Importance of genetic testing in prostate cancer

Kusha Kalideen unpacks why genetic testing helps determine prostate cancer treatment, specifically with the use of the targeted drugs, PARPi.

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Metastatic castration resistant prostate cancer (mCRPC) is an aggressive, advanced form of prostate cancer associated with poor prognosis. While treatment options are limited, a class of cancer drugs, known as poly (ADP-ribose) polymerase inhibitors (PARPi), has shown improved survival and reduced disease progression in a subset of prostate cancer patients.

As a result, PARPi have been approved for use in prostate cancer patients who have mutations in DNA repair genes.

HRR gene mutation

Homologous recombination repair (HRR) is a type of DNA repair that relies on several genes working together, the most well-known of which are BRCA1 and BRCA2.

In cancer cells, PARPi targets the DNA repair system and forces cells to use HRR. If there are mutations in the HRR genes, the HRR can’t function properly, and DNA can’t be accurately repaired. Eventually inaccurate DNA repair compromises the function of a cell, forcing the cell to induce cell death. Patients with mutations in HRR genes are therefore eligible for PARPi and genetic testing of the HRR genes is required.

HRR gene mutations aren’t only acquired to cancer cells but can also be inherited. Importantly, PARPi therapy is beneficial in patients with both inherited HRR mutations or acquired HRR mutations.

The recommended method for genetic testing of the HRR genes is known as next generation sequencing (NGS), which allows several HRR genes to be analysed simultaneously. NGS is used for the identification of inherited or acquired mutations, however, different samples are needed depending on the source of the mutation.

Germline vs somatic testing 

Germline testing refers to testing for inherited gene mutations that have implications to immediate family members. Genetic counselling is therefore required prior to germline testing to provide information about testing, what the possible results may be, and the implication of those results on immediate family members.

Conversely, somatic testing refers to testing for acquired mutations and uses the tumour tissue for genetic testing. On occasion, somatic testing can identify inherited mutations and germline testing may be recommended. A comparison between the types of tests is provided in Table 1.

Patients can be referred for germline or somatic testing or both based on certain criteria highlighted in clinical practice guidelines for prostate cancer.

Table 1: Germline and somatic testing for PARPi eligibility in prostate cancer.

Takeaway message

Genetic testing has become an important tool to identify the most effective treatment in prostate cancer and clinical management. Most private laboratories in SA offer genetic testing, using NGS for prostate cancer, as well as genetic counselling for patients requiring germline testing.

It’s important to highlight, however, that genetic testing isn’t always covered by medical funders and clinicians may be required to provide motivations for genetic testing.