Clinical impact of perineural cancer invasion detected in prostate cores: Involvement of spatially contiguous versus separate biopsy sites.

To the Editor, The presence of perineural invasion (PNI) by prostate cancer, particularly on biopsy, has been associated with adverse pathology, including extra‐prostatic extension as the suggested main route of cancer spread out of the prostate. Recently, we have additionally found that PNI in multiple biopsy sites (vs. single site) or both right and left biopsy sites (vs. two unilateral sites) is an independent prognosticator in prostate cancer patients undergoing radical prostatectomy. The present study aimed to further determine the clinical significance of biopsy PNI detected in potentially contiguous versus separate lesion(s). In one of our previous studies, we assessed radical prostatectomy findings and postoperative oncologic outcomes in men with prostate cancer exhibiting PNI in only two of the sextant biopsy sites (i.e., right apex, right mid, right base, left apex, left mid, left base). We then compared unilateral (n = 140; two of either right or left sites) versus bilateral (n = 30; one of right sites and one of left sites) PNI cohorts and found that bilateral PNI was strongly associated with a poorer prognosis, but not worse histopathologic features on biopsy or prostatectomy. We herein used the same cohort of these 170 patients. Data were analyzed, using the Student's t test for continuous variables, as well as the χ test or Fisher's exact test for noncontinuous variables. Progression‐free survival was assessed by the Kaplan–Meier method and the Gehan–Breslow–Wilcoxon test, while disease progression was separately defined as a single prostate‐ specific antigen (PSA) level of ≥0.2 ng/mL or the introduction of adjuvant therapy in patients with no adjuvant therapy immediately after prostatectomy (n = 125) and as an increase in PSA value of ≥2 ng/mL or the introduction of salvage therapy in those undergoing immediate adjuvant therapy (n = 45). In addition, the Cox proportional hazards model was used to determine statistical significance of prognostic factors in a multivariable setting. A p‐value of <0.05 was considered to be statistically significant. We thus retrospectively examined 170 sets of prostate biopsy showing PNI in two of six sites and corresponding radical prostatectomy. These did not include any cases exhibiting PNI on targeted biopsy or undergoing neoadjuvant therapy prior to prostatectomy. PNI was identified at spatially contiguous or separate site(s) (see Figure 1a) in 114 (67.1%) or 56 (33.9%) cases, respectively. Surgical margin was significantly (p =0.020) more often positive in the separate group (35.7%) than in the contiguous group (19.3%) (Supporting Information: Table S1). However, no significant differences were observed in other clinicopathologic features examined, including age at biopsy (p= 0.208), preoperative PSA (p= 0.434), number of cancer‐positive biopsy sites (p =0.325), Grade Group on biopsy (p= 0.765) or prostatectomy (p= 0.500), pT stage (p= 0.680), pN stage (p= 0.303), estimated tumor volume (p= 0.076), and the need for adjuvant therapy immediately after prostatectomy (p=0.663). When these clinicopathologic features were compared separately in patients with unilateral (contiguous: n = 101 (72.1%); separate: n= 39 (27.9%); Supporting Information: Table S2) or bilateral (contiguous: n= 13 (43.3%); separate: n =17 (56.7%); Supporting Information: Table S3) PNI, there were no significant differences between contiguous versus separate cohorts. Univariable analysis was then performed to compare the progression‐free survival following radical prostatectomy between patients with spatially contiguous and separate PNI. In the entire cohort, the separate group had a significantly higher risk of disease progression than the contiguous group (p = 0.023; Figure 1b). Interestingly, the significant difference in progression‐free survival between contiguous versus separate cohorts was observed in those with bilateral PNI (p = 0.044; Figure 1d), but not unilateral PNI (p = 0.801; Figure 1c). In addition, the risk of progression in the 17 patients with bilateral/ separate PNI was significantly higher than that in those with unilateral (n = 140) or bilateral/contiguous (n = 13)