Psychological outcomes of familial ovarian cancer screening: No evidence of long-term harm☆
Highlights
► Abnormal results of familial ovarian cancer screening may raise women's concerns in the short-term but not in the longer-term. ► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy. ► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
Introduction
Ovarian cancer is one of the leading causes of cancer death in women in the UK and US [1], [2]. Diagnosis of early stage ovarian cancer is associated with improved survival rates compared with late stage disease, hence the expectation that screening for early disease may reduce mortality. Approximately 10% of women who develop ovarian cancer have a strong family history of breast and/or ovarian cancer. In some of these families a BRCA1 or BRCA2 gene mutation can be identified, which is associated with a 25–45% lifetime risk of developing ovarian cancer [3]. Despite clear evidence that risk-reducing salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian, fallopian tube and breast cancer [4], [5], [6], it is not the choice of all women mainly due to loss of fertility and quality of life issues associated with the onset of early menopause [7]. Early detection or prevention strategies such as ovarian cancer screening (OCS) are still being investigated and are not recommended outside clinical trials. In response to the growing literature of lack of efficacy of annual OCS in these high-risk women, the UK Familial Ovarian Cancer Screening Study was established to determine the effectiveness of an annual serum CA125 test and transvaginal ultrasound scan (UKFOCSS Phase 1) [8] and more recently, 4-monthly CA125 tests combined with annual transvaginal ultrasound scans (UKFOCSS Phase 2, 2007–2011).
Evidence regarding the psychological as well as clinical outcomes of frequent familial OCS is essential. The combination of transvaginal ultrasound (TVS) and CA125 yields a significant rate of false positive abnormalities, particularly in pre-menopausal women [9]. This is magnified by use of the Risk of Ovarian Cancer (ROC) algorithm [10] that recalls 15% of women with the highest risk based on change in CA125 levels from individual baseline. Population breast screening studies suggest that women who have to undergo further tests following an abnormal result may experience adverse psychological consequences, even if further tests are normal [11], and may be discouraged from attending subsequent screening [12]. In familial OCS, false positive results of ovarian scans have been associated with transient increases in anxiety compared to normal results [13]. A US study of women at increased familial risk found reduced quality of life six months after receiving an abnormal (yet benign) result of combined CA125 and TVS screening [14]. Population-based studies of the impact of abnormal OCS results show mixed findings [15], [16], [17].
The longer-term psychological and behavioural consequences of increasing the frequency of OCS tests have not previously been evaluated. Cross-sectional data from the study suggested that withdrawal from screening in favour of surgery was influenced by prior experience of screening, past recall due to an abnormal result, and higher levels of cancer distress [18]. The present study reports prospective longitudinal data regarding the short- and longer-term impact of UKFOCSS Phase 2 screening on ovarian cancer-specific distress, anxiety and depression, overall reassurance, and rate of withdrawal from screening in a large sample of women at increased risk. The primary hypothesis was that women recalled for further tests due to an initial abnormal result would report higher cancer-specific distress shortly after being returned to routine screening compared with women who received a normal result. Secondary hypotheses were that initial recall would be associated with distress and a lack of reassurance in the longer-term, and would prompt withdrawal from familial OCS.
Section snippets
Participants
Women aged over 35 years and identified as at increased genetic risk (estimated lifetime risk > 10%) were recruited from those consenting to UKFOCSS Phase 2. UK FOCSS participants were recruited from women registered with the UK Familial Ovarian Cancer Registry, attending clinical genetic centres participating in UK FOCSS, or were identified in other clinics (e.g., gynaecology clinics, medical oncology clinics) as being at high risk of ovarian cancer due to their family histories. All women
Participation bias
Table 1 displays T1 scores for questionnaire completers and non-completers at each subsequent stage. Women who were sent but did not complete T2 questionnaires reported significantly higher T1 HADS-Anxiety (p ≤ .01) and T1 HADS-Depression (p ≤ .01), and were significantly more likely to have had an abnormal result (p ≤ .001), than T2 completers. Within the recall group, there were no significant T1 differences between women who were sent but did/did not complete the T3 questionnaire. T4
Discussion
The present study evaluated the short- and longer-term psychological consequences of frequent OCS in a large sample of women at increased risk. It revealed a small, significant short-term adverse effect, with higher cancer-specific distress in women who received an abnormal result. The effect of screening result on general anxiety and depression was not significant, suggesting that measures of cancer-specific distress such as the IES are more sensitive to subtle psychological consequences of
Conflict of interest statement
AR: Received honoraria from Fujirebio Diagnostics for lecturing on familial ovarian cancer screening. UM: Financial interest through UCL business and Abcodia Ltd in the third party exploitation of clinical trial biobanks which have been developed through research at UCL. UM also received grant funding from MRC, CRUK, NIHR, Eve Appeal and European Union for research into ovarian cancer screening and biomarkers.
Acknowledgements
A major portion of this work was done at UCLH/UCL within the Women's Health Theme of the NIHR UCLH/UCL Comprehensive Biomedical Research Centre supported by the UK Department of Health. We would like to acknowledge Louise Bayne, Rachel Iredale, Ian Jacobs, and the late Joan Austoker for their contributions to the study as members of the study management group. Invaluable administrative assistance was given by Philip Badman, Lesley Hague, Kathryn Harris, Lisa Hinton, Liza James, Tracy Pearmain,
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This work was supported by a grant from the BUPA Foundation.