Half of US prostate cancer patients with inherited risk genes missed

US men with prostate cancer could be missing out on targeted treatments because they do not meet the current guidelines for genetic testing.

Knowing if a patient has inherited genetic variants that increase cancer risk can help doctors prescribe the best treatment. Current US National Comprehensive Cancer Network (NCCN) guidelines only recommend germline genetic testing (GGT) for high-risk, very high-risk, regional, or metastatic prostate cancer, as well as those with a family history of some cancers or with Ashkenazi Jewish heritage.

'We found no statistically significant difference in the diagnostic yield of [pathogenic germline variants] PGVs between those who met NCCN guidelines and those who did not, suggesting there are a significant number of patients with PGVs, many of which are targets for precision therapies, who are being missed', said lead author Dr Neal Shore, from the Carolina Urologic Research Centre in Myrtle Beach, South Carolina.

The researchers recruited 958 men with low- or intermediate-risk prostate cancer who had not previously had germline genetic testing. Around half (51 percent) met the NCCN guidelines, while the rest did not. All the men received screening for 84 pathogenic or likely-pathogenic germline variants known to give a predisposition to cancer.

The results, published in the European Urology Oncology, identified 77 PGVs across 17 genes, affecting 7.7 percent of the participants. Furthermore, the majority (81 percent) of the PGVs were 'clinically actionable', meaning that the patients with those variants could benefit from targeted therapies such as PARP inhibitors, or be eligible to take part in clinical trials.

The study results showed that white men had, on average, more PGVs than other groups. However, black men who did not meet NNC criteria actually had a greater number of PGVs than those who did. This suggests the guidelines may disproportionately disadvantage black men, who are already at greater risk of prostate cancer and more aggressive forms of the disease.

'These data support that comprehensive GGT should be offered to all [prostate cancer] patients in order to identify actionable PGVs,' the authors concluded.