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Risk of Prostate Cancer Recurrence Correlates With Number of Perineural Invasion Foci

Key findings

  • To investigate the link between perineural invasion (PNI) and outcomes in prostate cancer, Massachusetts General Hospital researchers counted the number of PNI foci in 721 radical prostatectomy specimens
  • All patients who later had metastasis progression were PNI+, and patients with more than three PNI foci had a significantly higher metastasis risk than those with fewer foci
  • The presence of more than three PNI foci was an independent risk factor for biochemical recurrence even when adjusted by Gleason score and the presence of positive surgical margins
  • Counting the number of PNI foci in surgical specimens should prove useful for risk stratification of patients with prostate cancer, and targeting PNI may someday prove to be an effective treatment approach

Perineural invasion (PNI)—a distinct route of cancer metastasis—is common in prostate cancer and refers to cancer surrounding or tracking along a nerve fiber. In some other types of cancer, PNI is associated with poor prognosis, but whether this is true in prostate cancer is controversial.

Most studies of PNI in prostate cancer have simply assessed whether it's present. Shulin Wu, MD, PhD, lab manager of the Urology and Pathology Research Laboratory at Massachusetts General Hospital, Chin-Lee Wu, MD, PhD, associate pathologist and director of Genitourinary Pathology Services at Mass General and the Mass General Cancer Center, and colleagues tried a novel method: counting the PNI foci in radical prostatectomy specimens. In Human Pathology, they report that a higher number of PNI foci correlates with an increased risk of biochemical recurrence (BCR).

PNI+ vs. PNI−

The researchers detected PNI in 530 of 721 surgical specimens (74%). Patients with PNI+ specimens were significantly more likely than those with PNI− specimens to have:

  • Gleason score (GS) ≥4+3—21% vs. 4%
  • pT3 stage—25% vs. 1%
  • Positive surgical margins (PSM)—28% vs. 6%

All these differences were statistically significant (P < .001).

BCR occurred in 19.4% of patients over a median follow-up of 8.5 years. PNI+ patients had a significantly higher BCR rate (24% vs. 6%, P < .001) and metastasis rate (5% vs. 0%, P = .001) than PNI− patients.

Focus Number

The number of PNI foci ranged from zero to 84, with a median of six. Based on univariate analysis, the researchers divided PNI+ patients into those with up to three foci and those with more than three.

Patients with more than three foci differed significantly from the other group in that they had a higher prostate-specific antigen level, higher grade, great likelihood of pT3 stage and greater frequency of PSM, BCR and metastasis.

Multivariate Analysis

PNI status (dichotomized yes/no) was not a significant independent risk factor for BCR when adjusted by GS and PSM. However, PNI+ with more than three foci was a prognostic factor (HR, 2.12; 95% CI, 1.02–4.40; P = .04).

Future Directions

Counting the number of PNI foci in surgical specimens should prove useful for risk stratification of patients with prostate cancer. This study further suggests that targeting PNI may someday prove to be an effective treatment approach.

74%
of prostate cancer patients had perineural invasion

5%
metastasis rate in prostate cancer patients with perineural invasion

0%
metastasis rate in prostate cancer patients without perineural invasion

2x
greater risk of biochemical recurrence in prostate cancer patients with >3 foci of perineural invasion compared to those with none

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