Risk-reducing surgery for individuals with cancer-predisposing germline pathogenic variants and no personal cancer history: a review of current UK guidelines

Abstract

Identifying healthy carriers of germline pathogenic variants in high penetrance cancer susceptibility genes offers the potential for risk-reducing surgery. The NHS England National Genomic Test Directory offers germline and somatic testing to patients with certain cancers or rare and inherited diseases, or, in some cases, to their relatives. This review summarises current UK guidelines for risk-reducing surgical interventions available for individuals with no personal history of cancer, who are determined to carry germline pathogenic variants. An electronic literature search of NICE guidelines and PubMed citable articles was performed. NICE guidelines are available for bilateral mastectomy and are currently in development for risk-reducing bilateral salpingo-oophorectomy. Guidelines developed with affiliation to, or through relevant British Surgical Societies or international consensus, are available for risk-reducing hysterectomy, polypectomy, gastrectomy, and thyroidectomy. There is a disparity in the development and distribution of national guidelines for interventions amongst tumour types. Whilst we are focusing on UK guidelines, we anticipate they will be relevant much more generally and so of interest to a wider audience including where there are no national guidelines to refer to. We suggest that, as genetic testing becomes rapidly more accessible, guideline development for interventions should be more closely aligned to those for testing.

Hereditary genetic testing and mainstreaming: a guide for surgeons

“…In any case, bringing genetic testing further upstream in the clinical timeline will inevitably require surgeons to have more involvement in (and knowledge of) the testing process than before. Its implications for risk-reducing surgery (including in unaffected relatives who are found to carry GPVs) 3 also mean that discussions around genetic status are increasingly likely to form at least part of surgeons’ consultations in future.…”

“…In addition, the importance of germline testing with regard to treatment planning is also becoming progressively apparent. Various interventions, including both risk-reducing (prophylactic) surgery 3 and, more recently, the use of poly(ADP-ribose) polymerase (PARP) inhibitors (e.g. olaparib), are influenced heavily by patients’ BRCA status.…”