CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer

Olivier, R.I.; Lubsen-Brandsma, M.A.C.; Verhoef, Senno; Beurden, Marc van

doi:10.1016/j.ygyno.2005.08.038

Cited by 165 publications

(113 citation statements)

References 28 publications

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“…TVU and serum CA125 lack adequate sensitivity apart or together (15 -71% for TVU/CA125) (Laframboise et al, 2002;Scheuer et al, 2002;Tailor et al, 2003;Meeuwissen et al, 2005;Stirling et al, 2005;Olivier et al, 2006) and our finding of 42% for TVU/CA125 is in accordance with these findings.…”

Section: Discussionsupporting

confidence: 92%

“…With these limitations in mind, the SIRs suggest that the lead-time is very limited in the total and compliant group. In evaluating efficacy of screening, several factors hamper the comparison among various studies, (1) compliance to the intended screening procedure has not been examined in combination with efficacy, (2) generally, no distinction is made between prevalent and incident screen-detected cases, (3) the screening protocol may differ, such as the frequency of screening, the cutoff level of CA125 (15 -35 U ml À1 ) (Bourne et al, 1994;Jacobs et al, 1999;Kauff et al, 2005;Meeuwissen et al, 2005;Olivier et al, 2006), and the combined or sequential order of applying the screening tools (Jacobs et al, 1999;Scheuer et al, 2002;Meeuwissen et al, 2005;Stirling et al, 2005;Olivier et al, 2006), and (4) quality measures of screening tools, like sensitivity, are typically reported including occult tumours, while the proportion of women opting for a BP(S)O differs strongly across various countries (Wainburg and Husted, 2004). Consequently, the proportion of interval cancers detected during screening varies among studies from 5/7 ¼ 71% in the study by Liede et al (2002), 1/3 ¼ 33% in the study by Scheuer et al (2002) and 1/6 ¼ 17% in the study by Vasen et al (2005) ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

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No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

et al. 2007

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BRCA1/2 mutation carriers are offered gynaecological screening with the intention to reduce mortality by detecting ovarian cancer at an early stage. We examined compliance and efficacy of gynaecological screening in BRCA1/2 mutation carriers. In this multicentre, observational, follow-up study we examined medical record data of a consecutive series of 888 BRCA1/2 mutation carriers who started annual screening with transvaginal ultrasonography and serum CA125 between 1993 and 2005. The women were annually screened for 75% of their total period of follow-up. Compliance decreased with longer follow-up. Five of the 10 incident cancers were interval tumours, diagnosed in women with a normal screening result within 3–10 months before diagnosis. No difference in stage distribution between incident screen-detected and interval tumours was found. Eight of the 10 incident cancers were stage III/IV (80%). Cancers diagnosed in unscreened family members had a similar stage distribution (77% in stage III/IV). The observed number of cases detected during screening was not significantly higher than expected (Standardized Incidence Ratio (SIR): 1.5, 95% confidence interval: 0.7–2.8). For the subgroup that was fully compliant to annual screening, a similar SIR was found (1.6, 95% confidence interval: 0.5–3.6). Despite annual gynaecological screening, a high proportion of ovarian cancers in BRCA1/2 carriers are interval cancers and the large majority of all cancers are diagnosed in advanced stages. Therefore, it is unlikely that annual screening will reduce mortality from ovarian cancer in BRCA1/2 mutation carriers.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

et al. 2007

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“…7 Even when high-risk women are screened, the test does not provide considerable advantages 8 ; it does not detect tumors early enough to influence outcomes. 9 As a result, low sensitivity and a high rate of false-negative results of the CA125 test reduce access to transvaginal ultrasonography; on the other hand, the low sensitivity of transvaginal ultrasonography for early cancer suggests that the effect on prognosis would be negligible. 9 To improve detection, combinations of CA125 with other antigens have been suggested.…”

mentioning

confidence: 99%

“…9 As a result, low sensitivity and a high rate of false-negative results of the CA125 test reduce access to transvaginal ultrasonography; on the other hand, the low sensitivity of transvaginal ultrasonography for early cancer suggests that the effect on prognosis would be negligible. 9 To improve detection, combinations of CA125 with other antigens have been suggested. 10 The paradigm involves combinations of blood-based markers as the first line followed by confirmatory transvaginal ultrasonography.…”

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confidence: 99%

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

Melnikov

Scholtens

Godwin

et al. 2009

The Journal of Molecular Diagnostics

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An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n ‫؍‬ 30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n ‫؍‬ 33) and healthy controls (n ‫؍‬ 33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified , fivefold cross-validation protocol. In plasma , five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy. Despite its relatively low prevalence, 1 ovarian cancer is the most frequent cause of death from gynecological malignancies. At early stages, women are mostly asymptomatic or present with vague and non-specific symptoms, so early ovarian cancer is difficult to diagnose. Considering that patients diagnosed with stage I ovarian cancer have a 5-year survival rate over 90%, early detection of ovarian cancer may reduce cancer-related mortality.It has been suggested that a screening test for ovarian cancer should have a positive predictive value of 10% or more; such that 10 women would undergo exploratory surgery to diagnose one cancer.2 The low prevalence of ovarian cancer requires that a screening test has a sensitivity of at least 75% and a specificity of at least 99.6%. 2The screening test should also be simple, inexpensive, and produce only minimal discomfort for the patient. Such a test has yet to emerge.The most widely used procedure for ovarian cancer detection and monitoring is a blood-based test for cancer antigen 125 (CA125).3,4 Its specificity for early-stage disease is high (96% to 100%), but the sensitivity is low, 5 so the test must be combined with other diagnostic techniques. A two-line screening procedure has been suggested in which candidates with high CA125 undergo follow-up transvaginal ultrasonography. 6 Unfortunately, this combination still has only a limited sensitivity because of the low sensitivity of the initial CA125 test.7 Even when high-risk women are screened, the test does not provide considerable advantages 8 ; it does not detect tumors early enough to influence outcomes.9 As a result, low sensitivity and a high rate of false-negative results of the CA125 test reduce access to transvaginal ultrasonography; on the other hand, the low sensitivity of transvaginal ultrasonography for early cancer suggests that the effect on prognosis would be negligible. 9To impro...

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Borgfeldt

Iosif

Måsbäck

2007

European Journal of Obstetrics & Gynecology and Reproductiv

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Results: During the follow-up period of median 92 months, range 11-185 months, no relapse was found in the patients with stage Ia tumors including both the borderline tumors (n=12) and the invasive well (n=9) and moderately (n=1) differentiated ovarian cancers. One patient with poorly differentiated ovarian cancer stage 1c was pregnant at 13 weeks at the primary operation.Although, unilateral oophorectomy was performed she insisted in continuing the pregnancy. At 37 weeks she had a caesarian section and the ovarian cancer was disseminated. Chemotherapy was given but she died less than a year later. No other patient received chemotherapy. In total 30 children was born by 15 patients. Prophylactic removal of the remaining ovary +/-hysterectomy was accepted only in six of the women after completing their desire to have more children. However, several of these patients do not accept the recommendation of prophylactic oophorectomy of the contra lateral ovary and hysterectomy after completion of childbearing age. Conclusions4

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CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer

Cited by 165 publications

References 28 publications

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

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

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