Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System

Stirling, David; Evans, D. Gareth; Pichert, Gabriella; Shenton, Andrew; Kirk, Elaine N.; Rimmer, S.; Steel, C. M.; Lawson, Sheila; Busby-Earle, R. M. C.; Walker, Jane; Lalloo, Fiona; Eccles, Diana; Lucassen, Anneke; Porteous, Mary

doi:10.1200/jco.2005.05.097

Cited by 147 publications

(89 citation statements)

References 29 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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“…This complicates comparisons between the different groups. See Table 6 for an overview of the most recent surveillance studies of high-risk women (TVU, CA-125 with (Dorum et al, 1999;Meeuwissen et al, 2005;Vasen et al, 2005) or without pelvic examination Laframboise et al, 2002;Scheuer et al, 2002;Stirling et al, 2005). Some studies report detection of advanced stage ovarian cancer, while a disappointing low number of patients appeared to have early stage cancer.…”

Section: Discussionmentioning

confidence: 99%

Surveillance of women at high risk for hereditary ovarian cancer is inefficient

et al. 2006

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To determine the effectiveness of annual gynaecological screening (pelvic examination, transvaginal ultrasound, and CA-125), a prospective cohort study of women at high risk for hereditary ovarian cancer was conducted. Women were offered DNA analysis followed by either annual screening or prophylactic bilateral salpingo-oophorectomy (BSO). Study population consisted of 512 highrisk women (median follow-up 2.07 years, range 0 -9.4 years): 265 women (52%) had a BRCA mutation. Persisting abnormalities indicated diagnostic surgery in 24 women resulting in one primary ovarian cancer FIGO stage IIIc was found. The effectiveness of screening was studied by calculating the probability of finding ovarian cancers in the BRCA-1 and BRCA-2 carrier group and comparing this to the identified number of ovarian cancers. The number of ovarian cancer patients found at surveillance was in accordance with the predicted number of ovarian cancers. A total number of 169 women underwent prophylactic BSO: one ovarian cancer stage IIb was found. In conclusion, the surveillance programme for hereditary ovarian cancer does identify patients with ovarian cancer but is very inefficient considering the high number of surveillance visits and the advanced stage of ovarian cancer in the identified patient. For prevention of advanced stage ovarian cancer, prophylactic BSO from age 35 -40 years is a more efficient alternative.

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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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Screening for Familial Ovarian Cancer: Failure of Current Protocols to Detect Ovarian Cancer at an Early Stage According to the International Federation of Gynecology and Obstetrics System

Cited by 147 publications

References 29 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

Surveillance of women at high risk for hereditary ovarian cancer is inefficient

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

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