Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Abstract

Ovarian cancer is characterize by few early symptoms, presentation at an advanced stage, and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. During the last decade, a research effort has been directed toward improving outcomes for ovarian cancer by screening for preclinical, early stage disease using both imaging techniques and serum markers. Numerous biomarkers have shown potential in samples from clinically diagnosed ovarian cancer patients, but few have been thoroughly assessed in preclinical disease and screening. The most thoroughly investigated biomarker in ovarian cancer screening is CA125. Prospective studies have demonstrated that both CA125 and transvaginal ultrasound can detect a significant proportion of preclinical ovarian cancers, and refinements in interpretation of results have improved sensitivity and reduced the false-positive rate of screening. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from ovarian cancer is still unclear. Prospective studies of screening are in progress in both the general population and high-risk population, including the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKC-TOCS), a randomized trial involving 200,000 postmenopausal women designed to document the impact of screening on mortality. Recent advances in technology for the study of the serum proteome offer exciting opportunities for the identification of novel biomarkers or patterns of markers that will have greater sensitivity and lead time for preclinical disease than CA125. Considerable interest and controversy has been generated by initial results utilizing surface-enhanced laser desorption/ionization (SELDI) in ovarian cancer. There are challenging issues related to the design of studies to evaluate SELDI and other proteomic technology, as well as the reproducibility, sensitivity, and specificity of this new technology. Large serum banks such as that assembled in UKCTOCS, which contain preclinical samples from patients who later developed ovarian cancer and other disorders, provide a unique resource for carefully designed studies of proteomic technology. There is a sound basis for optimism that further developments in serum proteomic analysis will provide powerful methods for screening in ovarian cancer and many other diseases.

Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)

“…Current strategies for the detection of EOC are based on biochemical markers, such as CA125, and biophysical markers assessed by ultrasound and/or Doppler imaging of the ovaries. 4,5 Unfortunately, the clinical utility of these strategies for the early detection of EOC using these modalities have been limited due to the lack of specificity and predictive value. [6][7][8] Owing to the surface epithelial origin of EOC, mucins can be interesting biomolecules to serve as markers of diagnostic significance.…”

“…16,17 Despite being a sensitive marker, the utility of CA125/MUC16 is limited owing to its elevation in benign conditions such as, endometriosis, pelvic inflammatory disease and pregnancy. 2,3,5 Another mucin, MUC1 has also been studied in relation to its aberrant expression and pathological functions in ovarian carcinoma. MUC1 is a transmembrane mucin that is overexpressed in ovarian cancer and has been shown to influence the metastatic ability of ovarian carcinoma.…”

Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer

“…Monitoring the patients with transvaginal ultrasonography and CA125 every third to six months has been proposed. However, screening by transvaginal ultrasonography and serum CA-125 measurement in women at increased risk of ovarian cancer is ineffective in detecting ovarian malignancy before spread from the ovaries and no study has showed any benefit in overall survival [29][30][31]. We recommend prophylactic oophorectomy of the contra lateral ovary and hysterectomy after completion of childbearing in patients with borderline tumors or early invasive cancer.…”

"Ovarian Neoplasms- Histopathological Patterns and Relative Frequencies in an Indian Tertiary Care Hospital"

“…[1,2] There are marked differences in distribution of different cancers in different regions of the world. [2,3] Ovarian cancer is the most frequent cause of death from gynaecological cancers and the fourth most frequent cause of death from cancer in women in Europe, United States [4] and Eastern India. [5] Exact incidence in India is not known, but ovarian cancer is the 4th most common cancer among females of India and continues to present at an advanced age.…”