Advances in ovarian cancer screening and early detection: from biomarkers to multivariate index assays

ABSTRACT Introduction Ovarian cancer is a leading cause of cancer-related death in women, primarily due to nonspecific symptoms and diagnosis at an advanced stage. Improving outcomes through earlier diagnosis and effective population screening remains a global priority. Context Existing modalities ,including CA125 and transvaginal ultrasound (TVUS), lack sufficient specificity and sensitivity, and no screening strategy has demonstrated a reduction in mortality. Multivariate Index Assays (MIAs), that combine multiple biomarker results into a single risk score, have emerged as a promising approach for differential diagnosis of adnexal masses, early detection, and screening. Areas covered This review summarizes current literature and clinical trial data on MIAs in ovarian cancer, describing their advantages over single biomarkers, their potential to improve patient outcomes, and their role in personalized medicin. Successful clinical adoption of MIAs will depend on well-designed prospective studies that robustly validate their clinical utility. Expert opinion/commentary It is also critical to clearly distinguish between diagnostic and screening applications, as each requires different performance characteristics, regulatory pathways, and target populations, and no ovarian cancer screening test is currently approved for routine use. Plain Language Summary Ovarian cancer is one of the leading causes of cancer death in women, mainly because it is often diagnosed too late. When found early, outcomes are much better, but right now, there is no approved screening test that can save lives by reliably detecting ovarian cancer before symptoms appear. Traditional methods like CA125 blood tests and transvaginal ultrasound (TVUS) are commonly used in clinical management of symptomatic patients. They are not accurate enough on their own to guide confident decisions in diagnosing or ruling out ovarian cancer. To improve this, researchers have been developing Multivariate Index Assays (MIAs), tests that combine the results of several biomarkers into a single score to better predict cancer risk. This review looks at recent research and clinical trials exploring how MIAs could help detect ovarian cancer earlier and improve patient care. It also considers how these tests could be used in more personalized approaches to treatment and be included in international clinical guidelines in the future. While these new tools are promising, the review emphasizes the need to clearly separate the goals of diagnostic tests (used when symptoms are present) from screening tests (used in people without symptoms). No screening test for ovarian cancer has been approved so far and any future test must meet specific requirements to be used safely and effectively in clinical practice.