Sofie Tolmeijer: Yeah. Thank you so much for having me.
Neeraj Agarwal: Sofie, first of all, congratulations for presenting such an impactful study at the ASCO GU 2026 meeting as a postdoc fellow in one of the top institutions, Vancouver Cancer Center, and working with Dr. Alexander Wyatt, another legend in the field. And it's amazing to see how much you have done so early in your career.
Sofie Tolmeijer: Yeah. Thank you so much for your compliments.
Neeraj Agarwal: So, let's talk about the data you are presenting at the ASCO GU meeting. 3,000-plus patients, data collected over 10 years, humongous amount of effort, and you looked at germline testing results of these patients with metastatic prostate cancer. Please tell us more about the results.
Sofie Tolmeijer: Yeah. Yeah. Thank you so much for the introduction as well. So we think inherited variants are very important for prostate cancer, and especially those in DNA damage repair genes. However, the full spectrum, especially at metastatic disease is not fully known, and also the type of variants that you see in these DNA damage repair genes. So what we now did is we looked in 3,005 patients with metastatic prostate cancer. In an assay that we do at the Vancouver Prostate Center in collaboration with BC cancer to investigate 31 DNA damage repair genes and look at what type of inherited variants do we find, both very small variants and very large variants. And I think unexpectedly, we saw 9% of patients carry variants in such a DNA damage repair gene in their germline with BRCA2, ATM, and CHEK2 being the most prominently altered genes. But there's also a whole variety of more rare alterations. Examples are PALB2, MSH2, MSH6, but even CDK12, which we presented on at last ESMO. The type of variants is also very different in these genes, and they can be very small, they can be truncating variants, but we also saw that approximately 4% of these variants are these large structural variants that are often missed by current assessment methods. So I think those are very important to address as well in the future.
Neeraj Agarwal: Metastatic prostate cancer being so common and 4% of this common disease is a very large number of patients out there.
Sofie Tolmeijer: Yes.
Neeraj Agarwal: Based on the results you got, it looks like there is a potential for currently available CLIA-certified testing platforms to miss those mutations. Did I get it correctly?
Sofie Tolmeijer: Yeah. So I think they're currently maybe not reporting on them or missing them. So I think there should be definitely a further investigation if they are missed in current practice. And that is actually for your germline testing, but maybe also for your somatic testing, because we saw different types of variants, again, in your somatic second allele that is inactivated in some of these patients. They can also be structural variants, these larger variants. They can be loss of heterozygosity. There can be point mutations. And depending on which genes you are interested in and you want to evaluate, you might want to adjust your testing strategy.
Neeraj Agarwal: Very good point. So again, just want to summarize for our worldwide audience that about 10% of these patients have these germline pathogenic variants in the metastatic prostate cancer setting in DNA damage repair genes.
Sofie Tolmeijer: Yes.
Neeraj Agarwal: And 4% of them have such large ones which may be missed by the current commercial testing platforms.
Sofie Tolmeijer: Yes.
Neeraj Agarwal: What is your message for our patients, physicians, clinicians who are ordering this test right now and they're getting the results from these CLIA-certified testing platforms, what they should be paying attention to?
Sofie Tolmeijer: Yeah, I think that's a very important question. So I think we have to pay attention to what does your test report? Are they reporting these large variants? Are they not reporting these large variants? Which genes do they report? Are they missing maybe potential genes of interest that can be rarely altered but still impactful for patients? So when deciding on doing such a test and also when there's maybe a suspicion of an inherited variant because it's common in the family, for example, we might consider doing a further investigation for those patients in particular to find these variants that may be more rare, but still very clinically relevant.
Neeraj Agarwal: And many of these patients are primarily seen by genetic counselors because clinicians refer those patients to those genetic counselors and they're very smart people, but they're also using CLIA-certified platforms. They're not using the platform you used. It's a much deeper sequencing if I understood correctly. Any message for the genetic counselors?
Sofie Tolmeijer: Think about what the test is reporting basically. Think about what might be the limitations. I think genomic and genetics is a continuously evolving field and we're discovering new things every day. And personally, I think our test is still missing some variants which might be detected with a new generation of assays. So my most important message would be consider the flaws of your assay and the promises of your assay and be able to discuss those among each other, among professionals of what might be missed and what we should look for.
Neeraj Agarwal: What are the future plans for commercialization? I'm not asking for any confidential plans, but do you think this testing, a much deeper testing platform would be available anytime soon to our patients?
Sofie Tolmeijer: I know that a lot of more whole-genome sequencing is, for example, performed, much more whole-exome sequencing is performed because sequencing gets more affordable. And I think that's very promising also for genetic testing with these large variants that might be missed by small targeted assays. So I actually look forward to seeing much more of these whole-genome approaches and what type of variants they might identify that we've missed in the past.
Neeraj Agarwal: Any concluding message for our community out there who's taking care of these patients?
Sofie Tolmeijer: My final conclusion would be take into consideration which genes you are interested in, which type of variants you expect, and also which type of variants you might miss with the assay that you're using. And I look forward to all the developments that happen in the genetic fields at the moment.
Neeraj Agarwal: And I'll reinforce that message with another message, that every patient with advanced or metastatic prostate cancer patient should undergo germline testing because that can have implications, not only on their own care, but on their families, their daughters, their sons, their siblings, sisters, and brothers. And I think we ought to do a better job because still only a minority of patients with metastatic prostate cancer are undergoing germline testing.
Sofie Tolmeijer: Yeah. Thank you so much for adding that because I think that's maybe the most important thing that we should focus on is getting access to patients to do genetic testing and to investigate are these variants there and what are the implications both clinically for themselves, therapeutic targets that might be there, but also for their family members and their risk of developing different types of cancer. So thank you very much for adding that.
Neeraj Agarwal: Thanks, Sofie, for spending time with us to share your results. Congratulations again and congratulations to Dr. Alex Wyatt, your mentor. And again, congratulations.
Sofie Tolmeijer: Thank you so much for having me.