Objectives: To assess the prognostic effect of perineural invasion (PNI) for patients undergoing external beam radiotherapy for prostate cancer. Methods: We evaluated 657 consecutive patients who had undergone external beam radiotherapy for clinically localized prostate cancer. The clinical/treatment parameters used for analysis included PNI, clinical stage, biopsy Gleason score, pretreatment prostate-specific antigen, radiation dose, and androgen deprivation. The primary endpoint was biochemical recurrence defined by the Radiation Therapy Oncology Group-American Society for Therapeutic Radiology Oncology Phoenix consensus; the secondary endpoint was prostate cancer death. Results: Of 586 men with a minimum of 24 months of follow-up, 112 (19.1%) had PNI present in the biopsy specimen. When patients were stratified into risk groups using the National Comprehensive Cancer Network criteria, PNI was more prevalent in patients within higher risk groups (6.8% in low-risk versus 18.3% in intermediate-risk versus 30.1% in high-risk groups; P <0.001). The presence of PNI was associated with lower biochemical recurrence-free (P = 0.003) and cancer-specific (P = 0.040) survival rates by Kaplan-Meier analysis. Cox regression analysis showed that PNI was a statistically significant prognostic factor of biochemical recurrence on both univariate (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.19 to 2.46, P = 0.004) and multivariate (HR 1.57, 95% CI 1.06 to 2.32, P = 0.025) analyses. Regression analysis after stratification by risk group and adjustment for treatment covariates demonstrated a significant association between PNI and the risk of biochemical recurrence for low-risk (HR 4.14, 95% CI 1.55 to 11.02, P = 0.005) and intermediate/high-risk patients (HR 1.53, 95% CI 1.02 to 2.29, P = 0.040). Conclusions: The results of our study have shown that the presence of PNI is an independent risk factor associated with an increased risk of biochemical recurrence in patients with prostate cancer undergoing external beam radiotherapy.
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