When To Consider a Re-Biopsy in the Metastatic CRPC Treatment Course

Many clinical characteristics may prompt a re-biopsy of hormone-resistant or castration-resistant prostate cancer (CRPC), according to Rahul Aggarwal, MD.

Following a presentation Aggarwal gave at the 19th Annual New York GU Cancers Congress®, he discussed findings from his presentation examining treatment-emergent neuroendocrine prostate cancer (t-NEPC), including considerations for biopsy in metastatic CRPC to gauge for the emergence of NEPC type disease, in a conversation with CancerNetwork®.

Noting that he will typically re-biopsy for any patient suspected of developing t-ENPC, he pointed to NCCN guidelines that recommend a metastatic biopsy for all hormone-resistant disease types among patients with an accessible lesion. Specifically, he expressed that beyond the potential presence of t-ENPC type disease, repeat biopsy could identify other characteristics, which prognostically signal more aggressive disease, including genomic alterations, microsatellite instability–high disease variants, and the loss of AR expression, for which t-NEPCs are a resistance mechanism.

Next, Aggarwal highlighted clinical “triggers” that could prompt a repeat biopsy, which included the presence of liver metastases, a history of RB1 mutation expression on prior genomic testing, as well as low prostate-specific antigen (PSA) scores, PSMA-PET–negative disease, and soft tissue disease. He concluded by suggesting that not all PET-negative lesions lead to uncovering t-NEPC type disease upon biopsy, but that neuroendocrine detection is enriched when doing it for these lesions.

Aggarwal is program leader of Genitourinary Medical Oncology and associate director for Clinical Research at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.

Transcript:

It’s this clinical gestalt of who we think is [developing t-ENPC]. That being said, NCCN guidelines recommend a metastatic biopsy in the hormone-resistant setting for all patients with an accessible lesion. We have to remember that there are other clinically actionable things we learn from that biopsy, including repeat genomic testing if it’s been done before or genomic testing for the first time, to look for a BRCA2 [mutation] or other associated alterations. Microsatellite [instability]–high [disease]––we see that in several patients. Then the histopathology, which we use to look at neuroendocrine [tumors], is one resistant feature. You can also have patients who may lose AR expression but also don’t have neuroendocrine markers, what we call double-negative phenotype, and we know that, prognostically, that’s also an indicator of more aggressive disease.

I would argue that there’s a lot of reasons to think about a metastatic biopsy for patients, which we do commonly in other disease types. That being said, yes, there are some clinical triggers where we’re going to try to push hard to do a biopsy. [For] any patient who has a liver metastasis, I’m going to think about a biopsy, regardless of what the PSA is or other clinical features. If a patient has a known RB1 mutation based on prior genomic testing, that’s going to be a scenario where I’ll make note that, yes, I want to get a biopsy on this patient at some point in their treatment course, ideally of a metastatic lesion, to look for neuroendocrine [disease]. Low PSA in relation to disease burden on imaging, PSMA-PET–negative, [and] soft tissue disease are sometimes triggers. Not all those patients [have neuroendocrine type disease], but you’re certainly enriching for neuroendocrine detection when you biopsy those PET-negative lesions. These are some of the clues that we might use in terms of guiding biopsy decisions.

Reference

Aggarwal R. Neuroendocrine prostate cancer: spectrum, recognition, and management implications. Presented at: 19th Annual New York GU Cancers Congress®; March 13-14, 2026; New York, NY.