Quantification of perineural invasion on prostate biopsy improves risk stratification in biopsy Grade Group 2–3 cancer

Abstract Objective Perineural invasion (PNI) detected on prostate needle biopsy is a well‐established indicator of adverse pathology, while the prognostic role of PNI quantification has recently been suggested. We herein aimed to determine whether PNI quantification could universally stratify risks by separately assessing subgroups of patients based on biopsy Grade Group (GG). Methods We quantified actual PNI foci in the entire systematic sextant biopsy specimens from 840 men, including 580 (69.0%) exhibiting no PNI and evaluated long‐term oncologic outcomes following radical prostatectomy. Results PNI was detected in 1 (n = 177; 21.1%), 2 (n = 48; 5.7%) or 3–6 (n = 35; 4.2%) of 6 biopsy sites/parts, while 1 (n = 156; 18.6%), 2 (n = 53; 6.3%) or 3–10 (n = 51; 6.1%) PNI foci were present on each biopsy. In the entire cohort, we confirmed a significantly higher risk of biochemical recurrence in patients with PNI (vs. no PNI; P < 0.001), multi‐site PNI (vs. single‐site PNI; P < 0.001) or multifocal PNI (vs. unifocal PNI; P < 0.001). In subgroup analyses, significant differences in the risk of postoperative recurrence between the absence vs. presence of PNI were observed only in patients with GG3 or GG4 cancer. In contrast, the prognostic distinction between single‐site vs. multi‐site PNI or unifocal vs. multifocal PNI was evident in patients with GG2 or GG3 cancer, but not in those with GG1 or GG4–5 cancer. In multivariable analysis, multifocal PNI, but not multi‐site PNI, was independently associated with worse recurrence‐free survival in the GG2 (hazard ratio 5.866, P = 0.004) and GG3 (hazard ratio 2.716, P = 0.021) groups. Meanwhile, PNI on prostatectomy was confirmed in 98.1% of biopsy PNI‐positive cases but was still detected in 72.2% of biopsy PNI‐negative cases. Conclusion Quantification of actual PNI foci across all systematic biopsy sites may provide valuable prognostic information, particularly in patients with GG2–3 cancer. Notably, the mere presence of biopsy PNI may not universally predict poorer outcomes.