This transcript has been edited for clarity.
Hello. I’m Dr Maurie Markman, from City of Hope. I’d like to discuss a very interesting and controversial topic. The paper I’m discussing is “Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study,” published in the Journal of Urology.
It has been well recognized for over a decade that patients with ovarian cancer need to have germline testing, independent of whether they have a family history of that particular cancer because we identified particular mutations — BRCA mutations, BRCA1 and BRCA2 — that may not be evident in the family by history but are very relevantpotentially for cascade testing of their family members later. Also, of course, in that setting, there are therapeutic implications for the use of PARP inhibitors.
Increasingly, the discussion is about more universal testing for patients with breast cancer because of the incidences of BRCA and other mutations that are both relevant for treatment and for the question of genetic counseling for other members of the family.
What about other tumor types? What about genitourinary (GU) cancers, as identified here? Should one take patients with all different kinds of GU tumors — prostate cancer, bladder cancer, kidney cancers, typically — and say there’s a role for universal germline testing when a patient has been identified as having one of these cancers?
To address this question, the group at the Mayo Clinic undertook comprehensive germline testing, examining for pathogenic germline variants at several sites from April 2018 to March 2020. This was a greater than 80-gene panel that was offered to patients. Today, that testing may be really quite different, but at that point it was greater than 80 genes that were tested for potential abnormality.
A total of 601 patients enrolled with GU cancers. Again, this was across the sites and with GU cancers, regardless of a family history. There were 358 patients with prostate cancer, 106 with bladder cancer, and 137 with kidney cancer. Surprisingly, a majority of these patients, 86%, were male.
Here is the important bottom line. Pathogenic germline variants, most with risk of high penetrance, were identified in 82 individuals, or 14% of the population. First, they were seen in almost the same percentage in kidney, bladder, and prostate cancer, and that 14% is not that far off. In fact, it’s quite similar to the statement about ovarian cancer in terms of the overall population — 14% of the patients with GU cancer.
Importantly, at this time, based on these data, fully 67% (or 2 of 3) patients had abnormalities that were potentially actionable. “Actionable” could mean a variety of things. It could mean there may be a therapy involved. It could mean that we need to talk to members of the family. They were not like, “Oh, that’s interesting, but there’s nothing we can do about it.” For 2 out of 3, they could actually do something actionable.
Importantly, of those 82 patients, 35% had at least one relative undergo cascade testing to examine for that variant.
The bottom line here is that more than 1 of 8 patients in this unselected group of patients with GU cancers had a variant finding that was potentially pathogenic at the germline level. This would argue for — although there is going to be controversy and we need more data — universal testing, certainly of GU tumors, and one might ask for other tumor types.
We need more data to confirm that. This would obviously be an extensive, new universal recommendation with costs associated with it, but this paper certainly raises that question that needs to be further examined.
Thank you for your attention.