A novel application of Decipher testing in HoLEP specimens for risk stratification of incidentally detected prostate cancer.

Objectives: To assess the feasibility of Decipher testing for prostate cancer incidentally identified on specimens from holmium laser enucleation of the prostate (HoLEP). Additionally, we sought to review Decipher GRID expression signatures in cancers identified on HoLEP compared to those identified on prostate biopsy.

Methods: We identified patients who had prostate cancer on HoLEP at our institution from August 2021-July 2024 and subsequently underwent Decipher testing. Quality assurance testing was performed and transcriptomic signature expression patterns between HoLEP specimens and Grade Group (GG)-matched biopsy specimens were compared using standard mean differences (SMD).

Results: Of the 38 HoLEP specimens that underwent Decipher testing, 2 (5.3%) failed quality assurance testing due to lack of sufficient tumor present in the sample. Compared to GG-matched biopsy specimens (N=58,500), the HoLEP group (N=36) had similar median Decipher scores (0.56 vs 0.45, SMD 0.33) and lower median PSA (3.1 vs 6.2). HoLEP specimens were enriched for lower androgen receptor activity (SMD 0.63), basal subtypes by both PAM50 (SMD 1.23) and PSC (SMD 1.09), and ERG negative status (SMD 0.86). HoLEP specimens also had higher expression of activated CD4 (SMD 1.06), tertiary lymphoid structure (SMD 1.40), and angiogenesis (SMD 1.27).

Conclusion: Decipher testing for HoLEP specimens is feasible, although clinical utility remains unclear. Compared to biopsy specimens, HoLEP specimens have increased immune and angiogenesis-related signature expression and lower AR-A expression suggesting that these tumors have unique microenvironments.