Testing of tumour samples for mutations in the BRCA1 and BRCA2 genes using a customised next generation sequencing assay is available for all appropriate patients with castration resistant metastaticprostate cancer, in line with the requirements of the NHSE National Genomic Test Directory for Cancer v7.2, published on 8th June 2023.

Clinical Indication Name Test Code Test Name Target Gene(s) [essential] Test Scope
Prostate cancer – Adult M218.1 Multi-target NGS panel – small variant (BRCA1, BRCA2) for somatic/tissue testing BRCA1, BRCA2 Small variant detection

Patients who are eligible for NICE approved PARP inhibitor and have a diagnosis of metastatic castration-resistant prostate cancer are eligible for tumour BRCA testing. Guidelines for testing eligibility have been generated by the NEY GLH leadership team with the advice of the NEY GLH DDR sub-group. All those who wish to provide input into the future development of the service are welcome to join the NEY GLH prostate cancer working group (abbreviated to DDR [DNA Damage Response] working group), with meetings held every 2 -3 months by TEAMS.

Please contact Paula Kew or your local genomics laboratory to register interest.

In order to improve success rates and to achieve more reliable results, the NEY GLH prostate cancer clinical group have agreed strict criteria for sample conditions for testing:

  • Samples must be less than 5 years old
  • Tumour sample content should be >20%. Please send curls (not sections) – send two tubes (Eppendorf or Universal): each containing 5-10 x 10μm FFPE curls. Please note that glass slide-mounted sections at least in the first instance will not be accepted for testing
  • Bone biopsies should only be sent if they meet the above criteria and have been decalcified in a genome friendly manner, using EDTA and not pre-treated with formic acid

Sample preparation is done in the local Cellular Pathology lab under standardised molecular laboratory protocols which includes a clean molecular microtome and histopathologist training/quality assurance in preparing and assessing specimens for molecular testing  However, if your local Cellular Pathology lab is unable to undertake this type of preparation, it would need to make contractual arrangements with another Cellular Pathology lab in order to provide appropriate material to the NEY GLH for genomic testing.

If a suitable sample is not available, re-biopsy is to be considered rather than germline testing, as the latter will only detect around 20% of the total number of patients who have a BRCA mutation (and won’t detect those who have a tumour only BRCA mutation).

As testing and reporting may be carried out at any one of the three genetic laboratories within the GLH, please send samples to your local NEY GLH genetics laboratory. They will direct the testing and reporting as appropriate so that they can act as your single point of call for any queries within the GLH. Costs from that point, including transport and test costs, are commissioned and paid for by NHSE directly to the GLH, so do not need to be paid for by the referring cellular pathology lab.

Please use the NEY GLH Solid Cancer Genomics Referral form. Please ensure that the form:

  • Includes email addresses for your Cellular Pathology secretaries and pathologist;
  • Clearly specifies which tests are needed;
  • Clearly specifies tumour cell nuclei as a percent of nucleated cells.
  1. Germline testing is recommended in men under 50 with prostate cancer or under 60 with metastatic prostate cancer, or those with a significant family history with ovarian or breast cancer. See page 225 of the NHSE Rare and Inherited Disease eligibility criteria for germline BRCA testing and test ID R444.2 in the NHSE Rare and Inherited Disease National Genomic Test directory.
  2. Patients where a tumour has been found to have a BRCA mutation present should then be consented to undergo germline testing ordered by the referring oncologist or surgeon – using the referral form for germline testing. Only if they are found to have germline BRCA mutations or if they meet the criteria outlined above should they be referred to cancer genetic services for further counselling and family testing.
  3. Please note that for patients not in 1. or 2. above, germline analysis (R444.2) should only be performed as an alternative to tumour testing when there is insufficient tissue, or where the tumour testing has failed.

For any germline testing, a minimum of 3ml of blood in EDTA is required.

Reports will be emailed to the referring cellular pathology email address for integration into the full histopathology report and should not be acted upon out of context of those finding. Reference to eligibility for PARP inhibitor therapy according to BRCA status will be made in the reports.

Where a tumour BRCA mutation is identified, the report will state the need to obtain a blood sample (minimum 3ml of blood in EDTA) to establish if this is a germline or acquired (somatic) mutation. Note will be made that if present in the germline, this individual would be at increased risk of developing further BRCA-related cancers, and that other family members may also have inherited this variant.

Efforts will initially be made to achieve a TAT of 21 days, but is likely to be longer in the first instance.