Recent research highlights the significance of universal germline genetic testing (GGT) in uncovering pathogenic germline variants (PGVs) across various genitourinary (GU) malignancies. A study conducted at Mayo Clinic, Minnesota, USA, from April 2018 to March 2020 examined the prevalence of PGVs in patients with prostate, bladder, and renal cancers, revealing that over one in eight patients carried these critical genetic alterations. This research underscores the potential shortcomings of current testing guidelines and supports a broader approach to genetic screening in urologic oncology.
The study involved 3095 participants, with 601 diagnosed with GU cancers (358 prostate, 106 bladder, and 137 renal). All participants underwent GGT using a comprehensive next-generation sequencing panel covering over 80 genes. The results showed that 82 patients (14%) had PGVs, distributed as 14% in prostate cancer, 14% in bladder cancer, and 13% in renal cancer. Notably, nearly one-third of these PGVs were high-penetrance, with 67% of these cases resulting in clinically actionable findings.
A key insight from this study was the identification of PGVs that would have been missed under the National Comprehensive Cancer Network (NCCN) guidelines. Specifically, 57% of prostate cancer patients, 100% of bladder cancer patients, and 78% of renal cancer patients had PGVs not captured by current guidelines. This finding emphasises the limitations of existing criteria, which are typically based on specific pathological features, age, or family history.
The study also highlighted the importance of cascade testing, with 35% of PGV-positive patients having at least one relative who underwent follow-up genetic testing. Overall, the research advocates for the adoption of universal GGT in GU cancers, challenging traditional guidelines and suggesting that a more inclusive testing approach could enhance patient care and outcomes. Future studies should further explore the cost-effectiveness and long-term impact of broad-based genetic screening, as well as address the psychosocial aspects of genetic testing for patients and their families.
Katie Wright, EMJ
Reference
Choudry MM et al. Germline pathogenic variants identified in patients with genitourinary malignancies undergoing universal testing: a multisite single-institution prospective study. J Urol. 2024;212(4):590-599.
