A systematic review of risk-reducing cancer surgery outcomes for hereditary cancer syndromes

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Abstract

Cancer predisposition genes are rare mutations that confer a high risk of cancer. For many hereditary cancer syndromes, risk reducing surgery is the single most effective strategy for preventing cancer, but it is irreversible. It has recently attracted significant media attention, following celebrity endorsement, which has led to a perceived lack of ill-effect and guaranteed successful outcome by the general public. Given these high expectations for risk-reducing surgery, a systematic review was performed to evaluate the reported complications for patients undergoing risk-reducing surgery. A systematic review of MEDLINE, EMBASE, CINAHL, AMED and PubMed work was conducted using PRISMA for risk-reducing surgery in adults for cancer predisposition genes in breast, ovary, stomach, thyroid and colorectal. The main outcomes were 30-day morbidity and mortality associated with these procedures. Twenty-five studies (2366 patients) reporting on outcomes following risk-reducing surgery were analysed, 5 related to breast and/or ovary, 3 for stomach, 2 for thyroid and the remaining 15 were colorectal. Risk-reducing surgery was uniformly associated with 30-day morbidity, particularly for breast (variable rates), colorectal (311/1400 patients (22%)) and stomach (35/75 patients (47%)) surgery. The 30-day morbidity for ovarian risk-reducing surgery was relatively low (11/244 patients (5%)). There was also a small mortality risk associated with colorectal (1/1400 patients) and stomach (1/75 patients). This study provides an important and necessary summary of the current data, enabling clinicians to better inform patients of the associated short and long-term outcomes in risk-reducing surgery for cancer predisposition genes.

Introduction

Risk-reducing surgery has recently received significant media attention and gained public interest. In 2013, the New York Times published an editorial by Angelina Jolie outlining her own personal experience of risk-reducing surgery for BRCA 1 mutation [1]. Many experts and advocates widely applauded this disclosure, with the aim to benefit other women with strong family histories of breast cancer to get genetic tests [2]. However, others expressed concerns that this could be misinterpreted, fuelling a trend towards preventative surgery that is not medically necessary [2].

Next generation sequencing techniques allow for analysis of many different genes simultaneously, resulting in increased speed, access and lower costs of testing for hereditary cancer syndromes. As a result, and the increased public profile, an increasing number of patients are seeking genetic counselling and undergoing germline mutational testing. Patients with hereditary cancer syndromes may choose several strategies for cancer risk reduction including surgery.

Cancer predisposition genes are rare mutations that confer a high risk of cancer [3] and for many hereditary cancer syndromes, risk-reducing surgery is the single most effective strategy for preventing cancer. This strategy exists for breast (BRCA1&2) [4,5], colon (APC) [[6], [7], [8]], ovary (BRCA1&2) [9], stomach (CDH-1) [10] and thyroid (RET) [6], which all have key cancer predisposition genes [3] and provide an opportunity for risk-reducing surgery. However, risk-reducing surgery is neither feasible nor practical for some hereditary cancer syndromes. For example, patients with PTEN hamartoma tumour syndrome have an estimated 34% lifetime risk of renal malignancy, but a bilateral nephrectomy is an impractical option [11]. This review therefore focuses on hereditary cancer syndromes with feasible risk-reducing surgery options.

An editorial by Professor Brennan emphasises some key issues surrounding risk-reducing surgery for hereditary cancer syndromes such as Familial Adenomatous Polyposis [12]. This highlights the sad reality that many societies have been seduced into believing that living is risk free and demands compensation when accidents, complications and errors occur, even in the absence of malfeasance, summarised as a minatory experience [12]. Professor Brennan further concludes that in an age where technical aspects of operations are sometimes denigrated, a scenario now exists in which technical perfection is to be the norm and society will expect an operative mortality of zero [12]. However, this is a figure that is never uniformly achievable. Given these high expectations for risk-reducing surgery, we sought to systematically review the reported complications for patients undergoing this type of surgery.

Section snippets

Search strategy

A systematic review of published work was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for the conduct of a review study [13]. The study team developed a concept table and built a search strategy with a medical librarian to identify articles reporting outcomes from risk-reducing cancer surgery. Two concepts were developed: cancer genes and types of surgery. Exploded medical subject heading (MeSH) terms were combined with text word

Search results

Thirty-four thousand and eighty-nine studies were identified from the literature search of the electronic databases, which, following screening (inclusion/exclusion criteria and removal of duplicates), resulted in 25 full articles for inclusion in this qualitative synthesis (Fig. 1). Among the excluded studies, three were excluded because of duplication of reported outcomes of interest in other publications from the same institution [[15], [16], [17]]. All studies were assessed using the

Discussion

This review highlights the importance of an individualised discussion for patients with cancer predisposition genes considering risk-reducing surgery. Despite the reported outcomes being from many high-volume centres, the morbidity and mortality associated with certain risk-reducing surgery for cancer predisposition genes remains significant. Whilst previously published studies have demonstrated patients are satisfied with the cancer risk reduction, their satisfaction with the surgical outcome

Conflict of interest and source of funding

None.

No sources of support

Short running head: There are high expectations for risk-reducing surgery. A systematic review was performed to evaluate the reported complications for patients undergoing risk-reducing surgery. This study provides an important and necessary summary of the current data, enabling clinicians to better inform patients of the associated short and long-term outcomes in risk-reducing surgery for cancer predisposition genes.

Disclosures

Nil.

Acknowledgements

Nil.

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