Abstract 1197: Perineural invasion on prostate biopsy is associated with higher decipher genomic risk and adverse molecular features in localized prostate cancer.

Abstract Perineural invasion (PNI) in prostate cancer (PCa) needle biopsies is common, yet its prognostic value remains uncertain. Although associated with adverse pathology and disease progression, PNI is not integrated into current risk algorithms, and whether it reflects underlying aggressive tumor biology remains unclear. We aimed to assess the clinical and molecular relevance of PNI in localized PCa biopsies, and to examine its association with tumor features, clinical risk, and transcriptomic signatures of aggressiveness using the Decipher genomic classifier. We performed a retrospective analysis of men with localized prostate cancer who underwent transcriptomic profiling using the Decipher platform. PNI status was determined from pathology reports of diagnostic biopsies. Patients were stratified by Gleason Grade Group (GG1-GG3), NCCN risk category, and PAM50 molecular subtype. Decipher scores were classified as low (<0.45), intermediate (0.45-0.6), or high (>0.6). Associations between PNI and clinical and molecular features were evaluated using chi-square tests and subgroup stratification. Among 1,076 patients with GG1-GG3 disease, PNI was present in 20.5% of cases. Tumors with PNI were more likely to have higher Gleason grade and were overrepresented in the intermediate- and high-risk NCCN categories. Across GG1-GG3, PNI was strongly associated with higher Decipher genomic risk (64% vs. 31% in PNI-negative, p<0.001), and this association remained significant within GG1 and GG2 individually. In GG1, PNI correlated with increased luminal B PAM50 subtype prevalence, PTEN-loss, and TP53 mutation signatures, supporting its association with more adverse biology even in lower-grade cancers. Our study has shown that PNI on biopsy correlates with higher genomic risk and adverse clinical and molecular features, supporting its role as a marker of aggressive tumor biology. PNI may refine prognostic assessment, particularly in GG1-GG2 disease, and should be considered in risk-based decision-making pending prospective validation. Citation Format: Hagai Ligumsky, Tamar Zahavi, Yoav Manaster, Menahem Laufer. Perineural invasion on prostate biopsy is associated with higher decipher genomic risk and adverse molecular features in localized prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1197.