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Clinical Significance of Perineural Invasion in Men With Grade Group 1 Prostate Cancer on Active Surveillance

Purpose: We aimed to evaluate the clinical significance of perineural invasion in men on active surveillance for Grade Group 1 prostate cancer. Materials and Methods: We identified 1,969 men with Grade Group 1 prostate cancer and at least 1 follow-up biopsy. A time-dependent Cox model and a logistic regression model were used to assess the association between biopsy-detected perineural invasion and grade reclassification (defined as the detection of Grade Group ≥2 prostate cancer on a surveillance biopsy), and adverse pathology (defined as Grade Group ≥3 ± seminal vesicle invasion ± lymph node involvement) at radical prostatectomy, respectively. Results: The 198 men with perineural invasion detected during active surveillance had lower rates of grade reclassification-free survival than those without perineural invasion (P < .001). On multivariable analysis perineural invasion was significantly associated with grade reclassification (HR 3.25, 95% CI 2.54-4.16, P < .001); an association that persisted in the multiparametric magnetic resonance imaging subset. At radical prostatectomy, men with biopsy-detected perineural invasion had more extraprostatic extension than men without perineural invasion (Relative Risk 1.71, 95% CI 1.15-2.56). However, on multivariable analysis biopsy-detected perineural invasion was not associated with adverse pathology (OR 0.68, 95% CI 0.27-1.68, P = .40) and these patients did not exhibit more biochemical recurrence at 5 years (P > .05). Conclusions: Perineural invasion during active surveillance was associated with grade reclassification. At radical prostatectomy biopsy-detected perineural invasion patients exhibited more extraprostatic extension but biopsy-detected perineural invasion was not independently associated with more adverse pathology. In addition, these patients did not have more biochemical recurrence during follow-up. Perineural invasion should not preclude Grade Group 1 patients from active surveillance but they may warrant more stringent monitoring.