Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study

Jacobs, Ian; Skates, Steven J.; Davies, Anthony; Woolas, Robert; Jeyerajah, Arjun R.; Weidemann, Pru; Sibley, Karen; Oram, David

doi:10.1136/bmj.313.7069.1355

Cited by 176 publications

(95 citation statements)

References 15 publications

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“…The specificity of screening with CA125 was initially improved by the use of pelvic ultrasound as a second-line test to assess ovarian volume and morphology. Using multimodal screening incorporating sequential CA125 and pelvic ultrasound, a specificity of 99.9% and PPV of 26.8% (ϳ4 operations for each cancer) for detection of ovarian and fallopian tube cancer was achieved in 22,000 postmenopausal women (63,64). With the accumulation of data in this study, ovarian morphology has been used to refine algorithms for the interpretation of ultrasound in postmenopusal women with elevated CA125 levels (65,66).…”

Section: Ovx1mentioning

confidence: 99%

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Jacobs

Menon

2004

Molecular & Cellular Proteomics

421

312

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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.

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Section: Ovx1mentioning

confidence: 99%

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Jacobs

Menon

2004

Molecular & Cellular Proteomics

421

312

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“…Although the role of CA125 in screening remains controversial, there is evidence that serum elevation is associated with an increased risk of ovarian cancer. We have previously reported that asymptomatic postmenopausal women with a CA125 ≥ 30 U ml -1 have a 36-fold increased risk of diagnosis for ovarian cancer in the subsequent year (Jacobs et al, 1996). This data was derived from a multimodal screening study which used pelvic ultrasound as a secondary test.…”

mentioning

confidence: 99%

Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation

et al. 1999

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The CA125 tumour marker has an established clinical role in monitoring the course of ovarian cancer during and after therapy (Rustin et al, 1996a(Rustin et al, , 1996b. In addition this marker is of value as a prognostic indicator (Gadducci et al, 1995;Nagele et al, 1995) and in the differential diagnosis of pelvic adnexal masses in symptomatic patients (Jacobs et al, 1990;Tingulstad et al, 1996). CA125 is also currently under investigation as a potential screening test for ovarian cancer (Jacobs et al, 1993). Although the role of CA125 in screening remains controversial, there is evidence that serum elevation is associated with an increased risk of ovarian cancer. We have previously reported that asymptomatic postmenopausal women with a CA125 ≥ 30 U ml -1 have a 36-fold increased risk of diagnosis for ovarian cancer in the subsequent year (Jacobs et al, 1996). This data was derived from a multimodal screening study which used pelvic ultrasound as a secondary test. We have now been able to perform a further analysis to quantify the value of pelvic ultrasound in refining the risk of cancer amongst asymptomatic women with CA125 elevation. METHODS DesignThe overall study design has been described in a previous report (Jacobs et al, 1988(Jacobs et al, , 1993. A total of 22 000 post-menopausal women, aged ≥ 45 years underwent serum CA125 screening. Women with a CA125 level ≥ 30 U ml -1 underwent an ultrasound. Transabdominal and/or transvaginal ultrasonography was used to measure the diameter of each ovary in three planes and to document ovarian morphology. Ovarian volume was calculated using the formula for an ovoid (Campbell et al, 1989). Ovarian morphology was classified as normal if the ovaries exhibited uniform hypoechogenicity and smooth outlines. All other morphological appearances were classified as abnormal. Women with abnormal results on scan were referred to a gynaecologist for assessment and further management. All women were followed up annually during the study by a questionnaire that specifically enquired about any illness or hospital visit in the previous year. When information suggested that a study participant may have had a gynaecological malignancy, histopathological and clinical information was obtained from the general practitioner and/or hospital. Statistical analysisIndex cancers were defined as primary invasive epithelial carcinomas of the ovary and fallopian tube (Jacobs et al, 1996). The risk of index cancer at time interval t from the date of ultrasound in volunteers with scans satisfying a particular ultrasound criterion (abnormal ovarian morphology and volume over a specified cutoff) was calculated by dividing the number of volunteers with scans satisfying that criterion who developed index cancers within time t by the total number of volunteers with scans satisfying the criterion. Cumulative risk curves were constructed by plotting the calculated risk values against time. The observed risk of index cancer for all 22 000 study volunteers as well as for all volunteers with CA125 ≥ 30 U ml...

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“…The value of tumour antigen CA 125 for the early diagnosis of ovarian cancer in premenopausal women is limited because non-malignant conditions such as endometriosis or infections are also associated with increasing serum levels of CA 125 (Jacobs and Bast, 1989;Oram and Jeyarajah, 1994). However, even in post-menopausal women, the value of serum CA 125 level for early diagnosis of ovarian cancer is under investigation because it is elevated in a significant number of patients with early-stage disease (Jacobs et al, 1996).…”

mentioning

confidence: 99%

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

Obermair

Tempfer²,

Hefler³

et al. 1998

Br J Cancer

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Summary As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml-', VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass.

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Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study

Abstract: Objective-To determine the risk of invasive epithelial ovarian cancer and fallopian tube cancer associated with a raised concentration of the tumour marker CA 125 in asymptomatic postmenopausal women.

Cited by 176 publications

References 15 publications

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation

Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer

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