Novel Approaches to Ovarian Cancer Screening

Abstract

Purpose of Review: Both conventional and novel approaches to early detection of ovarian cancer are reviewed in the context of new developments in our understanding of ovarian cancer biology.Recent Findings-While CA125 as a single value lacks adequate specificity or sensitivity for screening, large studies have shown that a 2 stage strategy which tracks CA125 change over time and prompts transvaginal ultrasound (TVS) for a small subset of women with abnormally rising biomarker values achieves adequate specificity and detects a higher fraction of early stage disease. Sensitivity could clearly be improved in both blood tests and in imaging. Metastasis can occur from ovarian cancers too small to increase blood levels of protein antigens and a significant fraction of ovarian cancers arise from the fimbriae of fallopian tubes that cannot be imaged with TVS. Autoantibodies, miRNA, ctDNA, DNA methylation in blood and cervical mucus might improve sensitivity of the initial phase and magnetic relaxometry and auto-fluorescence could improve imaging in the second phase.Summary-Enhancing the sensitivity of two stage strategies for early detection could reduce mortality from ovarian cancer.

Circulating Cell-Free DNA Methylation Profiles in the Early Detection of Ovarian Cancer: A Scoping Review of the Literature

“…Although small yields of cfDNA extractable from peripheral blood will continue to be a barrier to the validation of methylation methods, technological advancements will assist in overcoming this technical hurdle; in clinical practice, larger volume blood draws can also offset the low cfDNA yields. Until then, other techniques currently being explored include methylation analysis of bodily fluids closer to the ovaries such as endometrial lavages, endocervical brushings, Papanicolaou smears, and vaginal fluids [ 4 , 9 ].…”

“…For ovarian cancer, a minimally invasive diagnostic marker would be invaluable. However, despite ample attempts at studying biomarkers and algorithms, efforts have fallen short in identifying a reliable strategy for the detection of ovarian cancer [ 4 ]. As such, the nature and time course of DNA epigenetic alterations make methylation status a unique and robust biomarker compared to other liquid biopsies specifically for early cancer detection.…”

“…Most epithelial OCs have high-grade serous histology, an aggressive subtype with few known risk factors, the majority of which present with advanced-stage disease and have a poor prognosis. Cancer-antigen 125 (CA125), which is elevated in up to 90% of advanced-stage disease [ 4 ], remains the most commonly used marker for monitoring high-grade serous OC [ 5 , 6 ]. However, CA125 has several shortcomings including poor sensitivity for early-stage cancers and poor specificity given its elevation in many other conditions [ 7 ].…”

Repositioning Quinacrine Toward Treatment of Ovarian Cancer by Rational Combination With TRAIL

“…Cancer Facts & Figures 2019). Due to lack of an effective screening test ( 27 ), ovarian cancer typically presents at a later stage (Stage III or IV) and one third of patients have malignant ascites at initial presentation ( 28 ). Current treatment of ovarian cancer is primarily limited to surgery and chemotherapy (NCCN guidelines).…”

Frontline Management of Epithelial Ovarian Cancer—Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research

“…It is the fifth most common cause of cancer-related death in women in the United States, with an estimated 21,750 new cases and 13,940 deaths in 2020 [ 2 ]. Because of a lack of effective screening [ 3 ] and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer is primarily limited to cytoreductive surgery and systemic chemotherapy.…”