Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer

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Abstract

Objective

Women at high risk of ovarian cancer are currently offered two options: either surveillance or prophylactic bilateral salpingo-oophorectomy. The efficacy and outcome of surveillance remain unclear.

Methods

We performed a retrospective study. Between 1994 and 2000, we screened 383 high-risk women, of which 152 were BRCA1/2 mutation carriers. Surveillance consisted of annual gynecological examination, transvaginal ultrasound, and serum CA125 measurement. Exploratory or prophylactic surgery was performed in selected cases.

Results

There were no screen-detected primary ovarian cancers. Abnormal results at surveillance were observed in 74 (19.3%) of women; in 47 (63.5%), the abnormalities disappeared spontaneously. Exploratory surgery was performed in 20 (27.0%) women in whom one malignancy was found (metastatic breast cancer in the ovary). A rising CA125 value prompted further (non-surgical) evaluation in three women with a history of breast cancer: recurrent breast cancer was diagnosed in two women; in the third, a chondrosarcoma was found. 133 women opted for prophylactic bilateral salpingo-oophorectomy, whereby two unexpected malignancies were found (fallopian tube cancer and metastatic breast cancer). One interval primary ovarian cancer occurred, presenting as papillary serous carcinoma of the peritoneum 14 months after prophylactic bilateral salpingo-oophorectomy. Complications of prophylactic surgery were encountered in 15 (11.5%) women.

Conclusions

Ovarian cancer surveillance has limited sensitivity, and a high number of false positive findings. This can lead to unnecessary surgical interventions, possibly resulting in surgery-related complications. It is important to inform high-risk women of these limitations. For now, prophylactic bilateral salpingo-oophorectomy remains the optimal risk-reducing strategy for women at high risk.

Introduction

It is estimated that 5% of all cases of ovarian cancer are caused by hereditary factors. BRCA1/2 mutation carriers have a highly increased risk of breast and ovarian cancer. The cumulative lifetime risk of developing ovarian cancer for these women is estimated to be 13–63% [1], [2], [3], [4], [5], [6], [7], [8]. Family cancer clinics have been instituted worldwide to provide counseling, genetic testing, surveillance programs, and prophylactic surgery, aiming at early detection or prevention of ovarian (and breast) cancer in these high-risk women. Surveillance protocols for ovarian cancer vary between clinics, but at minimum consist of transvaginal ultrasound and CA125 measurements. Many reports on the efficacy of surveillance for ovarian cancer have been published [9], [10], [11], [12], [13], [14], [15], [16]. However, it remains unclear whether surveillance results in a reduction of the mortality and/or morbidity rate of ovarian cancer. Moreover, negative effects such as unnecessary surgical intervention and related complications are rarely taken into account. In this report, we describe the first results of the surveillance program for ovarian cancer in high-risk women, as performed between 1994 and 2000 at the family cancer clinic of our institution. The outcome of the surveillance program for breast cancer in this population has been reported elsewhere [17], [18], [19].

Section snippets

Patient selection and counseling

In a historic cohort study, we analyzed the data from all women at high risk of ovarian cancer due to a genetic predisposition or family history, who were screened at the Rotterdam Family Cancer Clinic, from January 1, 1994 until December 31, 2000. All women with a personal history of ovarian cancer were excluded. All participants were members from hereditary breast and/or ovarian cancer families [HB(O)C], as defined by the criteria shown in Table 1. Women were counseled with regard to their

Population characteristics

A total of 383 women was included, of whom the main characteristics are shown in Table 2. There were 127 BRCA1 and 25 BRCA2 mutation carriers (39.7%). 306 (80%) women were premenopausal. During the study period, a total of 1273 surveillance visits was made, with a mean of 2.6 visits per women. Only 8 women entered the surveillance program after PBSO; all other women had at least 1 screening visit before an eventual PBSO. In 11 women, surveillance started before 30 years, due to various reasons.

Discussion

Although the population we screened is at high risk for ovarian cancer, as indicated by the high percentage (39.7%) of BRCA1/2 mutation carriers, we only found one primary ovarian cancer that was not screen detected. This is a low yield, compared to the incidence of 32 per 1000 PY (95% C.I. 9–55 per 1000 PY), as reported by Scheuer et al. [16]. Most likely this can be explained by the age difference of the 2 populations studied (mean age in our study: 40.0 years, in the Scheuer study: 47.7

Acknowledgment

The authors would like to thank Ms. E. Crepin for her help with the collection of the data.

References (54)

  • M.G. Muto et al.

    Screening for ovarian cancer: the preliminary experience of a familial ovarian cancer center

    Gynecol. Oncol.

    (1993)
  • P.D. De Priest et al.

    A morphology index based on sonographic findings in ovarian cancer

    Gynecol. Oncol.

    (1993)
  • A. Kurjak et al.

    Three-dimensional ultrasound and power doppler improve the diagnosis of ovarian lesions

    Gynecol. Oncol.

    (2000)
  • S.A. Narod et al.

    Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study

    Lancet

    (2001)
  • A.C. Ansink et al.

    Occult cancer in the fallopian tube in patients with a BRCA-1 germline mutation

    Gynecol. Oncol.

    (2001)
  • P.G. Rose et al.

    Germline BRCA2 mutation in a patient with fallopian tube carcinoma: a case report

    Gynecol. Oncol.

    (2000)
  • R.P. Zweemer et al.

    Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations

    Gynecol. Oncol.

    (2000)
  • P.J. Paley et al.

    Occult cancer of the fallopian tube in BRCA-1 germline mutation carriers at prophylactic oophorectomy: a case for recommending hysterectomy at surgical prophylaxis

    Gynecol. Oncol.

    (2001)
  • M.N. Hebert-Blouin et al.

    Fallopian tube cancer in a BRCA1 mutation carrier: rapid development and failure of screening

    Am. J. Obstet. Gynecol.

    (2002)
  • D.A. Levine et al.

    Risk of endometrial carcinoma associated with BRCA mutation

    Gynecol. Oncol.

    (2001)
  • O. Lavie et al.

    BRCA1 germline mutations in women with uterine serous papillary carcinoma

    Obstet. Gynecol.

    (2000)
  • J.P. Struewing et al.

    The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews

    N. Engl. J. Med.

    (1997)
  • A.S. Whittemore et al.

    Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer

    Am. J. Hum. Genet.

    (1997)
  • M.S. Brose et al.

    Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program

    J. Natl. Cancer Inst.

    (2002)
  • D.F. Easton et al.

    Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast cancer linkage consortium

    Am. J. Hum. Genet.

    (1995)
  • Cancer risks in BRCA2 mutation carriers

    J. Natl. Cancer Inst.

    (1999)
  • R. Bell et al.

    The performance of screening tests for ovarian cancer: results of a systematic review

    Br. J. Obstet. Gynaecol.

    (1998)
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