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

By: Claire M. de la Calle, MD; Mufaddal M. Mamawala, MBBS, MPH; Patricia Landis, BA; Katarzyna J. Macura, MD, PhD; Bruce J. Trock, PhD, MPH; Jonathan I. Epstein, MD; Christian P. Pavlovich, MD | Posted on: 17 Jan 2023

de la Calle CM, Mamawala MM, Landis P, et al. Clinical significance of perineural invasion in men with Grade Group 1 prostate cancer on active surveillance. J Urol. 2023;209(1):180-186.

Study Need and Importance

It is widely accepted that most men with Gleason grade (GG) group 1 prostate cancer can safely be monitored using active surveillance (AS). Yet, perineural invasion (PNI), a known mechanism of extracapsular spread, can coexist with GG1 prostate cancer. The clinical significance of finding PNI on biopsy in men with GG1 disease on AS is unclear. In this study we aimed to assess the association between PNI and grade reclassification (GR) during AS and its association with oncologic outcomes after radical prostatectomy.

What We Found

We identified 198 men with GG1 prostate cancer and biopsy-detected PNI at any time point during AS. We found that men with PNI experienced earlier GR and that PNI was significantly associated with GR (see Table). The subset of men with PNI that ultimately underwent radical prostatectomy exhibited more extraprostatic extension. Yet, PNI detected on biopsy during AS was not associated with other features of adverse pathology, and these patients did not experience more biochemical recurrence (BCR).

Table. Multivariable Regression Model for Grade Reclassification in the Overall Cohort (N=1,969)

Covariate Hazard ratio 95% CI P value
Perineural invasion (present vs absent) 3.25 2.54-4.16 < .001
Year of diagnosis 1.09 1.07-1.11 < .001
Age (per year increase) 1.05 1.03-1.06 < .001
PSA density (per 0.1 unit increase) 1.30 1.14-1.47 < .001
No. positive cores 1.19 1.12-1.27 .03
Maximum percent core involvement 1.00 0.99-1.00 .70
Abbreviations: CI, confidence interval; PSA, prostate specific antigen.
Bold indicates statistical significance.


This is a retrospective study limited by heterogeneity in the patient cohort, reflective of the evolution of AS protocols over time at our institution. This is, for example, reflected in the absence of magnetic resonance imaging of the prostate in a large portion of the cohort. Similarly, there was not a set protocol to guide transition to active treatment. Finally, the event rate for BCR was overall very low so the clinical significance of the BCR findings is unclear.

Interpretation for Patient Care

This study supports active surveillance for GG1 patients with PNI, as PNI did not confer a higher risk of adverse oncologic outcomes after radical prostatectomy in our cohort (other than extraprostatic extension). PNI was, however, associated with GR, suggesting that men with PNI on AS may benefit from closer surveillance.