (Refining Ovarian Cancer Test Accuracy Scores) study—recommends replacing the current NHS triage test, the Risk of Malignancy Index (RMI), because it has low sensitivity for detecting cancer. Researchers found that in younger women, who haven’t been through the menopause, the RMI missed more than half of the cancers.

The new study suggested that the IOTA ADNEX ultrasound model offers far higher sensitivity, but slightly lower specificity: while this may lead to more women undergoing additional tests to exclude cancer, it represents a significantly more effective approach for detecting cancer earlier and improving patient outcomes.

The IOTA ADNEX ultrasound tests picked up 9 out of 10 women with cancer. The ultrasound tests did have lower specificity, so more women would be considered as being at risk of cancer when they did not have the disease. However, the authors suggested that when using this in the NHS, this could be reduced by using the IOTA ADNEX two-step ultrasound strategy, which uses ultrasound to first classify ovarian tumors as clearly benign (needing no further testing), then applies the ADNEX risk calculation model to all other ovarian tumors.

The study was led by Professor Sudha Sundar from the University of Birmingham. The research team recruited 1,211 women from 23 UK hospitals between 2015 and 2023 who presented with symptoms and abnormal CA125 or ultrasound findings.

The team collected data on whether participants underwent surgery or a biopsy within 3 months of joining the study, to find out if newer tests—such as the IOTA ADNEX ultrasound—might work better and understand how much these different tests cost the NHS.

Researchers evaluated six tests, including the current RMI model, ROMA (Risk of Malignancy Algorithm), the CA125 blood biomarker alone, and three ultrasound-based models developed by the International Ovarian Tumor Analysis (IOTA) group. Importantly, ultrasound was delivered mainly by NHS sonographers who had received IOTA training, certification and quality assurance.

Professor Sudha Sundar, Professor of Gynecological Cancer at the University of Birmingham and Chief Investigator of the study, said, “Diagnosing ovarian cancer in premenopausal women is challenging, due to the rarity of cancer and the non-specificity of symptoms that patients may present with.

“Our findings show that the current RMI test for ovarian cancer is missing cancers in many women, particularly those who haven’t gone through the menopause, with only around 40% of cancers being caught. Using the IOTA ADNEX test will transform care by ensuring that women at high risk are referred promptly to specialist centers for surgery, while those at a lower risk can avoid unnecessary surgery to remove their ovaries.”

Key findings include:

• The IOTA ADNEX model, applied at a 10% risk threshold, achieved 89.1% sensitivity with a specificity of 75.1%, outperforming all other tests.
• RMI at the recommended threshold of 250 demonstrated a sensitivity of only 42.6%, despite a high specificity of 96.5%, meaning it missed more than half of ovarian cancer cases.
• ROMA and IOTA SRRisk also improved sensitivity compared to RMI, but less than IOTA ADNEX.
• Most cancers detected were early stage (FIGO I/II), highlighting the potential for improved survival rates if accurate triage is implemented.
• In the ROCkeTS trial, NHS sonographers were given specific training and quality assurance so they could use the IOTA ADNEX ultrasound test—this means that the test can be rolled out across the NHS (as it doesn’t need specialists to conduct the scans)
• The team have recently shown that using the IOTA ADNEX two-step ultrasound strategy which identifies tumors which are benign offers the best balance of costs and consequences for the NHS

Professor Jon Deeks, a co-author of the study, said, “We designed this study to be as rigorous and realistic as possible. By recruiting over 1,000 premenopausal women from across the UK, testing multiple diagnostic tools side?by?side, and confirming diagnoses through surgery or biopsy or 12-months follow-up, we were able to see clearly which tests truly perform best in everyday clinical practice.”

Current diagnostic pathways rely on CA125 blood biomarker testing and ultrasound in primary care, followed by the RMI in secondary care to determine referral to specialist cancer centers. However, RMI performs poorly in younger women due to lower rates of sensitivity, which can lead to a significant proportion of cancer diagnoses being missed.

Case study: Diagnosis gave ‘peace of mind’ over treatment and recovery

Yvette Beard, a 48-year-old woman from the West Midlands, was referred to the General Gynecological team at the Sandwell and West Birmingham Hospitals NHS Trust after an ovarian cyst was found in her pelvis. To further investigate the mass, Yvette underwent a pelvic ultrasound using the IOTA-ADNEX model, which found that it was highly likely to be benign.

Following her scan, Yvette was able to discuss and choose her preferred treatment options with her doctor: the histology report from her subsequent surgery then confirmed that the mass was a benign cyst. Undergoing an ultrasound using IOTA-ADNEX not only alleviated Yvette’s anxiety and concerns prior to diagnosis but also meant that there was no delay in accessing treatment.

She said, “Following my initial symptoms, I’m grateful that I was able to get an accurate and timely diagnosis from my doctor, which gave me peace of mind about both my treatment and recovery timelines. I hope that other women across the country, who are also going through the same experience, can benefit from this new approach in the near future.”

Improving patient experiences and outcomes

As part of the study, researchers also incorporated patient advocates from Target Ovarian Cancer to ensure the research addressed real-world concerns. Anxiety among women who are referred through urgent cancer pathways remains high, even after a benign diagnosis. Therefore, improving diagnostic accuracy and triaging can help to reduce the psychological impact upon patients, as well as treating physical symptoms.

Catherine Hart, Chief Executive at Target Ovarian Cancer, said, “Ovarian cancer is notoriously difficult to diagnose, particularly in premenopausal women, as key symptoms such as abdominal bloating, pelvic pain, and urinary urgency are common and often overlap with benign conditions.”

Professor Sudha Sundar said, “An exciting area of future research is developing computer programs using artificial intelligence to help with ultrasound scans. As well as increasing diagnostic accuracy, these tools could also help reduce the long waiting times for ultrasound tests.

“The challenge now is to roll out the IOTA ADNEX across the NHS. This means training sonographers and systems to check the quality of their work regularly and making sure that doctors know how to interpret the results of the scan accurately. While this will take time and investment to implement properly, it could make a real difference to women’s lives by finding cancer earlier when it’s easier to treat.”

This paper follows on from the ROCkeTS study results in postmenopausal patients, published in The Lancet Oncology in 2024, presented a comprehensive evaluation of risk-prediction models in postmenopausal patients with suspected ovarian cancer. This multicenter, prospective diagnostic accuracy study included 1,242 postmenopausal patients recruited from 23 UK hospitals and concluded that the IOTA ADNEX ultrasound test was the most sensitive test to detect ovarian cancer.

ROCkeTS is the first prospective, multicenter, head-to-head comparison of commonly used risk prediction models for both premenopausal and postmenopausal women in primary care and secondary care.

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