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Familial Ovarian Cancer Screening

South East of Scotland Clinical Genetic Services, Western General Hospital, Edinburgh, United Kingdom

D. Gareth Evans

Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Manchester, United Kingdom

Gabriella Pichert

Wessex Clinical Genetic Services, Princess Anne Hospital, Southampton, United Kingdom

Michael Steel

University of St Andrews, St Andrews, United Kingdom

To the Editor:

We appreciate the comments of Dr Jacobs¹ in his editorial concerning our recent article,² and agree that well-designed, rigorously conducted, and properly funded prospective trials of ovarian cancer screening among women at high risk are essential to inform screening protocols. It should be noted that Dr Jacobs is a principal investigator on two such trials: UKTOCSS (United Kingdom Collaborative Trial of Ovarian Cancer Screening), as mentioned in his editorial, and a familial screening study utilizing the same observational approach as ourselves (the United Kingdom Familial Ovarian Cancer Screening Study [UKFOCSS], which uses CA125 and transvaginal ultrasound.) Indeed the three centers whose data we reported support and are among the top five recruiting centers for UKFOCSS.

However, we would like to take this opportunity to correct and clarify some of Dr Jacobs's comments.¹ First, regarding his estimation of projected recruitment figures: over the 13-year period there was not a steady recruitment pattern, so projected figures cannot be based on this assumption. Initially, numbers of women seeking screening on the basis of family history were relatively low with a sharp increase in numbers around early to mid-1990s, which then peaked and fell. In addition, in our experience, many women also opt out of screening. In recent years, we have seen increasing numbers of women opting for prophylactic surgery in preference to screening, particularly if they have experienced equivocal results in screening. During the course of our study, the screening interval was consistent at 12 months, and the vast majority of patients had transvaginal ultrasound.

Dr Jacobs suggests that our reported low numbers of interventions for benign disease on the basis of raised CA125 levels indicates a reluctance to intervene on the basis of raised CA125 alone and that this may also have contributed to the late-stage distribution of the screen-detected cancers. Few gynecologists would intervene on the basis of one raised level of CA125. It is standard practice to establish a pattern of rising CA125 levels by repeating raised results after a 6 to 8 week period in the absence of other clinical indications for intervention. In fact, this is also the protocol for the UKFOCSS study, so Dr Jacob's comments are somewhat surprising. There has been some confusion over the interpretation of Table 5 of our article,² which lists the details of screen-detected cancers. If only one CA125 was listed on this table Dr Jacobs assumes that the CA125 is a prevalent CA125 screen. This was not the case; these were the abnormal annual results, and the previous year's normal result is not listed. These women were referred directly for gynecologic opinion rather than waiting for confirmatory repeats therefore minimizing the time between screen result and surgical intervention. Two of the women with serial results (patients 1 and 3) had repeat CA125 results to establish a rising pattern. Notably the first CA125 level in patient 3 was actually within normal limits (< 35 units/mL), however her previous estimations indicated this was a rise from her normal (previous CA125 levels for this patient were < 15 units/mL). Patient 4 has two CA125 results listed, one is her raised annual CA125 at 113 units/mL and the second a preoperative result which shows a marginal fall at 109 units/mL. Dr Jacobs suggests that the application of algorithms such as the risk of ovarian cancer algorithm may be useful in aiding interpretation of CA125 and ultrasound results, however, this algorithm does not include family history as a predictive factor and is therefore of limited utility in our patient group.

The results of our study undoubtedly raise issues about the efficacy of current screening protocols, particularly with regard to the efficacy of transvaginal ultrasound. Despite this, as Dr Jacobs highlights, the alternative to screening—prophylactic oophorectomy—is not suitable for many women for a variety of reasons. To reiterate the conclusion of our study, "Given our findings that most ovarian cancers in women at high genetic risk have elevated CA125 at presentation but that they can present at a relatively advanced stage within twelve months of a negative screen, there is a case for evaluating surveillance (within observational studies) by more frequent CA125 measurement in women who choose not to have their ovaries removed." Women must be aware of the limitations of screening so that the decisions they make are fully informed and they do not embark on screening with unwarranted confidence.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Jacobs I: Screening for familial ovarian cancer: The need for well-designed prospective studies. J Clin Oncol 23:5443-5445, 2005[Free Full Text]

2. Stirling D, Evans DG, Pichert G, et al: 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. J Clin Oncol 23:5588-5596, 2005[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stirling, D. Articles by Steel, M. Search for Related Content PubMed PubMed Citation Articles by Stirling, D. Articles by Steel, M. Social Bookmarking                            What's this?