Mainstreaming cancer susceptibility gene testing

As molecular biomarkers become a routine part of the diagnostic work-up for many malignancies, the clinical community is investigating the feasibility and utility of mainstreaming constitutional (germline) cancer susceptibility gene testing in patients with selected solid tumours.

The term ‘mainstreaming’, in the context of constitutional (germline) genomic testing, describes pre-test counselling and consent processes being undertaken at the point-of-care by a member of the clinical cancer team caring for the patient.

Referral to a clinical genetics professional is usually reserved for those patients found to have a pathogenic or uncertain variant, or patients with a suspected syndromic cancer predisposition or complex family histories. This mainstream approach saves time, is fiscally advantageous and, importantly, provides continuity of knowledge for both the treating clinicians and the patient.

Evidence from clinical studies

Following approval of poly-ADP ribose polymerase (PARP) inhibitors for use in patients with ovarian cancer who have a constitutional (germline) pathogenic variant in BRCA1 and BRCA2, a routine companion test of these genes became necessary to inform clinical management. Multiple studies in various healthcare settings have demonstrated that mainstreaming of constitutional genomic tests for patients with ovarian cancer is feasible, cost-effective and acceptable to clinicians and patients alike.

Mainstreaming of constitutional (germline) testing has since been expanded to include patients with other cancer types, particularly those cancer types where the test results will directly inform therapeutic decision-making.

A systematic review that addressed the feasibility of mainstreaming germline genomic testing in cancer care concluded that mainstream genomic testing for germline variants is feasible in the daily practice of cancer-care healthcare professionals. However, it highlighted the need for a structured patient pathway, formalised training procedures, and the maintenance of close collaborations between clinical genetics specialists and other clinical teams.

The authors highlighted some key elements to achieve a robust mainstreaming service:

• genomic literacy of the clinical team, enabled by bespoke education and training programmes;
• job planning to accommodate mainstreaming consulting time; and
• pathway mapping of mainstream service to include timing, return of results, and collaboration with clinical genetics.

Mainstreaming in the NHS Genomic Medicine Service

The NHS’s genetics laboratory services in England underwent a transformative reconfiguration in 2019, such that genomic testing is now centralised through seven Genomic Laboratory Hubs. Part of the reconfiguration included standardisation of genomic (constitutional and somatic) testing criteria. Criteria for such testing are now defined through the National Genomic Test Directory.

The directory also outlines which clinicians in what specialities can order such tests. In cancer care, the majority of tests can be ordered by clinicians working in appropriate specialities, as well as vocationally trained clinical geneticists and genetic counsellors.

Challenges in implementing the mainstreaming of genomic testing include:

• legal and ethical considerations;
• a lack of confidence among mainstream clinicians;
• suboptimal availability of (and access to) training of clinical teams; and
• the capacity within treating teams to absorb this additional work.

Addressing knowledge gaps

In 2015, the Association of Cancer Physicians established an oncogenetic training working party (OTWP) to identify and address any gaps in knowledge among medical oncologists in oncogenetics. This prompted the revision of the medical oncology specialist training curriculum to include greater emphasis on genomic medicine as applied to cancer care. A similar revision of the clinical oncology specialist training curriculum was also undertaken. Broadly, the proposed three levels of expertise were:

1. for all oncologists, an understanding of the availability and limitations of current technologies for stratified cancer medicine, and the distinction between somatic and constitutional (germline) variation;
2. genomics ‘champions’ who can provide additional input and advice regarding heritable susceptibility to cancer within a multidisciplinary team meeting setting; and
3. advanced training for oncologists who wish to develop specialist expertise in cancer genetics and genomics.

A wealth of educational supports – including factsheets, just-in-time resources and massive open online courses – have been developed by NHS England’s National Genomics Education programme and other groups. Furthermore, opportunities for continuous upskilling – such as national multidisciplinary team meetings, consensus meetings and ‘lunch and learn’ webinars – have been developed by organisations such as the British Society for Genetic Medicine, the UK Cancer Genetics Group and the Cancer Variant Interpretation Group UK (CanVIG UK).

The role of specialist nurses

Increasing evidence supports the sharing or transferring of counselling responsibilities from oncologists and surgeons to cancer specialist nurses. As genomics moves from niche to necessity, and with the support of the nursing and midwifery colleges who recognise the importance of genomic literacy, cancer nurse specialists are now well placed to take up mainstreaming as part of their roles.

The national Lynch transformation team (led by North Thames Genomic Medicine Service Alliance) has worked with local cancer alliances to appoint nurse specialists across the health service. This ensures a country-wide equitable rollout of mainstreaming genomic testing in patients with endometrial and colorectal cancer who are demonstrating somatic features suggestive of a potential underlying diagnosis of Lynch syndrome.

Adoption of broader mainstreaming responsibilities by clinical nurse specialists will need workforce task analysis and evolution of role descriptions to include genomic literacy in the skill set. Training needs are currently being reviewed by NHS leadership. Macmillan Cancer Support has also recently undertaken a survey review of cancer nurse specialists’ attitudes and needs related to mainstreaming of genomic testing (to include capacity and knowledge current limitations), which is due to be published in 2023.

For clinicians

• British Society for Genetic Medicine
• Cancer Genetics Group
• CanGene-CanVar
• NHS England: Accelerating genomic medicine in the NHS

For patients

• The Royal Marsden NHS Foundation Trust: Patient information library