Alicia K. Morgans, MD, MPH: Sandy made a comment on this previously. Scott, before we move on to some imaging-based biomarkers, I want to hear your thoughts on how you’re testing for somatic mutations in particular. Because as Sandy mentioned, many of our patients have bone metastases. Not as many have accessible lymph node or visceral metastases that we can easily biopsy and sequence. What are your thoughts about bone metastases and tissue biopsies vs using prostatectomy specimens vs using liquid biopsies, which are available but not always concordant with our tissue samples?

Scott T. Tagawa, MD, MS, FACP: Optimally, for any given patient, it’s best to use a plethora of different tools. On a practical basis, I agree that getting a tissue-based biopsy at any given time is often the most invasive and difficult. There’s a fairly large percentage of patients, at least by standard imaging, who have bone-only metastasis. That being said, we can get information. About 5 years ago, we published our bone biopsy series, and I believe 85% of the bone biopsies were diagnostic, with 82% able to do whole-exome sequencing and a little less in terms of RNA-seq [RNA sequencing]. So it’s possible.

The caveat is the patients who we thought we probably couldn’t do, like those with a very small rib metastasis, for instance. But that being said, it’s possible. And at least as of today, we get the most depth of analysis from a tissue biopsy. But as I tell patients—you mentioned heterogeneity—we get a great depth of whatever is in the needle, and that’s it. The same tumor in a different location may be a little different. That’s where I think of the addition of blood-based biomarkers, which are clearly the easiest in my mind, as long as someone doesn’t have a hematological malignancy for germline.

I would clarify circulating tumor DNA a little differently than cell-free DNA. Circulating tumor DNA, where we have a germline-matched sample, is very good. It’s not as sensitive, but we can really trust those results. When we have cell-free DNA without a germline sample, we have to worry about clonal hematopoiesis. Just a thought. But we want to take every test into context and at least give prognostic information, which will help guide treatment choices, but also, particularly in the setting of different therapeutic interventions, it can probably give some predictive information to a subset. That subset is 0 if you don’t test.

Alicia K. Morgans, MD, MPH: I couldn’t agree more. And to emphasize that there can be challenges with those cell-free DNA assays having CHIP, or clonal hematopoiesis of indeterminate potential, particularly on genes like ATM, it’s so important to make sure you can match with a germline sample. All patients with advanced prostate cancer, high-risk localized or metastatic hormone-sensitive and beyond, are eligible for germline testing at this point in time. They’re not just eligible, it’s recommended. Thank you for clarifying that.

Transcript Edited for Clarity