Many pathogenic germline variants in GU cancers would be missed according to current guidelines

In this video, Mouneeb Choudry, MD, and Adri Durant, MD, describe the background and notable findings from the Journal of Urology study “Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study.” Choudry and Durant are urology residents at Mayo Clinic in Phoenix, Arizona.

Transcription:

Please describe the background for this study.

Choudry: We wanted to look at the importance of genetic testing in patients with GU cancer and the impact that it has on their treatment decision-making, and the pathways that we put them on. The identification of germline testing, it's affected patients, and it really has important implications in that treatment decisions and their risk of producing future interventions, and cancer screening in general and also the relevance it has in terms of their relatives and the impact it has on their family members. And in recent years, there's been more of a emphasis or concern that's been placed on finding more targeted therapies for individuals with advanced cancers, particularly if you look at patients with prostate cancer, and you look at patients who have metastatic prostate cancer and the use of the PARP inhibitors. And with the FDA recently approving that, there was more of a concern and more of a need, we felt, to better identify the use of universal genetic testing in the GU cancer population. The only other study that really looked at this before was PROCLAIM trial. That was one of the first times where we really looked at comparing universal genetic testing vs just following the guideline-based genetic testing for patients. With all that, and the recent need for a better understanding of the usefulness of genetic testing, that's the reason why we wanted to dive deep into this idea and get some better answers.

What were some of the notable findings? Were any of them surprising to you and your coauthors?

Durant: This was a multi-site study involving Mayo Clinic institutions across the country, and over 600 patients with GU cancers were enrolled. This included patients with prostate, kidney and bladder cancer. Universal genetic testing was offered to them regardless of guideline recommendations. And when we looked at the pathogenic variants identified, we found that overall, nearly 15% of patients had pathogenic variants that were represented on the genetic testing, which was pretty notable. And then when we looked at these pathogenic variants, actually, two thirds of those patients went on to have clinically impactful changes, whether that's increased screening or surveillance. And then when we looked at cascade testing, or whether their families went on to have changes in their care based on that, nearly a third of those patients went on to have family tested based on these results. And then another, I think, really probably the most notable finding of this was the incremental findings of the test. And that means that patients who were identified to have pathogenic variants who would not have been identified based on current guidelines. We identified a very high percentage within this population. And so of patients with bladder cancer, 100% of the pathogenic variants would have been missed based on current guidelines. In kidney cancer, 80% of patients almost would have been missed based on current guidelines, and over 50% of the patients with prostate cancer with pathogenic variants would have been missed based on current guidelines. And so I think that was really the shocking thing that we found and the really clinically impactful thing that came out of this study

This transcription was edited for clarity.