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 Congressยฎ, 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 CancerNetworkยฎ.
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 instabilityโhigh disease variants, and the loss of AR expression, for which t-NEPCs are a resistance mechanism.
Next, Aggarwal highlighted clinical โtriggersโ 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-PETโnegative 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:
Itโs 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 itโs been done before or genomic testing for the first time, to look for a BRCA2 [mutation] or other associated alterations. Microsatellite [instability]โhigh [disease]โโwe 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 donโt have neuroendocrine markers, what we call double-negative phenotype, and we know that, prognostically, thatโs also an indicator of more aggressive disease.
I would argue that thereโs 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 weโre going to try to push hard to do a biopsy. [For] any patient who has a liver metastasis, Iโm 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, thatโs going to be a scenario where Iโll 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-PETโnegative, [and] soft tissue disease are sometimes triggers. Not all those patients [have neuroendocrine type disease], but youโre 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 Congressยฎ; March 13-14, 2026; New York, NY.
